@article {pmid42015439,
year = {2026},
author = {Rafique, B and Arshad, AR and Sabir, S and Ijaz, U and Rahman, OU},
title = {N-acetylcysteine as Prophylaxis Against Contrast-Induced Nephropathy: A Meta-Analysis.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {36},
number = {4},
pages = {508-519},
doi = {10.29271/jcpsp.2026.04.508},
pmid = {42015439},
issn = {1681-7168},
mesh = {Humans ; *Acetylcysteine/therapeutic use/administration & dosage ; *Contrast Media/adverse effects ; *Acute Kidney Injury/chemically induced/prevention & control ; Renal Dialysis ; Administration, Oral ; Incidence ; },
abstract = {This study aimed to determine the effect of N-acetylcysteine (NAC) in preventing contrast-induced nephropathy. A literature search was carried out in PubMed and Cochrane CENTRAL, and 49 studies were finally included. With oral NAC, there was no difference in the incidence of acute kidney injury (AKI; OR: 1.00; 95% CI: 0.90- 1.11; p = 0.98), the need for haemodialysis (HD; OR: 0.94; 95% CI: 0.61- 1.46; p = 0.79), or mortality (OR: 1.08; 95% CI: 0.83- 1.41; p = 0.55). The results were not affected during subgroup analysis for low- or high-dose oral NAC. With intravenous (IV) NAC, there was no difference in the incidence of AKI (OR: 0.84; 95% CI: 0.67- 1.04; p = 0.19), the need for HD (OR: 0.74; 95% CI: 0.19- 2.86; p = 0.66), or mortality (OR: 1.11; 95% CI: 0.67- 1.85; p = 0.68). Neither oral nor IV NAC decreases the risk of contrast-induced nephropathy. Key Words: Acetylcysteine, Acute kidney injury, Mortality, Renal dialysis.},
}

Humans
*Acetylcysteine/therapeutic use/administration & dosage
*Contrast Media/adverse effects
*Acute Kidney Injury/chemically induced/prevention & control
Renal Dialysis
Administration, Oral
Incidence

@article {pmid42020841,
year = {2026},
author = {Kumar, A and Bhaskar, M and Rani, R},
title = {Synergistic mitigation of lead [Pb(II)] stress in Triticum aestivum L. by heavy metal-tolerant plant growth-promoting (HMT-PGP) microbes and N-acetylcysteine (NAC).},
journal = {Plant cell reports},
volume = {45},
number = {5},
pages = {},
pmid = {42020841},
issn = {1432-203X},
abstract = {Synergistic application of N-acetylcysteine (NAC) and heavy metal-tolerant plant growth promoting (HMT-PGP)microbial consortia enhances Pb(II) phytostabilization and stress tolerance in Triticum aestivum L. by improvinggrowth, redox balance, and limiting metal uptake. This study emphasizes a synergistic approach using N-acetylcysteine (NAC) and heavy metal-tolerant plant growth-promoting (HMT-PGP) microbes to enhance lead [Pb(II)] phytostabilization in Triticum aestivum L. under hydroponic conditions. Though microbial consortia (MC) and NAC individually improved seed germination and viability, along with physiological and biochemical parameters under Pb(II) stress, the effects were more pronounced in the combined treatment (MC and NAC). In the combined treatment, seed germination, viability, amylase, and protease activities were found to increase by 20.7, 27.7, 21.4, and 10.82%, respectively, compared to the Pb(II)-stressed control (T1). Furthermore, combined treatment (NAC + MC) enhanced plant root, shoot length, biomass, and total chlorophyll by 46.9, 34.1, 21.6, and 45.6%, respectively, while total carotenoids and chlorophyll-carotenoid ratio decreased by 14.1 and 43.8%, respectively. Treatment with MC and NAC protected the plants against Pb(II) toxicity, as evidenced by significant declines in oxidative stress markers (hydrogen peroxide, malondialdehyde, proline) and in antioxidant enzyme activity. MC and NAC, individually and synergistically, restricted the Pb(II) uptake and accumulation in plants, thus leading to a significant reduction in bioconcentration (BCF) and translocation factor (TF) values. The BCF values for Pb(II) in the plants were 0.74 (untreated), 0.61 (MC), 0.67(NAC), and 0.58 (MC + NAC); while those for TF were 0.16, 0.11, 0.12, and 0.095, respectively. The treatments also promoted colonization of root endophytes. The findings suggest that MC and NAC, independently and synergistically, not only maintain redox homeostasis but also restrict Pb(II) entry in the plant. Therefore, it offers a novel approach for enhancing T. aestivum tolerance to Pb(II)-induced stress, promising avenues for sustainable agricultural practices and environmental remediation.},
}

@article {pmid41814419,
year = {2026},
author = {Chen, Y and Zhang, X and Pang, X and Yang, Y and Lu, D and Zhao, J and Zhu, J and Du, W and Gu, C and Li, J and Gu, L and Huang, JA and Liu, Z and Zeng, Y},
title = {SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41814419},
issn = {1479-5876},
support = {82272648//the National Natural Science Foundation of China/ ; 82202886//the National Natural Science Foundation of China/ ; SKY2022133//the Science and Technology Plan Project of Suzhou/ ; SKY2023160//the Science and Technology Plan Project of Suzhou/ ; GSWS2021001//Suzhou Gusu Medical Youth Talent/ ; ZDXK202201//Jiangsu Provincial Medical Key Discipline/ ; },
abstract = {BACKGROUND: Mitochondrial dysfunction has been implicated in various cancers, including non-small cell lung cancer (NSCLC). This study aimed to elucidate the role of mitochondrial dysfunction in NSCLC prognosis and the molecular mechanisms involved, particularly focusing on the Serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in mitochondrial metabolism.

METHODS: We analyzed the expression of SHMT2 in NSCLC tissue and its prognostic correlation by using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus Series (GSE81809) databases. Further, the CRISPR-Cas9 system was employed to establish SHMT2-knockout lung adenocarcinoma (LUAD) cell lines, assessing its impact on cell proliferation and apoptosis through various in vitro assays and in vivo nude mouse xenograft models. Mitochondrial homeostasis was evaluated by assessing the ROS levels, mitochondrial morphology, and membrane potential. Meanwhile, the SHMT2 inhibitor SHIN1 and the ROS scavenger N-Acetylcysteine (NAC) were employed to validate the underlying mechanism.

RESULTS: The results revealed that SHMT2 was significantly overexpressed in LUAD tissues and was associated with poor patient prognosis. SHMT2-knockout as well as SHIN1-treatment significantly inhibited the proliferation of LUAD cells and induced ROS-dependent mitochondrial apoptosis. Mechanistically, SHMT2 deficiency could increase the recruitment of BAX to mitochondria, reducing ΔΨm, and release of Cytochrome C (Cyto C) from mitochondria, thereby activating the caspase cascade and initiating intrinsic mitochondrial apoptosis. NAC treatment can reverse the apoptosis and mitochondrial dysfunction induced by SHMT2 knockout. In vivo experiments further confirmed that SHMT2 knockout significantly inhibited tumor growth, whereas ROS scavenging attenuated its antitumor effects.

CONCLUSIONS: Our findings suggest that SHMT2 is vital for regulating LUAD apoptosis by maintaining mitochondrial ROS homeostasis, and its deficiency triggers apoptosis through the ROS-BAX-Cyto C-Caspase signaling. Targeting SHMT2 could thus offer new clinical insights and be a promising strategy for LUAD treatment.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07975-9.},
}

@article {pmid42011586,
year = {2026},
author = {Chen, J and Zhang, H and Guo, YJ and Li, JR and Liu, BB and Ji, ES and Li, DL},
title = {[Danggui Buxue Decoction delays vascular endothelial cell senescence induced by intermittent hypoxia through regulating Nrf2].},
journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica},
volume = {51},
number = {5},
pages = {1390-1400},
doi = {10.19540/j.cnki.cjcmm.20251114.801},
pmid = {42011586},
issn = {1001-5302},
mesh = {Animals ; *NF-E2-Related Factor 2/metabolism/genetics ; *Drugs, Chinese Herbal/pharmacology/administration & dosage ; *Cellular Senescence/drug effects ; *Endothelial Cells/drug effects/metabolism/cytology ; Mice ; Mice, Inbred C57BL ; Male ; Oxidative Stress/drug effects ; Sirtuin 1/metabolism/genetics ; *Hypoxia/metabolism/drug therapy/physiopathology/genetics ; },
abstract = {This study aims to explore the antioxidant molecular mechanism of Danggui Buxue Decoction(DBD) in delaying the vascular endothelial cell senescence induced by intermittent hypoxia(IH). The C57BL/6N mouse model of chronic intermittent hypoxia(CIH) was established under 5%-21% O_2, 20 cycles·h~(-1), 8 h·d~(-1) and administrated with DBD(4.68 g·kg~(-1)·d~(-1)) by gavage. The IH model of mouse thoracic aortic endothelial cells was established(0.1% O_2 3 min-21% O_2 7 min, 6 cycles·h~(-1)). The cells were then treated with the antioxidant N-acetylcysteine(NAC), DBD-containing serum, or DBD-containing serum plus nuclear factor-erythroid 2-related factor 2(Nrf2) siRNA. The vascular function, pathological changes, and the aging condition of the aorta tissue in mice were detected. The senescence status of cells, the level of oxidative stress, mitochondrial membrane potential, and the apoptosis level were measured via commercial kits. The expression levels of silent information regulator 1(SIRT1), tumor protein p53, superoxide dismutase 2(SOD2), nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2), Kelch-like ECH-associated protein 1(Keap1), Nrf2, heme oxygenase-1(HO-1), B cell-lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific proteinase-3(Caspase-3) were determined by Western blot or Real-time fluorescence quantitative PCR. The results showed that DBD significantly improved the vascular function and attenuated the vascular endothelial damage and senescence in mice. Compared with the IH group, 5% DBD-containing serum or 1 mmol·L~(-1) NAC significantly increased the proliferation level of endothelial cells, promoted the expression of SIRT1, Nrf2, and HO-1 at protein and mRNA levels in endothelial cells, raised the expression level of SOD2, the mitochondrial membrane potential, and the mRNA level of Bcl-2, while significantly reducing the number of senescent cells, the expression of p53 and Keap1 at protein and mRNA levels, the content of reactive oxygen species in endothelial cells, the protein level of NOX2, and the mRNA levels of Bax and Caspase-3. The above-mentioned therapeutic effects were inhibited after intervention with Nrf2 siRNA. These results suggest that DBD alleviates the oxidative stress and inhibits the apoptosis of endothelial cells by activating the Nrf2 signaling pathway, thereby slowing down endothelial cell senescence under IH exposure.},
}

Animals
*NF-E2-Related Factor 2/metabolism/genetics
*Drugs, Chinese Herbal/pharmacology/administration & dosage
*Cellular Senescence/drug effects
*Endothelial Cells/drug effects/metabolism/cytology
Mice
Mice, Inbred C57BL
Male
Oxidative Stress/drug effects
Sirtuin 1/metabolism/genetics
*Hypoxia/metabolism/drug therapy/physiopathology/genetics

@article {pmid42012260,
year = {2026},
author = {Strojny, Z and Sikora, W and Hoffmann-Aulich, J and Kanikowska, D and Bręborowicz, A},
title = {Antisenescent and antiinflammatory effect of N-acetylcysteine in peritoneal mesothelial cells.},
journal = {Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis},
volume = {},
number = {},
pages = {8968608261443578},
doi = {10.1177/08968608261443578},
pmid = {42012260},
issn = {1718-4304},
abstract = {BackgroundPeritoneal dialysis induces an intraperitoneal inflammatory reaction, which causes damage to the peritoneum. Inflammation also accelerates cellular senescence. We studied in vitro effect of the dialysates from peritoneal dialysis patients on the senescence of the peritoneal mesothelial cells (MCs). The effect of N-acetylcysteine (NAC) on that process was studied.MethodsReplicative senescence was induced in MC cells exposed to culture medium, medium mixed with the dialysate ± NAC 0.025 mmol/L. After 10 passages, markers of the cellular senescence and secretory activity of the cells were measured. Additionally, the effect of NAC on the senescent cells was studied.ResultsExposure of MC to the dialysate accelerated, more than in medium alone, their senescence as reflected by elongation of the population doubling time, increased expression of p21, p53 genes and β-galactosidase activity. Secretion of IL6 and transforming growth factor β (TGFβ) was increased, and fibrinolytic activity, as reflected by the tissue plasminogen activator/plasminogen activator inhibitor-1 ratio, was reduced. NAC slowed down the process of senescence in MC treated with the dialysate. NAC suppressed the proinflammatory properties of the senescent MC.ConclusionThe proinflammatory properties of the peritoneal dialysate accelerate the senescence of MC. Decreased fibrinolytic activity of MC, increased secretion of IL6 and TGFβ may accelerate fibrosis of the peritoneum. Supplementation of NAC in patients treated with peritoneal dialysis may help preserve the peritoneum as the dialysis membrane.},
}

@article {pmid42013074,
year = {2026},
author = {Xu, H and Cao, M and Wang, Q and Ju, Y and Wang, X and Liu, Q and Zeng, T and Chen, X},
title = {Effects of N-acetyl-L-cysteine on sperm quality during chilled storage of Maguan hornless goat semen.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0347756},
doi = {10.1371/journal.pone.0347756},
pmid = {42013074},
issn = {1932-6203},
mesh = {Animals ; Male ; *Acetylcysteine/pharmacology ; *Semen Preservation/methods/veterinary ; *Spermatozoa/drug effects/metabolism ; Goats ; *Semen Analysis/veterinary ; Reactive Oxygen Species/metabolism ; *Semen/drug effects/metabolism ; Apoptosis/drug effects ; Antioxidants/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Oxidative Stress/drug effects ; Sperm Motility/drug effects ; },
abstract = {The Maguan hornless goat is a valuable indigenous goat breed in Yunnan Province, China. As a rare and endangered genetic resource, its population protection and breeding are challenged by numerous challenges, particularly during artificial insemination procedures. During chilled storage, sperm generate excessive levels of reactive oxygen species (ROS), which disrupt the integrity of the sperm plasma membrane, damage the celluar structures, and lead to a decline in semen quality. This study investigated the effects of different concentrations (0, 5, 7, 9 mM) of N-acetylcysteine (NAC) on the chilled storage of semen collected from Maguan hornless goats. Semen was collected from four healthy rams with normal reproductive performance. The different concentrations of NAC were added to the semen diluent, and the samples were diluted 10-fold prior to storage at 4 °C for up to 72 h. After defining storage intervals, sperm kinetics, antioxidant gene transcription, and oxidative stress-related enzymatic activity were analyzed. Results showed that sperm samples extended in diluent supplemented with 7 mM NAC and subjected to 72 h of chilled storage at 4 ℃ exhibited improved antioxidant levels. This approach also reduced sperm apoptosis, enhanced membrane integrity and mitochondrial membrane potential, and suppressed the expression of pro-apoptotic genes (BAX, Caspase 3) while upregulating that of antioxidant genes (GPX4, GPX1). The results suggest NAC supports semen chilled storage in endangered species by enhancing antioxidant capacity and inhibiting cell death-related pathways. This study provides insights into the application of reproductive biotechnology in small ruminants.},
}

Animals
Male
*Acetylcysteine/pharmacology
*Semen Preservation/methods/veterinary
*Spermatozoa/drug effects/metabolism
Goats
*Semen Analysis/veterinary
Reactive Oxygen Species/metabolism
*Semen/drug effects/metabolism
Apoptosis/drug effects
Antioxidants/metabolism
Membrane Potential, Mitochondrial/drug effects
Oxidative Stress/drug effects
Sperm Motility/drug effects

@article {pmid42013574,
year = {2026},
author = {Hartmann, RJ and Pradhan, S and Bylyku, D and Markieta, K and Scozzafava, J and Lucyk, S and Yarema, M},
title = {Cerebral Edema and Brain Death Following Intravenous N-Acetylcysteine Overdose: A Case Report.},
journal = {Canadian journal of physiology and pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1139/cjpp-2025-0341},
pmid = {42013574},
issn = {1205-7541},
abstract = {N-acetylcysteine (NAC) infusions are rarely associated with cerebral edema. We present a patient that received 1242.2 mg/kg intravenous NAC over 8.3 hours who developed seizures, cerebral edema, and died. A 17-24 year-old female (48.3 kg) presented after an acute acetaminophen ingestion. Their initial presumed five-hour acetaminophen concentration was 591.7 umol/L. Initial ALT and AST were 16 and 21 IU/L, respectively. Due to inconsistencies in the time of ingestion, IV NAC was initiated as a two-step protocol of 150 mg/kg over one hour followed by 15 mg/kg/hr for 20 hours. During treatment, the patient developed vomiting, flushing, and a maculopapular rash. It was discovered that NAC had been administered continuously at 150 mg/kg/hr for 8.3 hours and was stopped. The patient became confused and agitated, and subsequently developed seizures. They were treated with lorazepam, phenytoin, intubation, and propofol. Neuroimaging demonstrated cerebral edema with cerebellar tonsillar herniation. Despite neurocritical care, the patient died 86 hours post-ingestion. The patient's ALT and AST remained normal. Investigations including lumbar puncture and post-mortem toxicology analysis was unremarkable. Clinicians must be aware of the clinical features of supratherapeutic IV NAC dosing errors and potential adverse effects.},
}

@article {pmid42014372,
year = {2026},
author = {Fu, YY and Zhou, YF and Hu, HJ and Liu, YR and Zhang, ZQ and Han, GZ},
title = {Silica Promotes Silicosis via the ROS/NF-κB p65 Signaling-Activated Hypoxia-Lactate Axis in Rats.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70209},
pmid = {42014372},
issn = {1099-1263},
support = {202512041350//Medical and Health Science and Technology Development Project of Shandong Province/ ; },
abstract = {Hypoxia occurs during silicosis progression; however, the mechanisms by which silica induces hypoxia and its precise role in the pathogenesis remain poorly understood. In this study, 50 male rats were assigned to five groups: a control group, a model group, and three intervention groups. The rats in the model and intervention groups were intratracheally administered a silica suspension only once, whereas the control rats were intratracheally administered phosphate buffer solution (PBS). Then the rats in intervention groups received daily intravenous injections of N-acetylcysteine (NAC) (at doses of 20, 40, and 80 mg/kg, respectively) while the rats in control and model groups received PBS injections. After 60 days, the lung samples were harvested for histopathologic evaluation, and the hypoxia-related proteins (nuclear factor-κB p65 [NF-κB p65], hypoxia-inducible factor-1α [HIF-1α], and vascular endothelial growth factor A [VEGFA]), lactate-metabolism markers (glucose transporter type 1 [GLUT1] and lactate dehydrogenase A [LDHA]), and pulmonary-injury indicators (interleukin-1β [IL-1β] and transforming growth factor-β1 [TGF-β1]) were quantified using Western blot. The results showed that compared with the control group, the lung of the model group exhibited obvious damage and collagen deposition, accompanied by upregulation of the aforementioned cytokines. When NAC was employed to inhibit silica-induced ROS, all of the above phenomena were reversed in a dose-dependent manner. These findings indicated that silica induced pulmonary hypoxia via the ROS/NF-κB p65 pathway, which subsequently triggered inflammation and fibrosis through lactic acid fermentation, ultimately leading to silicosis.},
}

@article {pmid42001928,
year = {2026},
author = {Lin, Z and Hu, M and Li, R and Gong, X and Zhao, M and Zhang, H and Xuan, J and Qiao, W and Li, A},
title = {TDCIPP induces placental dysfunction and fetal growth restriction via oxidative stress-mediated PINK1/Parkin mitophagy.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {116103},
doi = {10.1016/j.fct.2026.116103},
pmid = {42001928},
issn = {1873-6351},
abstract = {Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate flame retardant increasingly linked to reproductive toxicity, yet its placental toxic mechanisms remain unclear. This study demonstrates that TDCIPP exposure disrupts placental homeostasis by inducing oxidative stress, which triggers excessive PINK1/Parkin-mediated mitophagy in both human trophoblasts (HTR-8/SVneo) and pregnant mice. Integrated network toxicology analysis predicted mitochondrial dysfunction and oxidative stress as central pathways, validated by upregulation of ATG5 and HMOX1, downregulation of SOD2, elevated ROS and mitochondrial superoxide, loss of mitochondrial membrane potential, and ultrastructural evidence of mitophagic vacuoles. TDCIPP activated the PINK1/Parkin pathway-evidenced by increased PINK1, Parkin, LC3-II/I, p62, reduced TOMM20, and enhanced Parkin-TOMM20 colocalization-while alternative mitophagy receptors FUNDC1 and BNIP3 remained unaffected. Mechanistically, oxidative stress acted upstream, as N-acetylcysteine (NAC) pretreatment suppressed ROS accumulation and PINK1/Parkin activation. Functionally, TDCIPP impaired trophoblast proliferation, induced apoptosis, and caused fetal growth restriction (FGR) in vivo. Notably, both genetic knockdown of Parkin in vitro and pharmacological inhibition of mitophagy with Mdivi-1 in vivo significantly alleviated trophoblast apoptosis and rescued placental and fetal weights. These findings establish that TDCIPP-induced placental injury is driven by an oxidative stress-PINK1/Parkin-mitophagy axis, revealing dysregulated mitophagy as a pivotal mechanism underlying TDCIPP-associated developmental toxicity and offering new insights into the reproductive risks of environmental flame retardant exposure.},
}

@article {pmid42004260,
year = {2026},
author = {Zhu, R and Li, DL and Zhang, BY and Zhang, FF and Zhou, K and Qin, GX and Wu, LF and Xie, FX},
title = {N-Acetylcysteine alleviates glycinin-induced intestinal damage in common carp: Multi-target regulation inhibiting apoptosis and restoring mucosal barrier integrity.},
journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)},
volume = {25},
number = {},
pages = {310-326},
pmid = {42004260},
issn = {2405-6383},
abstract = {Glycinin is a major anti-nutritional factor in soybeans and can induce growth inhibition and intestinal damage in aquatic animals. N-Acetylcysteine (NAC) possesses antioxidant and anti-inflammatory properties while promoting intestinal mucosal development. Therefore, this study aimed to elucidate the protective effects and underlying mechanisms of NAC against glycinin-induced intestinal damage in common carp (Cyprinus carpio). A total of 450 juvenile common carp (2.93 ± 0.03 g) were randomly assigned to five groups: a control group (CK), an 8.00% glycinin-damaged group (Gly), and three NAC-treated groups receiving 0.15%, 0.30% and 0.60% NAC supplementation (Gly-N1, Gly-N2, and Gly-N3). Each group contained three replicates for a 56-d feeding trial. Results showed that dietary 0.30%-0.60% NAC supplementation effectively alleviated the glycinin-induced impairments in growth performance and feed utilization, while concurrently restoring intestinal protease activity and muscle protein deposition (P < 0.05). The NAC mitigated the intestinal morphological damage induced by glycinin, including mucosal fold atrophy and microvilli shedding, and enhanced barrier integrity by upregulating the mRNA expression of tight junction proteins occludin, claudin-3, claudin-7 and zo-1, and reducing intestinal permeability (P < 0.05). Intestinal transcriptome analysis indicated NAC's ameliorative effects involving inflammation- and apoptosis-related pathways. Mechanistically, NAC exerted multi-target protection: it inhibited the MAPK/PI3K-AKT/NF-κB inflammatory network by downregulating the phosphorylation of p38, JNK, PI3K and AKT, and the expression of NF-κB p65, thereby inhibiting pro-inflammatory cytokines IL-1β and TNF-α release (P < 0.05). Concurrently, NAC activated the Nrf2 antioxidant pathway to counteract oxidative stress. Furthermore, NAC inhibited the mitochondrial apoptosis pathway by modulating Bcl-2/Bax expression and inhibiting Caspases activation, while restoring ATPase activity and membrane potential to improve intestinal mitochondrial function. In summary, dietary supplementation with 0.30%-0.60% NAC alleviated glycinin-induced intestinal damage through a multifaceted mechanism involving inhibition of inflammatory signaling, activation of antioxidant defense, and inhibition of mitochondrial apoptosis.},
}

@article {pmid39225404,
year = {2025},
author = {Chinnapaka, S and Bakthavachalam, V and Dasari, S and Kannan, J and Sapkota, S and Kumar, R and Munirathinam, G},
title = {Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells.},
journal = {BioFactors (Oxford, England)},
volume = {51},
number = {1},
pages = {e2117},
doi = {10.1002/biof.2117},
pmid = {39225404},
issn = {1872-8081},
mesh = {Humans ; Male ; *Apoptosis/drug effects ; Black or African American/genetics ; Cell Line, Tumor ; *Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; *Prostatic Neoplasms/pathology/drug therapy/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Receptors, Androgen/metabolism/genetics ; *Signal Transduction/drug effects ; Thioredoxin Reductase 2/metabolism/genetics ; *Vitamin K 3/pharmacology ; },
abstract = {Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.},
}

Humans
Male
*Apoptosis/drug effects
Black or African American/genetics
Cell Line, Tumor
*Cell Proliferation/drug effects
Gene Expression Regulation, Neoplastic/drug effects
*Prostatic Neoplasms/pathology/drug therapy/metabolism/genetics
Reactive Oxygen Species/metabolism
Receptors, Androgen/metabolism/genetics
*Signal Transduction/drug effects
Thioredoxin Reductase 2/metabolism/genetics
*Vitamin K 3/pharmacology

@article {pmid39232832,
year = {2024},
author = {Duan, H and Wang, F and Wang, K and Yang, S and Zhang, R and Xue, C and Zhang, L and Ma, X and Du, X and Kang, J and Zhang, Y and Zhao, X and Hu, J and Xiao, L},
title = {Quercetin ameliorates oxidative stress-induced apoptosis of granulosa cells in dairy cow follicular cysts by activating autophagy via the SIRT1/ROS/AMPK signaling pathway.},
journal = {Journal of animal science and biotechnology},
volume = {15},
number = {1},
pages = {119},
pmid = {39232832},
issn = {1674-9782},
abstract = {BACKGROUND: Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows.

RESULTS: In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries.

CONCLUSIONS: These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows.},
}

@article {pmid39239906,
year = {2024},
author = {Guo, J and Xu, Q and Zhong, Y and Su, Y},
title = {N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen Edwardsiella tarda.},
journal = {Virulence},
volume = {15},
number = {1},
pages = {2399983},
pmid = {39239906},
issn = {2150-5608},
mesh = {*Edwardsiella tarda/drug effects/genetics ; *Doxycycline/pharmacology ; *Anti-Bacterial Agents/pharmacology ; *Acetylcysteine/pharmacology ; *Drug Resistance, Bacterial ; Reactive Oxygen Species/metabolism ; Enterobacteriaceae Infections/microbiology/drug therapy ; Animals ; Glutathione/metabolism ; Proteomics ; Bacterial Proteins/genetics/metabolism ; Humans ; Microbial Sensitivity Tests ; },
abstract = {Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.},
}

*Edwardsiella tarda/drug effects/genetics
*Doxycycline/pharmacology
*Anti-Bacterial Agents/pharmacology
*Acetylcysteine/pharmacology
*Drug Resistance, Bacterial
Reactive Oxygen Species/metabolism
Enterobacteriaceae Infections/microbiology/drug therapy
Animals
Glutathione/metabolism
Proteomics
Bacterial Proteins/genetics/metabolism
Humans
Microbial Sensitivity Tests

@article {pmid39245103,
year = {2024},
author = {Mondal, S and Hazra, A and Paul, P and Saha, B and Roy, S and Bhowmick, P and Bhowmick, M},
title = {Formulation and evaluation of n-acetyl cysteine loaded bi-polymeric physically crosslinked hydrogel with antibacterial and antioxidant activity for diabetic wound dressing.},
journal = {International journal of biological macromolecules},
volume = {279},
number = {Pt 4},
pages = {135418},
doi = {10.1016/j.ijbiomac.2024.135418},
pmid = {39245103},
issn = {1879-0003},
mesh = {*Acetylcysteine/pharmacology/chemistry ; *Anti-Bacterial Agents/pharmacology/chemistry ; *Wound Healing/drug effects ; *Antioxidants/pharmacology/chemistry ; *Hydrogels/chemistry/pharmacology ; *Bandages ; Animals ; Humans ; Alginates/chemistry ; Microbial Sensitivity Tests ; Candida albicans/drug effects ; Drug Liberation ; Plant Gums/chemistry ; Escherichia coli/drug effects ; Rats ; Drug Compounding ; Mannans/chemistry/pharmacology ; },
abstract = {Diabetic wounds have become a serious global health concern, with a growing number of patients each year. Diabetic altered wound healing physiology, as well as resulting complications, make therapy difficult. Hence, diabetic wound healing necessitates a multidisciplinary strategy. This study focused on the formulation, statistical optimization, ex vivo, and in vitro evaluation of a diabetic wound healing by n-acetyl cysteine (NAC) loaded hydrogel. The objective of the study is to formulate n-acetyl loaded hydrogel with different ratio (1:1, 1:2, 1:3, 2:1) of sodium alginate and guar gum. The antibacterial and antifungal assessment against the viability of Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S.aureus) and Candida albicans (C. albicans) was conducted after determining the in vitro drug release profile. The results of the experiment demonstrated that the formulation F3 was an optimal formulation on triplicate measurement with a pH of 6.2 ± 0.168, and a density of 1.026 ± 0.21. In vitro cell line study exhibited F3 has potential role in cell adhesion and proliferation might be beneficial to tissue regeneration and wound healing. The results imply that F3 may be helpful for the quick healing of diabetic wounds by promoting angiogenesis and also by scavenging free oxygen radicals.},
}

*Acetylcysteine/pharmacology/chemistry
*Anti-Bacterial Agents/pharmacology/chemistry
*Wound Healing/drug effects
*Antioxidants/pharmacology/chemistry
*Hydrogels/chemistry/pharmacology
*Bandages
Animals
Humans
Alginates/chemistry
Microbial Sensitivity Tests
Candida albicans/drug effects
Drug Liberation
Plant Gums/chemistry
Escherichia coli/drug effects
Rats
Drug Compounding
Mannans/chemistry/pharmacology

@article {pmid39245438,
year = {2025},
author = {Lee, TL and Shen, WC and Chen, YC and Lai, TC and Lin, SR and Lin, SW and Yu, IS and Yeh, YH and Li, TK and Lee, IT and Lee, CW and Chen, YL},
title = {Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway.},
journal = {Autophagy},
volume = {21},
number = {2},
pages = {374-393},
pmid = {39245438},
issn = {1554-8635},
mesh = {Animals ; *MicroRNAs/metabolism/genetics ; *Myocardial Reperfusion Injury/metabolism/pathology/genetics ; *Exosomes/metabolism ; Microtubule-Associated Proteins/metabolism ; Myocytes, Cardiac/metabolism/drug effects/pathology ; *Membrane Proteins/metabolism ; Mice ; Mitophagy/drug effects ; Signal Transduction/drug effects ; *Particulate Matter/toxicity/adverse effects ; *Mitochondrial Proteins/metabolism ; *Apoptosis Regulatory Proteins/metabolism ; Apoptosis/drug effects ; Male ; Rats ; Mice, Inbred C57BL ; Proto-Oncogene Proteins/metabolism ; Mice, Transgenic ; Cell Line ; Autophagy ; },
abstract = {Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Mir221 and Mir222. The present study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of Mir221 and Mir222 in ADSC-Exos. Wild-type, mir221- and mir222-knockout (KO), and Mir221- and Mir222-overexpressing transgenic (TG) mice were intratracheally injected with PM (10 mg/kg). After 24 h, mice underwent left coronary artery ligation for 30 min, followed by 3 h of reperfusion (I/R). H9c2 cardiomyocytes were cultured under 1% O2 for 6 h, then reoxygenated for 12 h (hypoxia-reoxygenation [H/R]). PM aggravated I/R (or H/R) cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, which increased the expression of mitochondrial fission-related proteins (DNM1L/Drp1 and MFF) and mitophagy-related proteins (BNIP3 and MAP1LC3B/LC3B) in vivo and in vitro. Treatment with ADSC-Exos or Mir221- and Mir222-mimics significantly reduced PM+I/R-induced cardiac injury. Importantly, ADSC-Exos contain Mir221 and Mir222, which directly targets BNIP3, MAP1LC3B/LC3B, and BBC3/PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. The present data showed that ADSC-Exos treatment regulated mitophagy and apoptosis through the Mir221 and Mir222-BNIP3-MAP1LC3B-BBC3/PUMA pathway and significantly reduced the cardiac damage caused by PM+I/R. The present study revealed the novel therapeutic potential of ADSC-Exos in alleviating PM-induced exacerbation of myocardial I/R injury.Abbreviation: ADSC-Exos: adipose-derived stem cell exosomes; AL: autolysosome; ATP: adenosine triphosphate; BBC3/PUMA: BCL2 binding component 3; BNIP3: BCL2/adenovirus E1B interacting protein 3; CASP3: caspase 3; CASP9: caspase 9; CDKN1B/p27: cyclin dependent kinase inhibitor 1B; CVD: cardiovascular disease; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DHE: dihydroethidium; DNM1L/Drp1: dynamin 1-like; EF: ejection fraction; FS: fractional shortening; H/R: hypoxia-reoxygenation; I/R: ischemia-reperfusion; LDH: lactate dehydrogenase; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFF: mitochondrial fission factor; miRNA: microRNA; NAC: N-acetylcysteine; OCR: oxygen consumption rate; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PM: particulate matter; PRKAA1/AMPK: protein kinase AMP-activated catalytic subunit alpha 1; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TRP53/p53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.},
}

Animals
*MicroRNAs/metabolism/genetics
*Myocardial Reperfusion Injury/metabolism/pathology/genetics
*Exosomes/metabolism
Microtubule-Associated Proteins/metabolism
Myocytes, Cardiac/metabolism/drug effects/pathology
*Membrane Proteins/metabolism
Mice
Mitophagy/drug effects
Signal Transduction/drug effects
*Particulate Matter/toxicity/adverse effects
*Mitochondrial Proteins/metabolism
*Apoptosis Regulatory Proteins/metabolism
Apoptosis/drug effects
Male
Rats
Mice, Inbred C57BL
Proto-Oncogene Proteins/metabolism
Mice, Transgenic
Cell Line
Autophagy

@article {pmid39246710,
year = {2024},
author = {Abolfazli, S and Foroumand, S and Mohammadi, E and Ahangar, N and Kheirandish, A and Fathi, H and Mohammadi, H},
title = {Brain mitochondrial damage attenuation by quercetin and N-acetyl cysteine: peripheral and central antiemetic effects.},
journal = {Toxicology research},
volume = {13},
number = {5},
pages = {tfae139},
pmid = {39246710},
issn = {2045-452X},
abstract = {Nausea serves as a protective mechanism in organisms to prevent excessive consumption of toxic substances. Due to the adverse effects of chemical anti-nausea drugs, there is a growing interest in using herbal remedies and natural antioxidants. In this study, we evaluated the neuroprotective effects of quercetin (QU) and N-acetylcysteine (NAC) against oxidative damage induced by nausea. Emesis was induced in chickens using ipecac and copper sulfate (600 and 60 mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200 mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2 mg/kg) for one-time. Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC), glutathione level (GSH), and reactive oxygen species (ROS) as oxidative damage biomarkers were evaluated in the chicken's brain mitochondria. QU and NAC significantly reduced emesis induced by copper sulfate and ipecac compared to the control group (P < 0.001). Significant differences in oxidative damage were observed in the groups received of copper sulfate and ipecac compared with control group. Levels of LPO, ROS, and PC were significantly decreased after the administration of QU and NAC in emesis induced by copper sulfate and ipecac. While, mitochondrial function and GSH levels were increased after the administration of QU and NAC. Combination therapy with QU and NAC yielded the most effective results. This study suggests that QU and NAC possess antiemetic effects through both peripheral and central mechanisms and exhibit neuroprotective effects against oxidative brain damage induced by emesis by increasing plasma antioxidants or scavenging free radicals.},
}

@article {pmid39248027,
year = {2024},
author = {Thakkar, Y and Kobets, T and Api, AM and Duan, JD and Williams, GM},
title = {Assessment of genotoxic potential of fragrance materials in the chicken egg assays.},
journal = {Environmental and molecular mutagenesis},
volume = {65},
number = {8},
pages = {261-274},
doi = {10.1002/em.22627},
pmid = {39248027},
issn = {1098-2280},
mesh = {Animals ; *Chickens ; *Micronucleus Tests/methods ; *Mutagenicity Tests/methods ; *DNA Damage/drug effects ; *Perfume/toxicity ; Mutagens/toxicity ; Aldehydes/toxicity ; Ovum/drug effects ; Acrolein/toxicity/analogs & derivatives ; },
abstract = {The genotoxic and clastogenic/aneugeneic potentials of four α,β-unsaturated aldehydes, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal, 2-methyl-2-pentenal, and p-methoxy cinnamaldehyde, which are used as fragrance materials, were assessed using the Chicken Egg Genotoxicity Assay (CEGA) and the Hen's egg micronucleus (HET-MN) assay, respectively. Selection of materials was based on their chemical structures and the results of their previous assessment in the regulatory in vitro and/or in vivo genotoxicity test battery. Three tested materials, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal, and 2-methyl-2-pentenal, were negative in both, CEGA and HET-MN assays. These findings were congruent with the results of regulatory in vivo genotoxicity assays. In contrast, p-methoxy cinnamaldehyde, which was also negative in the in vivo genotoxicity assays, produced evidence of DNA damage, including DNA strand breaks and DNA adducts in CEGA. However, no increase in the micronucleus formation in blood was reported in the HET-MN study. Such variation in responses between the CEGA and HET-MN assay can be attributed to differences in the dosing protocols. Pretreatment with a glutathione precursor, N-acetyl cysteine, negated positive outcomes produced by p-methoxy cinnamaldehyde in CEGA, indicating that difference in response observed in the chicken egg and rodent models can be attributed to rapid glutathione depletion. Overall, our findings support the conclusion that CEGA and/or HET-MN can be considered as a potential alternative to animal testing as follow-up strategies for assessment of genotoxic potential of fragrance materials with evidence of genotoxicity in vitro.},
}

Animals
*Chickens
*Micronucleus Tests/methods
*Mutagenicity Tests/methods
*DNA Damage/drug effects
*Perfume/toxicity
Mutagens/toxicity
Aldehydes/toxicity
Ovum/drug effects
Acrolein/toxicity/analogs & derivatives

@article {pmid39251036,
year = {2024},
author = {Moyano, P and Flores, A and San Juan, J and García, J and Anadón, MJ and Plaza, JC and Naval, MV and Fernández, MC and Guerra-Menéndez, L and Del Pino, J},
title = {Imidacloprid unique and repeated treatment produces cholinergic transmission disruption and apoptotic cell death in SN56 cells.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {193},
number = {},
pages = {114988},
doi = {10.1016/j.fct.2024.114988},
pmid = {39251036},
issn = {1873-6351},
mesh = {Animals ; *Apoptosis/drug effects ; *Acetylcholinesterase/metabolism ; *Neonicotinoids/toxicity ; *tau Proteins/metabolism/genetics ; Mice ; NF-E2-Related Factor 2/metabolism/genetics ; Synaptic Transmission/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism/genetics ; Insecticides/toxicity ; Reactive Oxygen Species/metabolism ; HSP70 Heat-Shock Proteins/metabolism/genetics ; Cholinergic Neurons/drug effects/metabolism ; Amyloid beta-Protein Precursor/metabolism/genetics ; Oxidative Stress/drug effects ; Cell Line ; Proteasome Endopeptidase Complex/metabolism/drug effects ; Amyloid Precursor Protein Secretases/metabolism/genetics ; Aspartic Acid Endopeptidases/metabolism/genetics ; Nitro Compounds ; },
abstract = {Imidacloprid (IMI), the most widely used worldwide neonicotinoid biocide, produces cognitive disorders after repeated and single treatment. However, little was studied about the possible mechanisms that produce this effect. Cholinergic neurotransmission regulates cognitive function. Most cholinergic neuronal bodies are present in the basal forebrain (BF), regulating memory and learning process, and their dysfunction or loss produces cognition decline. BF SN56 cholinergic wild-type or acetylcholinesterase (AChE), β-amyloid-precursor-protein (βAPP), Tau, glycogen-synthase-kinase-3-beta (GSK3β), beta-site-amyloid-precursor-protein-cleaving enzyme 1 (BACE1), and/or nuclear-factor-erythroid-2-related-factor-2 (NRF2) silenced cells were treated for 1 and 14 days with IMI (1 μM-800 μM) with or without recombinant heat-shock-protein-70 (rHSP70), recombinant proteasome 20S (rP20S) and with or without N-acetyl-cysteine (NAC) to determine the possible mechanisms that mediate this effect. IMI treatment for 1 and 14 days altered cholinergic transmission through AChE inhibition, and triggered cell death partially through oxidative stress generation, AChE-S overexpression, HSP70 downregulation, P20S inhibition, and Aβ and Tau peptides accumulation. IMI produced oxidative stress through reactive oxygen species production and antioxidant NRF2 pathway downregulation, and induced Aβ and Tau accumulation through BACE1, GSK3β, HSP70, and P20S dysfunction. These results may assist in determining the mechanisms that produce cognitive dysfunction observed following IMI exposure and provide new therapeutic tools.},
}

Animals
*Apoptosis/drug effects
*Acetylcholinesterase/metabolism
*Neonicotinoids/toxicity
*tau Proteins/metabolism/genetics
Mice
NF-E2-Related Factor 2/metabolism/genetics
Synaptic Transmission/drug effects
Glycogen Synthase Kinase 3 beta/metabolism/genetics
Insecticides/toxicity
Reactive Oxygen Species/metabolism
HSP70 Heat-Shock Proteins/metabolism/genetics
Cholinergic Neurons/drug effects/metabolism
Amyloid beta-Protein Precursor/metabolism/genetics
Oxidative Stress/drug effects
Cell Line
Proteasome Endopeptidase Complex/metabolism/drug effects
Amyloid Precursor Protein Secretases/metabolism/genetics
Aspartic Acid Endopeptidases/metabolism/genetics
Nitro Compounds

@article {pmid39251120,
year = {2024},
author = {Wood, JPM and Chidlow, G and Wall, GM and Casson, RJ},
title = {N-acetylcysteine amide and di- N-acetylcysteine amide protect retinal cells in culture via an antioxidant action.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110074},
doi = {10.1016/j.exer.2024.110074},
pmid = {39251120},
issn = {1096-0007},
mesh = {Animals ; *Acetylcysteine/pharmacology/analogs & derivatives ; Rats ; *Oxidative Stress/drug effects ; Cells, Cultured ; *Retinal Ganglion Cells/drug effects/metabolism ; *Antioxidants/pharmacology ; *Reactive Oxygen Species/metabolism ; Glutathione/metabolism ; Cell Survival/drug effects ; Neuroglia/drug effects/metabolism ; Retina/drug effects/metabolism ; Dose-Response Relationship, Drug ; },
abstract = {Reactive oxygen species (ROS) play a significant role in toxicity to the retina in a variety of diseases. N-acetylcysteine (NAC), N-acetylcysteine amide (NACA) and the dimeric di-N-acetylcysteine amide (diNACA) were evaluated in terms of protecting retinal cells, in vitro, in a variety of stress models. Three types of rat retinal cell cultures were utilized in the study: macroglial-only cell cultures, neuron-only retinal ganglion cell (RGC) cultures, and mixed cultures containing retinal glia and neurons. Ability of test agents to attenuate oxidative stress in all cultures was ascertained. In addition, capability of agents to protect against a variety of alternate clinically-relevant stressors, including excitotoxins and mitochondrial electron transport chain inhibitors, was also evaluated. Capacity of test agents to elevate cellular levels of reduced glutathione under normal and compromised conditions was also determined. NAC, NACA and diNACA demonstrated concentration-dependent cytoprotection against oxidative stress in all cultures. These three compounds, however, had differing effects against a variety of alternate insults to retinal cells. The most protective agent was NACA, which was most potent against the most stressors (including oxidative stress, mitochondrial impairment by antimycin A and azide, and glutamate-induced excitotoxicity). Similar to NAC, NACA increased glutathione levels in non-injured cells, although diNACA did not, suggesting a different, unknown mechanism of antioxidant activity for the latter. In support of this, diNACA was the only agent to attenuate rotenone-induced toxicity in mitochondria. NAC, NACA and diNACA exhibited varying degrees of antioxidant activity, i.e., protected cultured rat retinal cells from a variety of stressors which were designed to mimic aspects of the pathology of different retinal diseases. A general rank order of activity was observed: NACA ≥ diNACA > NAC. These results warrant further exploration of NACA and diNACA as antioxidant therapeutics for the treatment of retinal diseases, particularly those involving oxidative stress. Furthermore, we have defined the battery of tests carried out as the "Wood, Chidlow, Wall and Casson (WCWC) Retinal Antioxidant Indices"; we believe that these are of great value for screening molecules for potential to reduce retinal oxidative stress in a range of retinal diseases.},
}

Animals
*Acetylcysteine/pharmacology/analogs & derivatives
Rats
*Oxidative Stress/drug effects
Cells, Cultured
*Retinal Ganglion Cells/drug effects/metabolism
*Antioxidants/pharmacology
*Reactive Oxygen Species/metabolism
Glutathione/metabolism
Cell Survival/drug effects
Neuroglia/drug effects/metabolism
Retina/drug effects/metabolism
Dose-Response Relationship, Drug

@article {pmid39257692,
year = {2024},
author = {De Felice, M and Szkudlarek, HJ and Uzuneser, TC and Rodríguez-Ruiz, M and Sarikahya, MH and Pusparajah, M and Galindo Lazo, JP and Whitehead, SN and Yeung, KK and Rushlow, WJ and Laviolette, SR},
title = {The Impacts of Adolescent Cannabinoid Exposure on Striatal Anxiety- and Depressive-Like Pathophysiology Are Prevented by the Antioxidant N-Acetylcysteine.},
journal = {Biological psychiatry global open science},
volume = {4},
number = {6},
pages = {100361},
pmid = {39257692},
issn = {2667-1743},
abstract = {BACKGROUND: Exposure to Δ[9]-tetrahydrocannabinol (THC) is an established risk factor for later-life neuropsychiatric vulnerability, including mood- and anxiety-related symptoms. The psychotropic effects of THC on affect and anxiogenic behavioral phenomena are known to target the striatal network, particularly the nucleus accumbens, a neural region linked to mood and anxiety disorder pathophysiology. THC may increase neuroinflammatory responses via the redox system and dysregulate inhibitory and excitatory neural balance in various brain circuits, including the striatum. Thus, interventions that can induce antioxidant effects may counteract the neurodevelopmental impacts of THC exposure.

METHODS: In the current study, we used an established preclinical adolescent rat model to examine the impacts of adolescent THC exposure on various behavioral, molecular, and neuronal biomarkers associated with increased mood and anxiety disorder vulnerability. Moreover, we investigated the protective properties of the antioxidant N-acetylcysteine against THC-related pathology.

RESULTS: We demonstrated that adolescent THC exposure induced long-lasting anxiety- and depressive-like phenotypes concomitant with differential neuronal and molecular abnormalities in the two subregions of the nucleus accumbens, the shell and the core. In addition, we report for the first time that N-acetylcysteine can prevent THC-induced accumbal pathophysiology and associated behavioral abnormalities.

CONCLUSIONS: The preventive effects of this antioxidant intervention highlight the critical role of redox mechanisms underlying cannabinoid-induced neurodevelopmental pathology and identify a potential intervention strategy for the prevention and/or reversal of these pathophysiological sequelae.},
}

@article {pmid39258904,
year = {2024},
author = {Chae, IG and Jung, J and Kim, DH and Choi, JS and Chun, KS},
title = {EP4 receptor agonist CAY10598 upregulates ROS-dependent Hsp90 cleavage in colorectal cancer cells.},
journal = {Free radical research},
volume = {58},
number = {10},
pages = {596-605},
doi = {10.1080/10715762.2024.2396909},
pmid = {39258904},
issn = {1029-2470},
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Colorectal Neoplasms/metabolism/drug therapy/pathology ; *Receptors, Prostaglandin E, EP4 Subtype/agonists/metabolism ; *HSP90 Heat-Shock Proteins/metabolism ; Mice ; Animals ; Up-Regulation/drug effects ; HCT116 Cells ; Mice, Nude ; },
abstract = {Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and β isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.},
}

Humans
*Reactive Oxygen Species/metabolism
*Colorectal Neoplasms/metabolism/drug therapy/pathology
*Receptors, Prostaglandin E, EP4 Subtype/agonists/metabolism
*HSP90 Heat-Shock Proteins/metabolism
Mice
Animals
Up-Regulation/drug effects
HCT116 Cells
Mice, Nude

@article {pmid39260547,
year = {2024},
author = {Das, S and Mukherjee, U and Biswas, S and Banerjee, S and Karmakar, S and Maitra, S},
title = {Unravelling bisphenol A-induced hepatotoxicity: Insights into oxidative stress, inflammation, and energy dysregulation.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {362},
number = {},
pages = {124922},
doi = {10.1016/j.envpol.2024.124922},
pmid = {39260547},
issn = {1873-6424},
mesh = {Animals ; *Phenols/toxicity ; *Benzhydryl Compounds/toxicity ; Mice ; Male ; *Oxidative Stress/drug effects ; *Inflammation/chemically induced/metabolism ; Endocrine Disruptors/toxicity ; Reactive Oxygen Species/metabolism ; Liver/metabolism/drug effects ; NF-kappa B/metabolism ; Inflammasomes/metabolism ; Chemical and Drug Induced Liver Injury/metabolism ; Energy Metabolism/drug effects ; Bisphenol A Compounds ; },
abstract = {Bisphenol A (BPA), a prevalent plastic monomer and endocrine disruptor, negatively impacts metabolic functions. This study examines the chronic effects of eco-relevant BPA concentrations on hepatotoxicity, focusing on redox balance, inflammatory response, cellular energy sensors, and metabolic homeostasis in male Swiss albino mice. Chronic BPA exposure resulted in reactive oxygen species (ROS) accumulation, altered hepatic antioxidant defense, lipid peroxidation, and NOX4 expression, leading to reduced cell viability. Additionally, BPA exposure significantly upregulated hepatic pro-inflammatory cytokine genes (Tnf-α, Il-1β, Il-6), NOS2, and arginase II, correlating with increased TLR4 expression, NF-κB phosphorylation, and a dose-dependent decrease in IκBα levels. BPA-induced NF-κB nuclear localization and inflammasome activation (NLRP3, cleaved caspase-1, IL-1β) established an inflammatory milieu. Perturbations in hepatic AMPKα phosphorylation, SIRT1, and PGC-1α, along with elevated p38 MAPK phosphorylation and ERα expression, indicated BPA-induced energy dysregulation. Furthermore, increased PLA2G4A, COX1, COX2, and PTGES2 expression in BPA-treated liver correlated with hyperlipidemia, hepatic FASN expression, steatosis, and visceral adiposity, likely due to disrupted energy sensors, oxidative stress, and inflammasome activation. Elevated liver enzymes (ALP, AST, ALT) and apoptotic markers indicated liver damage. Notably, N-acetylcysteine (NAC) priming reversed BPA-induced hepatocellular ROS accumulation, NF-κB-inflammasome activation, and intracellular lipid accumulation, while upregulating cellular energy sensors and attenuating ERα expression, suggesting NAC's protective effects against BPA-induced hepatotoxicity. Pharmacological inhibition of the NF-κB/NLRP3 cascade in BAY11-7082 pretreated, or NLRP3 immunodepleted hepatocytes reversed BPA's negative impact on SIRT1/p-AMPKα/PGC-1α and intracellular lipid accumulation, providing mechanistic insights into BPA-induced metabolic disruption.},
}

Animals
*Phenols/toxicity
*Benzhydryl Compounds/toxicity
Mice
Male
*Oxidative Stress/drug effects
*Inflammation/chemically induced/metabolism
Endocrine Disruptors/toxicity
Reactive Oxygen Species/metabolism
Liver/metabolism/drug effects
NF-kappa B/metabolism
Inflammasomes/metabolism
Chemical and Drug Induced Liver Injury/metabolism
Energy Metabolism/drug effects
Bisphenol A Compounds

@article {pmid39262205,
year = {2025},
author = {González-Guzmán, D and Andrade-Castellanos, CA and Ponce-Gallegos, MA and Mesina-Estarrón, I and Mora-Almanza, JG and Ruelas-Moreno, HE and Rodríguez-González, D and Eguia-Ortega, O and Colunga-Lozano, LE},
title = {N-acetyl-cysteine in Intensive Care Unit Patients with Acute Respiratory Distress Syndrome due to COVID-19: A Retrospective Cohort Study.},
journal = {Journal of intensive care medicine},
volume = {40},
number = {3},
pages = {284-293},
doi = {10.1177/08850666241281281},
pmid = {39262205},
issn = {1525-1489},
mesh = {Humans ; *Acetylcysteine/therapeutic use/administration & dosage ; *Respiratory Distress Syndrome/mortality/drug therapy/etiology/virology/therapy ; Male ; Female ; Middle Aged ; *COVID-19/complications/mortality ; Retrospective Studies ; Intensive Care Units ; Aged ; Respiration, Artificial ; Critical Illness ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Administration, Oral ; },
abstract = {COVID-19-related acute respiratory distress syndrome (ARDS) is linked to mortality, primarily due to a cytokine storm, oxidative stress imbalance, and pro-thrombotic state.PurposeWe assessed the potential association between N-acetyl-cysteine (NAC) and clinical outcomes in critically ill subjects with COVID-19-related ARDS.Material and MethodsWe included subjects with confirmed COVID-19 who were admitted to our ICU between March 1, 2020, and January 31, 2021, due to ARDS and necessitating invasive mechanical ventilation (IMV). Subjects who received standard of care (SOC) were compared with subjects who additionally received NAC 600 mg bid orally.ResultsA total of 243 subjects were included in this study. The results indicate significantly improved survival rates in the NAC plus SOC group, both in the unadjusted analysis and after adjusting for confounding factors such as ARDS severity (HR 0.48, 95% CI 0.32-0.70).ConclusionsWe found that oral administration of NAC was associated with reduced mortality in critically ill patients with COVID-19 related ARDS.},
}

Humans
*Acetylcysteine/therapeutic use/administration & dosage
*Respiratory Distress Syndrome/mortality/drug therapy/etiology/virology/therapy
Male
Female
Middle Aged
*COVID-19/complications/mortality
Retrospective Studies
Intensive Care Units
Aged
Respiration, Artificial
Critical Illness
SARS-CoV-2
*COVID-19 Drug Treatment
Administration, Oral

@article {pmid39263473,
year = {2024},
author = {Li, YL and Wang, G and Wang, BW and Li, YH and Ma, YX and Huang, Y and Yan, WT and Xie, P},
title = {The potential treatment of N-acetylcysteine as an antioxidant in the radiation-induced heart disease.},
journal = {Cardiovascular diagnosis and therapy},
volume = {14},
number = {4},
pages = {509-524},
pmid = {39263473},
issn = {2223-3652},
abstract = {BACKGROUND: Radiation-induced heart disease (RIHD) is a serious complication of thoracic tumor radiotherapy that substantially affects the quality of life of cancer patients. Oxidative stress plays a pivotal role in the occurrence and progression of RIHD, which prompted our investigation of an innovative approach for treating RIHD using antioxidant therapy.

METHODS: We used 8-week-old male Sprague-Dawley (SD) rats as experimental animals and H9C2 cells as experimental cells. N-acetylcysteine (NAC) was used as an antioxidant to treat H9C2 cells after X-ray irradiation in this study. In the present study, the extent of cardiomyocyte damage caused by X-ray exposure was determined, alterations in oxidation/antioxidation levels were assessed, and changes in the expression of genes related to mitochondria were examined. The degree of myocardial tissue and cell injury was also determined. Dihydroethidium (DHE) staining, reactive oxygen species (ROS) assays, and glutathione (GSH) and manganese superoxide dismutase (Mn-SOD) assays were used to assess cell oxidation/antioxidation. Flow cytometry was used to determine the mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening. High-throughput transcriptome sequencing and bioinformatics analysis were used to elucidate the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure. Polymerase chain reaction (PCR) was used to verify the expression of differentially expressed genes.

RESULTS: X-ray irradiation damaged myocardial tissue and cells, resulting in an imbalance of oxidative and antioxidant substances and mitochondrial damage. NAC treatment increased cell counting kit-8 (CCK-8) levels (P=0.02) and decreased lactate dehydrogenase (LDH) release (P=0.02) in cardiomyocytes. It also reduced the level of ROS (P=0.002) and increased the levels of GSH (P=0.04) and Mn-SOD (P=0.01). The mitochondrial membrane potential was restored (P<0.001), and mPTP opening was inhibited (P<0.001). Transcriptome sequencing and subsequent validation analyses revealed a decrease in the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure, but antioxidant therapy did not reverse the related DNA damage.

CONCLUSIONS: Antioxidants mitigated radiation-induced myocardial damage to a certain degree, but these agents did not reverse the associated DNA damage. These findings provide a new direction for future investigations by our research group, including exploring the treatment of RIHD-related DNA damage.},
}

@article {pmid39265812,
year = {2024},
author = {Pazarci, Ö and Hümeyra Taşkin Kafa, A and Taş, A and Keklikcioğlu Çakmak, N and Hasbek, M and Kilinç, S and Tunçbilek, Z},
title = {Assessment of the antimicrobial and antibiofilm activity of the combination of N-acetyl cysteine and carvacrol against Staphylococcus aureus, the most common orthopedic infectious agent.},
journal = {Microbial pathogenesis},
volume = {196},
number = {},
pages = {106934},
doi = {10.1016/j.micpath.2024.106934},
pmid = {39265812},
issn = {1096-1208},
mesh = {*Biofilms/drug effects ; *Cymenes/pharmacology ; *Acetylcysteine/pharmacology ; *Microbial Sensitivity Tests ; *Staphylococcus aureus/drug effects ; *Drug Synergism ; *Anti-Bacterial Agents/pharmacology ; Staphylococcal Infections/drug therapy/microbiology ; Monoterpenes/pharmacology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Cell Line ; },
abstract = {BACKGROUND: The increasing prevalence of antibiotic-resistant bacterial infections has led to the search for new approaches.

OBJECTIVE: This study aimed to evaluate the effects of carvacrol and N-acetyl cysteine, both individually and in combination, on the planktonic cells and biofilm formations of Staphylococcus aureus, including methicillin-resistant and methicillin-sensitive strains. Additionally, the study sought to perform cytotoxicity tests and chemical characterization to further understand the properties and potential applications of these substances.

METHODS: A total of 19 S. aureus strains were included in the study. Minimum inhibitory concentration and minimum bactericidal concentration were determined by assays. Synergy analysis tests were carried out. Cytotoxicity tests were conducted on the fibroblast cell line. Characterization test was performed.

RESULTS: While Minimum inhibitory concentration and minimum bactericidal concentration values for carvacrol varied between 250 and 500 μg/ml, these values were in the range of 32-64 mg/ml for N-acetyl cysteine. Biofilm formation activities were identified. A total of eight strains, including six clinical and two standard strains with the highest biofilm-forming ability, were selected for combination studies. The combination of Carvacrol and N-acetyl cysteine exhibited synergistic and partially synergistic effects on the tested planktonic and biofilm strains, and these effects were dose-dependent. Carvacrol was found to be the most active drug at the end of 24, 48, and 72 h. Regarding the synergistic effect of N-acetyl cysteine + carvacrol, it was revealed to exhibit higher activity than N-acetyl cysteine and lower activity than carvacrol.

CONCLUSION: The combination of carvacrol and N-acetyl cysteine demonstrated synergistic and partially synergistic effects against both planktonic and biofilm forms of Staphylococcus aureus. These results suggest potential for novel approaches in managing orthopedic infections, warranting further research to explore their therapeutic applications.},
}

*Biofilms/drug effects
*Cymenes/pharmacology
*Acetylcysteine/pharmacology
*Microbial Sensitivity Tests
*Staphylococcus aureus/drug effects
*Drug Synergism
*Anti-Bacterial Agents/pharmacology
Staphylococcal Infections/drug therapy/microbiology
Monoterpenes/pharmacology
Humans
Methicillin-Resistant Staphylococcus aureus/drug effects
Cell Line

@article {pmid39265983,
year = {2025},
author = {Sun, J and Ding, J and Yue, H and Xu, B and Sodhi, A and Xue, K and Ren, H and Qian, J},
title = {Hypoxia-induced BNIP3 facilitates the progression and metastasis of uveal melanoma by driving metabolic reprogramming.},
journal = {Autophagy},
volume = {21},
number = {1},
pages = {191-209},
pmid = {39265983},
issn = {1554-8635},
mesh = {*Melanoma/pathology/metabolism ; *Membrane Proteins/metabolism ; Humans ; *Uveal Neoplasms/pathology/metabolism ; *Mitophagy/physiology ; Animals ; *Disease Progression ; *Proto-Oncogene Proteins/metabolism ; Cell Line, Tumor ; *Neoplasm Metastasis ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mitochondria/metabolism ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism ; Mice ; Glycolysis ; Cell Hypoxia ; Mice, Nude ; Metabolic Reprogramming ; Uveal Melanoma ; },
abstract = {Uveal melanoma (UM) is an aggressive intraocular malignancy derived from melanocytes in the uvea tract of the eye. Up to 50% of patients with UM develop distant metastases which is usually fatal within one year; preventing metastases is therefore essential. Metabolic reprogramming plays a critical role in UM progression and metastasis. However, the metabolic phenotype of UM cells in the hypoxic tumor is not well understood. Here, we report that hypoxia-induced BNIP3 reprograms tumor cell metabolism, promoting their survival and metastasis. In response to hypoxia, BNIP3-mediated mitophagy alleviates mitochondrial dysfunction and enhances mitochondrial oxidative phosphorylation (OXPHOS) while simultaneously reducing mitochondrial reactive oxygen species (mtROS) production. This, in turn, impairs HIF1A/HIF-1α protein stability and inhibits glycolysis. Inhibition of mitophagy significantly suppresses BNIP3-induced UM progression and metastasis in vitro and in vivo. Collectively, these observations demonstrate a novel mechanism whereby BNIP3 promotes UM metabolic reprogramming and malignant progression by mediating hypoxia-induced mitophagy and suggest that BNIP3 could be an important therapeutic target to prevent metastasis in patients with UM.Abbreviations: AOD: average optical density; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine; CoCl2: cobalt chloride; GEPIA: Gene Expression Profiling Interactive Analysis; HIF1A: hypoxia inducible factor 1, alpha subunit; IHC: immunohistochemistry; mtROS: mitochondrial reactive oxygen species; NAC: N-acetylcysteine; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; ROS: reactive oxygen species; TCGA: The Cancer Genome Atlas; UM: uveal melanoma.},
}

*Melanoma/pathology/metabolism
*Membrane Proteins/metabolism
Humans
*Uveal Neoplasms/pathology/metabolism
*Mitophagy/physiology
Animals
*Disease Progression
*Proto-Oncogene Proteins/metabolism
Cell Line, Tumor
*Neoplasm Metastasis
*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
Mitochondria/metabolism
Oxidative Phosphorylation
Reactive Oxygen Species/metabolism
Mice
Glycolysis
Cell Hypoxia
Mice, Nude
Metabolic Reprogramming
Uveal Melanoma

@article {pmid39268103,
year = {2024},
author = {Zheng, J and Zhao, L and Liu, Y and Chen, M and Guo, X and Wang, J},
title = {N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.},
journal = {Journal of thoracic disease},
volume = {16},
number = {8},
pages = {5323-5336},
pmid = {39268103},
issn = {2072-1439},
abstract = {BACKGROUND: Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC.

METHODS: A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining.

RESULTS: We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC.

CONCLUSIONS: NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.},
}

@article {pmid39272966,
year = {2024},
author = {Gupta, KB and Taylor, TL and Panda, SS and Thangaraju, M and Lokeshwar, BL},
title = {Curcumin-Dichloroacetate Hybrid Molecule as an Antitumor Oral Drug against Multidrug-Resistant Advanced Bladder Cancers.},
journal = {Cancers},
volume = {16},
number = {17},
pages = {},
pmid = {39272966},
issn = {2072-6694},
support = {HT9425-23-1-0761//US Department of Defense Army Research program/ ; },
abstract = {Tumor cells produce excessive reactive oxygen species (ROS) but cannot detoxify ROS if they are due to an external agent. An agent that produces toxic levels of ROS, specifically in tumor cells, could be an effective anticancer drug. CMC-2 is a molecular hybrid of the bioactive polyphenol curcumin conjugated to dichloroacetate (DCA) via a glycine bridge. The CMC-2 was tested for its cytotoxic antitumor activities and killed both naïve and multidrug-resistant (MDR) bladder cancer (BCa) cells with equal potency (<1.0 µM); CMC-2 was about 10-15 folds more potent than curcumin or DCA. Growth of human BCa xenograft in mice was reduced by >50% by oral gavage of 50 mg/kg of CMC-2 without recognizable systemic toxicity. Doses that used curcumin or DCA showed minimum antitumor effects. In vitro, the toxicity of CMC-2 in both naïve and MDR cells depended on increased intracellular ROS in tumor cells but not in normal cells at comparable doses. Increased ROS caused the permeabilization of mitochondria and induced apoptosis. Further, adding N-Acetyl cysteine (NAC), a hydroxyl radical scavenger, abolished excessive ROS production and CMC-2's cytotoxicity. The lack of systemic toxicity, equal potency against chemotherapy -naïve and resistant tumors, and oral bioavailability establish the potential of CMC-2 as a potent drug against bladder cancers.},
}

@article {pmid39275957,
year = {2024},
author = {},
title = {RETRACTION "Protective effects of N-acetyl cysteine on lipid peroxide metabolism on isoproterenol-induced myocardial infarcted rats,".},
journal = {Journal of biochemical and molecular toxicology},
volume = {38},
number = {10},
pages = {e23852},
doi = {10.1002/jbt.23852},
pmid = {39275957},
issn = {1099-0461},
abstract = {M. F. Nagoor Meeran and P. S. Mainzen Prince, Journal of Biochemical and Molecular Toxicology 25, no. 3 (2011): 151-157, https://doi.org/10.1002/jbt.20371. The above article, published online on 23 November 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals, LLC. The retraction has been agreed due to duplication of several Western blot bands observed in Figure 2. The authors did not provide an explanation or their raw data. The editors consider the results and conclusion reported in this article unreliable.},
}

@article {pmid39276051,
year = {2024},
author = {Cong, X and Chen, T and Li, S and Wang, Y and Zhou, L and Li, X and Zhang, P and Sun, X and Zhao, S},
title = {[Dihydroartemisinin enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis by promoting ROS production].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {44},
number = {8},
pages = {1553-1560},
pmid = {39276051},
issn = {1673-4254},
mesh = {Humans ; *Cisplatin/pharmacology ; *Artemisinins/pharmacology ; *Apoptosis/drug effects ; *Nasopharyngeal Carcinoma/metabolism/pathology/drug therapy ; *Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; *Nasopharyngeal Neoplasms/metabolism/pathology/drug therapy ; *Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/drug effects ; Caspase 3/metabolism ; Caspase 9/metabolism ; Antineoplastic Agents/pharmacology ; },
abstract = {OBJECTIVE: To investigate the effect of dihydroartemisinin (DHA) for enhancing the inhibitory effect of cisplatin (DDP) on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.

METHODS: CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA (0, 5, 10, 20, 40, 80, and 160 μmol/L) and DDP (0, 4, 8, 16, 32, 64, 128 μmol/L) for 24 or 48 h, and the combination index of DHA and DDP was calculated using Compusyn software. HNE1/DDP cells treated with DHA, DDP, or their combination for 24 h were examined for cell viability, proliferation and colony formation ability using CCK-8, EdU and colony-forming assays. Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species (ROS). The expression levels of apoptosis-related proteins cleaved PARP, cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting. The effects of N-acetyl-cysteine (a ROS inhibitor) on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.

RESULTS: Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells. The combination index of DHA (5 μmol/L) combined with DDP (8, 16, 32, 64, 128 μmol/L) were all below 1. Compared with DHA or DDP alone, their combined treatment more potently decreased the cell viability, colony-forming ability and the number of EdU-positive cells, and significantly increased the apoptotic rate, intracellular ROS level, and the expression levels of cleaved PARP, cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells. N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells (P<0.01).

CONCLUSION: DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.},
}

Humans
*Cisplatin/pharmacology
*Artemisinins/pharmacology
*Apoptosis/drug effects
*Nasopharyngeal Carcinoma/metabolism/pathology/drug therapy
*Reactive Oxygen Species/metabolism
Cell Line, Tumor
*Nasopharyngeal Neoplasms/metabolism/pathology/drug therapy
*Cell Proliferation/drug effects
Cell Survival/drug effects
Drug Resistance, Neoplasm/drug effects
Caspase 3/metabolism
Caspase 9/metabolism
Antineoplastic Agents/pharmacology

@article {pmid39278392,
year = {2024},
author = {Wang, Z and Guo, L and Zhu, C and Li, J and Guo, J and Zhu, X and Li, J and Cui, L and Dong, J and Liu, K and Meng, X and Zhu, G and Wang, H},
title = {NLRP3 targets HMGB1 to exacerbate the pyroptosis of canine corneal epithelial cells infected with Staphylococcus pseudintermedius.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110096},
doi = {10.1016/j.exer.2024.110096},
pmid = {39278392},
issn = {1096-0007},
mesh = {Animals ; *Pyroptosis ; *HMGB1 Protein/metabolism/genetics ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Dogs ; *Epithelium, Corneal/metabolism/microbiology/drug effects ; *Reactive Oxygen Species/metabolism ; *Staphylococcus ; Staphylococcal Infections/microbiology/metabolism ; Eye Infections, Bacterial/microbiology/metabolism ; Cells, Cultured ; Blotting, Western ; Gene Expression Regulation ; RNA, Messenger/genetics/metabolism ; },
abstract = {PURPOSE: This study focused on the mechanisms of pyroptosis and oxidative damage exacerbation by NOD-like receptor thermal protein domain associated protein 3 (NLRP3) during the infection of canine corneal epithelial cells (CCECs) with Staphylococcus pseudintermedius.

METHODS: The CCECs treated with dimethyl fumarate (DMF), recombinant high mobility group protein 1 (HMGB1), or N-acetylcysteine (NAC). The gasdermin (GSDM) family and HMGB1 mRNA expression levels were detected using quantitative reverse transcription polymerase chain reaction. Lactate dehydrogenase activity, bacterial counts, the pyroptosis rate, reactive oxygen species (ROS) content, and antioxidant enzyme activity were used to reflect pyroptosis and oxidation level.

RESULTS: Regulation of NLRP3 significantly affected the pyroptosis rate and GSDMD-N expression levels during S. pseudintermedius infection. Inhibition of GSDMD-N protein activation by DMF reversed the exacerbation of pyroptosis induced by NLRP3 overexpression and reduced the levels of cleaved interleukin-1β (IL-1β), cleaved cysteinyl aspartate-specific protease-1, and NLRP3. In addition, NLRP3 was found to target the HMGB1 promoter and regulate its protein expression, to increase ROS accumulation and GSDMD-N expression levels, and activate the NLRP3-HMGB1-ROS-GSDMD signaling axis to aggravate pyroptosis during infection.

CONCLUSIONS: NLRP3 aggravates pyroptosis and oxidative damage associated with the activation of NLRP3-GSDMD and NLRP3-HMGB1-ROS-GSDMD signaling pathways during the infection of CCECs with S. pseudintermedius.},
}

Animals
*Pyroptosis
*HMGB1 Protein/metabolism/genetics
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
Dogs
*Epithelium, Corneal/metabolism/microbiology/drug effects
*Reactive Oxygen Species/metabolism
*Staphylococcus
Staphylococcal Infections/microbiology/metabolism
Eye Infections, Bacterial/microbiology/metabolism
Cells, Cultured
Blotting, Western
Gene Expression Regulation
RNA, Messenger/genetics/metabolism

@article {pmid39281865,
year = {2024},
author = {Bishop, A and Romero, JC and Tonapi, S and Parihar, M and Loranc, E and Miller, H and Lawrence, L and Bassani, N and Robledo, D and Cao, L and Nie, J and Kanda, K and Stoja, A and Garcia, N and Gorthi, A and Stoveken, B and Lane, A and Fan, T and Cassel, T and Zha, S and Musi, N},
title = {ATM phosphorylation of CD98HC increases antiporter membrane localization and prevents chronic toxic glutamate accumulation in Ataxia telangiectasia.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39281865},
issn = {2693-5015},
support = {T32 AG021890/AG/NIA NIH HHS/United States ; R01 CA241554/CA/NCI NIH HHS/United States ; F31 AG072902/AG/NIA NIH HHS/United States ; TL1 TR002647/TR/NCATS NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; K22 ES012264/ES/NIEHS NIH HHS/United States ; P30 CA177558/CA/NCI NIH HHS/United States ; T32 CA148724/CA/NCI NIH HHS/United States ; },
abstract = {Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by neurological defects, immunodeficiency, cancer predisposition, radiosensitivity, decreased blood vessel integrity, and diabetes. ATM, the protein mutated in A-T, responds to DNA damage and oxidative stress, but its functional relationship to the progressive clinical manifestation of A-T is not understood. CD98HC chaperones cystine/glutamate (xc [-]) and cationic/neutral amino acid (y[+]L) antiporters to the cell membrane, and CD98HC phosphorylation by ATM accelerates membrane localization to acutely increase amino acid transport. Loss of ATM impacts tissues reliant on SLC family antiporters relevant to A-T phenotypes, such as endothelial cells (telangiectasia) and pancreatic α-cells (fatty liver and diabetes) with toxic glutamate accumulation. Bypassing the antiporters restores intracellular metabolic balance both in ATM-deficient cells and mouse models. These findings provide new insight into the long-known benefits of N-acetyl cysteine to A-T cells beyond oxidative stress through removing excess glutamate by production of glutathione.},
}

@article {pmid39295440,
year = {2024},
author = {Brand, F and Bale, E and Tsiachristas, A and Hawton, K},
title = {Self-poisoning with paracetamol in England: short report of characteristics of individuals and their overdoses according to source of tablets.},
journal = {BJPsych open},
volume = {10},
number = {5},
pages = {e155},
pmid = {39295440},
issn = {2056-4724},
support = {//Department of Health and Social Care/ ; //National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley/ ; },
abstract = {Self-poisoning with paracetamol is the most frequently used overdose method in the UK. Psychosocial assessments were conducted by mental health clinicians with 127 consecutive individuals who presented with pure paracetamol overdoses to a large general hospital over 8 months, including asking about the source of the tablets and scoring the patients' acts on the Beck Suicide Intent scale (BSI). Patients were predominantly female (86%) and young (79% aged 12-24 years). Most had used paracetamol which was available in the home (77%). Those who purchased paracetamol for the act took double the number of tablets compared with those who used paracetamol available in the home (37 v. 18), had higher suicidal intent (mean BSI: 11 v. 7) and more often required treatment with N-acetyl cysteine (71% v. 43%). These results highlight the need for safer home storage of paracetamol and consideration of reducing pack size limits on paracetamol that can be purchased.},
}

@article {pmid39299599,
year = {2024},
author = {da Silva, AM and Murillo, DM and Anbumani, S and von Zuben, AA and Cavalli, A and Obata, HT and Fischer, ER and de Souza E Silva, M and Bakkers, E and Souza, AA and Carvalho, HF and Cotta, MA},
title = {N-acetylcysteine effects on extracellular polymeric substances of Xylella fastidiosa: A spatiotemporal investigation with implications for biofilm disruption.},
journal = {International journal of antimicrobial agents},
volume = {64},
number = {5},
pages = {107340},
doi = {10.1016/j.ijantimicag.2024.107340},
pmid = {39299599},
issn = {1872-7913},
mesh = {*Biofilms/drug effects ; *Xylella/drug effects/physiology ; *Acetylcysteine/pharmacology ; *Extracellular Polymeric Substance Matrix/drug effects/metabolism ; Bacterial Adhesion/drug effects ; Anti-Bacterial Agents/pharmacology ; Spatio-Temporal Analysis ; },
abstract = {BACKGROUND: The matrix of extracellular polymeric substances (EPS) present in biofilms greatly amplifies the problem of bacterial infections, protecting bacteria against antimicrobial treatments and eventually leading to bacterial resistance. The need for alternative treatments that destroy the EPS matrix becomes evident. N-acetylcysteine (NAC) is one option that presents diverse effects against bacteria; however, the different mechanisms of action of NAC in biofilms have yet to be elucidated.

OBJECTIVES: In this work, we performed microscopy studies at micro and nano scales to address the effects of NAC at single cell level and early-stage biofilms of the Xylella fastidiosa phytopathogen.

METHODS: We show the physical effects of NAC on the adhesion surface and the different types of EPS, as well as the mechanical response of individual bacteria to NAC concentrations between 2 and 20 mg/mL.

RESULTS: NAC modified the conditioning film on the substrate, broke down the soluble EPS, resulting in the release of adherent bacteria, decreased the volume of loosely bound EPS, and disrupted the biofilm matrix. Tightly bound EPS suffered structural alterations despite no solid evidence of its removal. In addition, bacterial force measurements upon NAC action performed with InP nanowire arrays showed an enhanced momentum transfer to the nanowires due to increased cell mobility resulting from EPS removal.

CONCLUSIONS: Our results clearly show that conditioning film and soluble EPS play a key role in cell adhesion control and that NAC alters EPS structure, providing solid evidence that NAC actuates mainly on EPS removal, both at single cell and biofilm levels.},
}

*Biofilms/drug effects
*Xylella/drug effects/physiology
*Acetylcysteine/pharmacology
*Extracellular Polymeric Substance Matrix/drug effects/metabolism
Bacterial Adhesion/drug effects
Anti-Bacterial Agents/pharmacology
Spatio-Temporal Analysis

@article {pmid39301637,
year = {2024},
author = {Jin, J and Nan, J and Si, Y and Chen, X and Wang, H and Wang, X and Huang, J and Guo, T},
title = {Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway.},
journal = {Molecular medicine reports},
volume = {30},
number = {5},
pages = {},
pmid = {39301637},
issn = {1791-3004},
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; Animals ; *Lung Neoplasms/drug therapy/metabolism/pathology ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System/drug effects ; Mice ; A549 Cells ; *Apoptosis/drug effects ; Xenograft Model Antitumor Assays ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Ferroptosis/drug effects ; Mice, Nude ; Antineoplastic Agents/pharmacology/therapeutic use ; },
abstract = {Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl‑2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z‑VAD‑FMK (an apoptosis inhibitor), ferrostatin‑1 (ferroptosis inhibitor) and N‑acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N‑acetylcysteine) treatment notably inhibited the rabdoternin E‑stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis‑related proteins (including Ki67, Bcl‑2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF‑7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.},
}

Humans
*Reactive Oxygen Species/metabolism
Animals
*Lung Neoplasms/drug therapy/metabolism/pathology
*p38 Mitogen-Activated Protein Kinases/metabolism
*MAP Kinase Signaling System/drug effects
Mice
A549 Cells
*Apoptosis/drug effects
Xenograft Model Antitumor Assays
Cell Proliferation/drug effects
Cell Line, Tumor
Ferroptosis/drug effects
Mice, Nude
Antineoplastic Agents/pharmacology/therapeutic use

@article {pmid39302378,
year = {2024},
author = {Park, J and Oh, JP and Ku, K and Jin, Y and Kim, EJ and Lee, JH},
title = {Preventing Donepezil-Induced Adverse Effects Through N-acetylcysteine Co-Administration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {101},
number = {4},
pages = {1281-1292},
doi = {10.3233/JAD-240709},
pmid = {39302378},
issn = {1875-8908},
mesh = {*Donepezil/pharmacology ; Animals ; *Acetylcysteine/pharmacology ; *Rats, Sprague-Dawley ; Male ; *Cholinesterase Inhibitors/pharmacology ; Female ; Rats ; *Reactive Oxygen Species/metabolism ; Calcium/metabolism ; Indans/pharmacology ; Piperidines/pharmacology ; },
abstract = {BACKGROUND: Drug-induced adverse symptoms affect patients' quality of life (QoL) during treatment. Understanding the underlying mechanisms of drug-induced adverse effects could help prevent them. As current drugs have limited effects in halting the progress of Alzheimer's disease (AD), patients are required to take these drugs over a long period. The main obstacles to long-term compliance are drug-elicited side effects that deteriorate patient QoL.

OBJECTIVE: Donepezil, the most popular acetylcholinesterase inhibitor (AChEI) drug for AD, induces various side effects, especially at high doses. This study aimed to identify a drug that can attenuate the side effects of donepezil and investigate the underlying mechanisms.

METHODS: Five-week-old Sprague-Dawley rats received daily oral donepezil and N-acetylcysteine (NAC) for four weeks. General symptoms following administration were monitored daily to address drug-related adverse effects. Cytosolic calcium influx and generation of reactive oxygen species (ROS) after drug treatment were measured in vitro using C2C12 myotubes.

RESULTS: High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with NAC. NAC significantly reduced both acute and chronic muscle-related symptoms caused by donepezil. Additionally, in vitro studies showed that high-dose donepezil increased ROS and intracellular calcium ([Ca2+]i) levels in muscle cells, contributing to these adverse effects. NAC co-treatment dramatically reduced ROS and [Ca2+]i levels in muscle cells.

CONCLUSIONS: Combined treatment with NAC effectively diminishes the adverse effects elicited by donepezil by regulating ROS and [Ca2+]i levels in the skeletal muscle, which could contribute to improving donepezil treatment in patients.},
}

*Donepezil/pharmacology
Animals
*Acetylcysteine/pharmacology
*Rats, Sprague-Dawley
Male
*Cholinesterase Inhibitors/pharmacology
Female
Rats
*Reactive Oxygen Species/metabolism
Calcium/metabolism
Indans/pharmacology
Piperidines/pharmacology

@article {pmid39309000,
year = {2024},
author = {Cuocina, M and Aiello, G and Cutrufelli, P and Rampello, M and Rapisarda, L and Rodolico, A and Cantarella, G and Signorelli, MS and Bernardini, R},
title = {Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1462612},
pmid = {39309000},
issn = {1663-9812},
abstract = {BACKGROUND: N-acetyl cysteine (NAC) appears promising as a treatment in patients with substance use disorder (SUD) as it helps rebalance glutamate levels in the central nervous system (CNS). Basal concentrations of glutamate are indeed reduced in SUD patients but increased during craving.

MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether NAC reduce craving rating as compared to a placebo in SUD patients. Secondary outcomes were withdrawal symptoms (WS), side effects (SE) and drop-outs. Estimates are presented as standardized mean differences (SMD) or risk ratio (RR) with 95% confidence interval (CI).

RESULTS: Eleven RCTs were included. NAC reduced craving rating (SMD -0.61 (-1.17, -0.06), p = 0.03, I2 = 85%), with no differences in the subgroup analysis according to the drug addiction (alcohol, cocaine, poly-drugs, amphetamine, nicotine) (p = 0.98). Among the secondary outcomes, for WS data showed no significant difference between groups (SMD -0.18 (-0.43, 0.08), p = 0.17); for SE no substantial difference was observed between the two treatment groups (RR = 1.06 (0.89-1.27), p = 0.52, I2 = 0%); for dropouts the results are in favor of the placebo but no statistically significant (RR 1.17 (0.85, 1.61), p = 0.34; I2 = 0%).

CONCLUSION: NAC seem to reduce craving rating in SUD patients, but evidence is weak. More studies are needed to confirm this finding.},
}

@article {pmid39312076,
year = {2024},
author = {Xue, Y and Bian, H and Bai, S and Bao, Z and Wang, L and Wang, S and Zhao, B and Wu, X and Chen, Y},
title = {N-acetylcysteine mitigates oxidative damage to the ovary in D-galactose-induced ovarian failure in rabbits.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {1008},
pmid = {39312076},
issn = {1573-4978},
support = {CARS-43-A-1//China Agriculture Research System of MOF and MARA/ ; 2022//Qing Lan Project of Yangzhou university/ ; },
mesh = {Animals ; Rabbits ; Female ; *Acetylcysteine/pharmacology ; *Galactose/adverse effects/pharmacology ; *Oxidative Stress/drug effects ; *Ovary/drug effects/metabolism/pathology ; Primary Ovarian Insufficiency/chemically induced/metabolism/pathology ; Granulosa Cells/metabolism/drug effects ; Antioxidants/pharmacology/metabolism ; Superoxide Dismutase/metabolism ; Glutathione/metabolism ; Catalase/metabolism ; Disease Models, Animal ; },
abstract = {BACKGROUND: Oxidative damage to the ovaries is the primary cause of impaired reproductive functions in female animals. This study aimed to investigate the protective role of N-Acetyl-L-cysteine (NAC) in reducing oxidative damage in the ovaries of female rabbits.

METHODS AND RESULTS: Female rabbit ovaries were treated in vitro with varying concentrations of D-galactose (D-gal): 0, 5, 10, and 15 mg/mL, and it was found that 10 mg/mL D-gal significantly disrupted follicular structures, causing disarray in granulosa cell arrangements and significantly reducing T-SOD and GSH levels (p < 0.01). Consequently, we selected 10 mg/mL D-gal to establish an ovarian failure model. These models were treated with multiple doses of NAC (0, 0.1, 0.3, 0.5 mg/mL). The results revealed that the disruption in granulosa cell arrangement caused by 10 mg/mL D-gal was effectively alleviated by 0.1 mg/mL NAC compared to the D-gal treatment group. Furthermore, 10 mg/mL D-gal significantly (p < 0.01) reduced GSH, T-SOD, and catalase (CAT) levels in the ovaries. However, 0.1 mg/mL NAC effectively (p < 0.01) suppressed these adverse effects. Moreover, the current results showed that 10 mg/mL D-gal alone significantly (p < 0.01) downregulated the expression of Nrf2, GPX, PRDX4, GSR, SOD1, and TAF4B, whereas 0.1 mg/mL NAC counteracted these suppressive effects (p < 0.01).

CONCLUSIONS: It could be concluded that NAC may delay ovarian failure by reducing D-gal-induced ovarian oxidative damage in female rabbit, suggested NAC could be a promising therapeutic agent for protecting against ovarian failure and potentially delaying ovarian failure in female rabbits.},
}

Animals
Rabbits
Female
*Acetylcysteine/pharmacology
*Galactose/adverse effects/pharmacology
*Oxidative Stress/drug effects
*Ovary/drug effects/metabolism/pathology
Primary Ovarian Insufficiency/chemically induced/metabolism/pathology
Granulosa Cells/metabolism/drug effects
Antioxidants/pharmacology/metabolism
Superoxide Dismutase/metabolism
Glutathione/metabolism
Catalase/metabolism
Disease Models, Animal

@article {pmid39312385,
year = {2024},
author = {Dinç, M and Soydemir, ÖC},
title = {Efficacy of N-acetylcysteine in reducing inflammation and oxidative stress to prevent complex regional pain syndrome type 1.},
journal = {Medicine},
volume = {103},
number = {38},
pages = {e39742},
pmid = {39312385},
issn = {1536-5964},
mesh = {Humans ; *Acetylcysteine/therapeutic use ; Female ; Male ; *Oxidative Stress/drug effects ; Middle Aged ; *Reflex Sympathetic Dystrophy/drug therapy/blood ; Retrospective Studies ; Aged ; Inflammation/blood/prevention & control ; Radius Fractures ; Antioxidants/therapeutic use ; Biomarkers/blood ; Cytokines/blood ; Tumor Necrosis Factor-alpha/blood ; },
abstract = {This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) in preventing complex regional pain syndrome type 1 (CRPS-1) by reducing proinflammatory cytokines and oxidative stress markers in patients with distal radius fractures. A retrospective single-center study at Bursa City Hospital involves patients over 50 years of age with distal radius fractures treated between January 2021 and December 2023. A total of 60 patients (mean age, 62.8 ± 5.1 years; 26 males and 34 females) were analyzed. Patients were divided into 2 groups: the NAC group (31 patients receiving 600-mg NAC daily for 3 months) and the control group (29 patients with no prophylactic medication). CRPS-1 diagnosis was based on Budapest criteria during multiple follow-up visits. Serum levels of interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha (TNF-α), total oxidant status (TOS), and total antioxidant status (TAS) were measured at baseline and study end point. CRPS-1 positive patients had significantly higher levels of IL-6, TNF-α, and IL-1 (P < .001 for all), higher TOS (P < .001) and oxidative stress index (P < .001), and lower TAS (P < .001) compared with CRPS-1 negatives. The incidence of CRPS-1 was significantly lower in the NAC group (9.7%) compared with the control group (31.0%; P = .039). Logistic regression indicated a 78% reduction in CRPS-1 odds ratio with NAC treatment (odds ratio, 0.219 [95% confidence interval, 0.053-0.895]; P = .0322). NAC significantly reduced end-point levels and changes in IL-6 (P < .001), TNF-α (P < .001), and IL-1 (P = .038) and improved oxidative stress markers, showing higher TAS (P < .001), lower TOS (P < .001), and oxidative stress index (P < .001) compared with controls. NAC significantly reduced the risk of developing CRPS-1 by decreasing levels of proinflammatory cytokines and oxidative stress. This study highlights NAC's potential as a preventive treatment for CRPS-1 and emphasizes the importance of early intervention.},
}

Humans
*Acetylcysteine/therapeutic use
Female
Male
*Oxidative Stress/drug effects
Middle Aged
*Reflex Sympathetic Dystrophy/drug therapy/blood
Retrospective Studies
Aged
Inflammation/blood/prevention & control
Radius Fractures
Antioxidants/therapeutic use
Biomarkers/blood
Cytokines/blood
Tumor Necrosis Factor-alpha/blood

@article {pmid39313073,
year = {2025},
author = {Fort, TD and Azuma, MC and Laux, DA and Cain, ME},
title = {Environmental enrichment and sex, but not n-acetylcysteine, alter extended-access amphetamine self-administration and cue-seeking.},
journal = {Behavioural brain research},
volume = {476},
number = {},
pages = {115261},
pmid = {39313073},
issn = {1872-7549},
support = {P20 GM113109/GM/NIGMS NIH HHS/United States ; R15 DA035435/DA/NIDA NIH HHS/United States ; },
mesh = {Animals ; *Cues ; Male ; Female ; *Amphetamine/pharmacology/administration & dosage ; *Self Administration ; *Acetylcysteine/pharmacology/administration & dosage ; *Rats, Sprague-Dawley ; *Central Nervous System Stimulants/pharmacology/administration & dosage ; *Environment ; Drug-Seeking Behavior/drug effects/physiology ; Rats ; Nucleus Accumbens/drug effects/metabolism ; Astrocytes/drug effects/metabolism ; Sex Characteristics ; Prefrontal Cortex/drug effects/metabolism ; },
abstract = {There are no approved therapeutics for psychostimulant use and recurrence of psychostimulant use. However, in preclinical rodent models environmental enrichment can decrease psychostimulant self-administration of low unit doses and cue-induced amphetamine seeking. We have previously demonstrated that glutamate-dependent therapeutics are able to alter amphetamine seeking to amphetamine-associated cues only in enriched rats. In the current experiment, we will determine if enrichment can attenuate responding and cue-induced amphetamine seeking during extended access to a high dose of intravenous amphetamine. We will also determine if N-acetylcysteine (NAC), a glutamate dependent therapeutic, can attenuate amphetamine seeking in differentially reared rats. Female and male Sprague-Dawley rats were reared in enriched, isolated, or standard conditions from postnatal day 21-51. Rats were trained to self-administer intravenous amphetamine (0.1 mg/kg/infusion) during twelve 6-hour sessions. During the abstinence period, NAC (100 mg/kg) or saline was administered daily. Following a cue-induced amphetamine-seeking test, astrocyte densities within regions of the medial prefrontal cortex (mPFC) and nucleus accumbens (ACb) were quantified using immunohistochemistry. Environmental enrichment decreased responding for amphetamine and during the cue-induced amphetamine-seeking test. NAC did not attenuate cue-induced amphetamine seeking or alter astrocyte density. Across all groups, female rats self-administered less amphetamine but responded more during cue-induced amphetamine seeking than male rats. While amphetamine increased astrocyte densities within the ACb and mPFC, it did not alter mPFC astrocyte densities in female rats. The results suggest that enrichment can attenuate responding during extended access to a high dose of amphetamine and the associated cues. Sex alters amphetamine-induced changes to astrocyte densities in a regionally specific matter.},
}

Animals
*Cues
Male
Female
*Amphetamine/pharmacology/administration & dosage
*Self Administration
*Acetylcysteine/pharmacology/administration & dosage
*Rats, Sprague-Dawley
*Central Nervous System Stimulants/pharmacology/administration & dosage
*Environment
Drug-Seeking Behavior/drug effects/physiology
Rats
Nucleus Accumbens/drug effects/metabolism
Astrocytes/drug effects/metabolism
Sex Characteristics
Prefrontal Cortex/drug effects/metabolism

@article {pmid39319193,
year = {2024},
author = {Attiq, A and Afzal, S and Wahab, HA and Ahmad, W and Kandeel, M and Almofti, YA and Alameen, AO and Wu, YS},
title = {Cytokine Storm-Induced Thyroid Dysfunction in COVID-19: Insights into Pathogenesis and Therapeutic Approaches.},
journal = {Drug design, development and therapy},
volume = {18},
number = {},
pages = {4215-4240},
pmid = {39319193},
issn = {1177-8881},
mesh = {Humans ; *COVID-19/complications ; *Cytokine Release Syndrome/drug therapy/etiology ; *SARS-CoV-2 ; *COVID-19 Drug Treatment ; Cytokines/metabolism ; Thyroid Diseases/drug therapy/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Thyroid Gland/metabolism/physiopathology ; },
abstract = {Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in the renin-angiotensin system (RAS). On thyroid follicular cells, ACE2R allows SARS-CoV-2 to invade the thyroid gland, impose cytopathic effects and produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, and enlarged, inflamed thyroid gland in COVID-19 patients. Further damage is perpetuated by the sudden bursts of pro-inflammatory cytokines, which is suggestive of a life-threatening syndrome known as a "cytokine storm". IL-1β, IL-6, IFN-γ, and TNF-α are identified as the key orchestrators of the cytokine storm. These inflammatory mediators upregulate transcriptional turnover of nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK), paving the pathway for cytokine storm-induced thyroid dysfunctions including euthyroid sick syndrome, autoimmune thyroid diseases, and thyrotoxicosis in COVID-19 patients. Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) and N-acetyl-cysteine have demonstrated effectiveness in terms of attenuating the severity and frequency of cytokine storm-induced thyroid dysfunctions, morbidity and mortality in severe COVID-19 patients. Here, we review the pathogenesis of cytokine storms and the mechanisms and pathways that establish the connection between thyroid disorder and COVID-19. Moreover, cross-talk interactions of signalling pathways and therapeutic strategies to address COVID-19-associated thyroid diseases are also discussed herein.},
}

Humans
*COVID-19/complications
*Cytokine Release Syndrome/drug therapy/etiology
*SARS-CoV-2
*COVID-19 Drug Treatment
Cytokines/metabolism
Thyroid Diseases/drug therapy/metabolism
Angiotensin-Converting Enzyme 2/metabolism
Thyroid Gland/metabolism/physiopathology

@article {pmid39331828,
year = {2025},
author = {Moraes, LGDS and Oliveira, VC and Macedo, AP and Freiria de Oliveira, CA and Watanabe, E and Pagnano, VO},
title = {Enhancing Removable Partial Denture Hygiene: Investigating Mucolytic Agents and Biocides for Disrupting Biofilms and Improving Antimicrobial Efficacy.},
journal = {The International journal of prosthodontics},
volume = {38},
number = {5},
pages = {559-569},
doi = {10.11607/ijp.9133},
pmid = {39331828},
issn = {1942-4426},
mesh = {*Biofilms/drug effects ; Candida albicans/drug effects ; Streptococcus mutans/drug effects ; Cetylpyridinium/pharmacology ; *Denture, Partial, Removable/microbiology ; Peracetic Acid/pharmacology ; Staphylococcus aureus/drug effects ; Acetylcysteine/pharmacology ; Candida glabrata/drug effects ; Acrylic Resins/chemistry ; *Denture Cleansers/pharmacology ; *Anti-Infective Agents/pharmacology ; Surface Properties ; },
abstract = {PURPOSE: To evaluate the antibiofilm action of 2.5 mg/mL peracetic acid (PA), 0.5 mg/mL cetylpyridinium chloride (CPC), and 160 mg/mL N-acetylcysteine (NAC) against multispecies biofilm of Streptococcus mutans, Staphylococcus aureus, Candida albicans, and Candida glabrata developed on surfaces of heat-polymerizing acrylic resin (AR) and cobalt-chromium (Co-Cr) alloy.

MATERIALS AND METHODS: A multispecies biofilm was grown on the surface of AR and Co-Cr specimens (Ø 12 × 3 mm). After biofilm maturation, the specimens were immersed in experimental solutions and evaluated through biofilm viability (CFU; n = 9), biofilm metabolic activity (XTT; n = 9), biofilm-covered areas (live/dead; n = 2), effects on the extracellular polymeric substance (EPS; n = 2), and biofilm morphology (n = 1). Data were analyzed by ANOVA and Tukey post-hoc test or Kruskal-Wallis followed by Dunn post-hoc test (α = .05).

RESULTS: Overall, all evaluated solutions impacted biofilm viability. PA presented wider activity by reducing CFU of all microorganisms on both surfaces, XTT (P < .001) and live/dead (P < .001). NAC had a notorious effect in reducing the viability of bacteria without affecting the yeasts. NAC reduced XTT on AR (P = .006) and Co-Cr (P = .003) but did not reduce the aggregated biofilm layer. CPC had a distinct effect, being most effective in reducing CFU on AR compared to the Co-Cr surface. However, it did not influence XTT or the amount of residual aggregated biofilm.

CONCLUSIONS: PA provided the greatest antibiofilm action, while CPC and NAC showed intermediate action. Nonetheless, no solution was able to completely remove the biofilm adhered to the surfaces of heat-polymerizing AR and Co-Cr alloy.},
}

*Biofilms/drug effects
Candida albicans/drug effects
Streptococcus mutans/drug effects
Cetylpyridinium/pharmacology
*Denture, Partial, Removable/microbiology
Peracetic Acid/pharmacology
Staphylococcus aureus/drug effects
Acetylcysteine/pharmacology
Candida glabrata/drug effects
Acrylic Resins/chemistry
*Denture Cleansers/pharmacology
*Anti-Infective Agents/pharmacology
Surface Properties

@article {pmid39332540,
year = {2024},
author = {Yao, Z and Xue, K and Chen, J and Zhang, Y and Zhang, G and Zheng, Z and Li, Z and Li, Z and Wang, F and Sun, X and Shen, L and Mao, C and Lin, C},
title = {Biliverdin improved angiogenesis and suppressed apoptosis via PI3K/Akt-mediated Nrf2 antioxidant system to promote ischemic flap survival.},
journal = {Free radical biology & medicine},
volume = {225},
number = {},
pages = {35-52},
doi = {10.1016/j.freeradbiomed.2024.09.042},
pmid = {39332540},
issn = {1873-4596},
mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; Humans ; *Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; *Apoptosis/drug effects ; Animals ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Proto-Oncogene Proteins c-akt/metabolism ; *Signal Transduction/drug effects ; *Neovascularization, Physiologic/drug effects ; *Surgical Flaps ; *Ischemia/metabolism/drug therapy/pathology ; *Biliverdine/metabolism/pharmacology ; *Antioxidants/pharmacology ; Hydrogen Peroxide/metabolism ; Mice ; Reactive Oxygen Species/metabolism ; Cell Proliferation/drug effects ; Oxidative Stress/drug effects ; Male ; Angiogenesis ; },
abstract = {Plastic and reconstructive surgeons frequently utilize random skin flap transplantation to repair skin defects. However, the procedure carries a substantial risk of necrosis. Previous research has suggested that Biliverdin (Bv), the main component of Calculus Bovis, possessed potent anti-ischemic properties, making it a potential therapeutic agent for skin flap survival. Hence, in this study, the potential of Bv in promoting flap survival has been comprehensively investigated. Network pharmacology analysis revealed that the pharmacological effects of Bv on ischemic diseases may be attributed to its modulation of various signaling molecules, including the PI3K-Akt pathway. In vitro results demonstrated that Bv treatment significantly promoted angiogenesis in human umbilical vein endothelial cells (HUVEC), even in the presence of H2O2. This was evident by the increased cell proliferation, enhanced migration, and improved tube formation. Bv also effectively attenuated the intracellular generation of reactive oxygen species (ROS) induced by H2O2, which was achieved by suppressing mitochondrial ROS production through the PI3K/Akt-mediated activation of Nrf2/HO-1 signaling pathway. Consequently, Bv treatment led to a significant reduction in apoptosis and an increase in cell viability of HUVEC. Furthermore, in vivo experiment demonstrated that Bv treatment vastly elevated flap survival through enhancing angiogenesis while decreasing oxidative stress and apoptosis, which was comparable to the results of positive control of N-acetylcysteine (Nac). In conclusion, this study not only established a solid foundation for future study on therapeutic potential of Bv, but also proposed a promising treatment approach for enhancing the success rate of flap transplants and other ischemic-related tissue repair.},
}

*NF-E2-Related Factor 2/metabolism/genetics
Humans
*Human Umbilical Vein Endothelial Cells/drug effects/metabolism
*Apoptosis/drug effects
Animals
*Phosphatidylinositol 3-Kinases/metabolism/genetics
*Proto-Oncogene Proteins c-akt/metabolism
*Signal Transduction/drug effects
*Neovascularization, Physiologic/drug effects
*Surgical Flaps
*Ischemia/metabolism/drug therapy/pathology
*Biliverdine/metabolism/pharmacology
*Antioxidants/pharmacology
Hydrogen Peroxide/metabolism
Mice
Reactive Oxygen Species/metabolism
Cell Proliferation/drug effects
Oxidative Stress/drug effects
Male
Angiogenesis

@article {pmid39337344,
year = {2024},
author = {Morabito, C and Di Sinno, N and Mariggiò, MA and Guarnieri, S},
title = {Impact of Extremely Low-Frequency Electromagnetic Fields on Skeletal Muscle of Sedentary Adult Mice: A Pilot Study.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337344},
issn = {1422-0067},
mesh = {Animals ; *Electromagnetic Fields/adverse effects ; Mice ; Male ; Pilot Projects ; *Muscle, Skeletal/metabolism/radiation effects ; *Oxidative Stress/radiation effects ; *Mice, Inbred C57BL ; *Superoxide Dismutase-1/metabolism ; Acetylcysteine/pharmacology ; Myosin Heavy Chains/metabolism ; Antioxidants/metabolism ; PAX7 Transcription Factor/metabolism ; Sedentary Behavior ; Muscle Strength/radiation effects ; Catalase/metabolism ; },
abstract = {Extremely low-frequency electromagnetic fields (ELF-EMFs) are ubiquitous in industrialized environments due to the continuous use of electrical devices. Our previous studies demonstrated that ELF-EMFs affect muscle cells by modulating oxidative stress and enhancing myogenesis. This pilot study investigated these effects on the skeletal muscles of sedentary adult mice, assessing physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplementation. Male C57BL/6 mice were exposed to ELF-EMFs (0.1 or 1.0 mT) for 1 h/day for up to 5 weeks and fed a standard diet without or with N-acetyl-cysteine (NAC). The results showed transient increases in muscle strength (after 2 weeks of exposure at 1.0 mT), potentially linked to muscle fiber recruitment and activation, revealed by higher PAX7 and myosin heavy chain (MyH) expression levels. After ELF-EMF exposure, oxidative status assessment revealed transient increases in the expression levels of SOD1 and catalase enzymes, in total antioxidant capacity, and in protein carbonyl levels, markers of oxidative damage. These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal muscle physiology and NAC supplementation partially mitigates these effects, highlighting the complex interactions between ELF-EMFs and antioxidant pathways in vivo. Further investigations on ELF-EMFs as a therapeutic modality for muscle health are necessary.},
}

Animals
*Electromagnetic Fields/adverse effects
Mice
Male
Pilot Projects
*Muscle, Skeletal/metabolism/radiation effects
*Oxidative Stress/radiation effects
*Mice, Inbred C57BL
*Superoxide Dismutase-1/metabolism
Acetylcysteine/pharmacology
Myosin Heavy Chains/metabolism
Antioxidants/metabolism
PAX7 Transcription Factor/metabolism
Sedentary Behavior
Muscle Strength/radiation effects
Catalase/metabolism

@article {pmid39337474,
year = {2024},
author = {Stachura, A and Sobczak, M and Kędra, K and Kopka, M and Kopka, K and Włodarski, PK},
title = {The Influence of N-Acetylcysteine-Enriched Hydrogels on Wound Healing in a Murine Model of Type II Diabetes Mellitus.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337474},
issn = {1422-0067},
support = {1MN/2/MG/N/20//Medical University of Warsaw/ ; },
mesh = {Animals ; *Acetylcysteine/pharmacology/administration & dosage ; *Hydrogels/chemistry ; *Wound Healing/drug effects ; Mice ; *Diabetes Mellitus, Type 2/drug therapy ; *Disease Models, Animal ; Skin/drug effects/pathology ; Male ; Cell Proliferation/drug effects ; Antioxidants/pharmacology ; Diabetes Mellitus, Experimental/drug therapy ; },
abstract = {Diabetes mellitus (DM) severely impairs skin wound healing capacity, yet few treatment options exist to enhance this process. N-acetylcysteine (NAC) is an antioxidant that improves cellular proliferation and enhances wound healing in healthy animals, yet its use in the context of type II DM has not been studied. The aim of our research was to investigate the effect of topically applied NAC-enriched hydrogels on wound healing in a leptin-deficient murine wound model. Four excisional wounds were created on the backs of 20 db/db mice and were subsequently treated with hydrogels containing NAC at concentrations of 5%, 10% and 20% or placebo (control). Healing was monitored for 28 days; photographs of the wounds were taken on every third day. Wound tissues were harvested on days 3, 7, 14 and 28 to undergo histological examinations. Wounds treated with 5% NAC showed improved wound closure speed accompanied by an increased dermal proliferation area on microscopic assessment compared with other groups. Higher concentrations of NAC failed to show a beneficial effect on wound healing. 5% NAC improved early stages of wound healing in a murine model of type II DM by increasing wound closure speed, likely mediated by improved dermal proliferation.},
}

Animals
*Acetylcysteine/pharmacology/administration & dosage
*Hydrogels/chemistry
*Wound Healing/drug effects
Mice
*Diabetes Mellitus, Type 2/drug therapy
*Disease Models, Animal
Skin/drug effects/pathology
Male
Cell Proliferation/drug effects
Antioxidants/pharmacology
Diabetes Mellitus, Experimental/drug therapy

@article {pmid39337681,
year = {2024},
author = {Zhang, M and Chai, ZH and Zhang, C and Chen, L},
title = {Unbalanced Expression of Structural Genes in Carotenoid Pathway Contributes to the Flower Color Formation of the Osmanthus Cultivar 'Yanzhi Hong'.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337681},
issn = {1422-0067},
support = {BK20200786//Natural Science Foundation of Jiangsu Province/ ; 2019M651839//China Postdoctoral Science Foundation/ ; CX2019029//Innovation Fund for Young Scholars of Nanjing Forestry University/ ; 32071782//National Natural Science Foundation of China/ ; },
mesh = {*Carotenoids/metabolism ; *Flowers/genetics/metabolism/growth & development ; *Gene Expression Regulation, Plant ; *Pigmentation/genetics ; *Oleaceae/genetics/metabolism/growth & development ; Plant Proteins/genetics/metabolism ; Gene Expression Profiling/methods ; },
abstract = {Carotenoids are important natural pigments that are responsible for the fruit and flower colors of many plants. The composition and content of carotenoid can greatly influence the color phenotype of plants. However, the regulatory mechanism underling the divergent behaviors of carotenoid accumulation, especially in flower, remains unclear. In this study, a new cultivar Osmanthus fragrans 'Yanzhi Hong' was used to study the regulation of carotenoid pigmentation in flower. Liquid chromatograph-mass spectrometer (LC-MS) analysis showed that β-carotene, phytoene, lycopene, γ-carotene, and lutein were the top five pigments enriched in the petals of 'Yanzhi Hong'. Through transcriptome analysis, we found that the expression of the structural genes in carotenoid pathway was imbalanced: most of the structural genes responsible for lycopene biosynthesis were highly expressed throughout the flower developmental stages, while those for lycopene metabolism kept at a relatively lower level. The downregulation of LYCE, especially at the late developmental stages, suppressed the conversion from lycopene to α-carotene but promoted the accumulation of β-carotene, which had great effect on the carotenoid composition of 'Yanzhi Hong'. Ethylene response factor (ERF), WRKY, basic helix-loop-helix (bHLH), v-myb avian myeloblastosis viral oncogene homolog (MYB), N-Acetylcysteine (NAC), auxin response factor (ARF), and other transcription factors (TFs) have participated in the flower color regulation of 'Yanzhi Hong', which formed co-expression networks with the structural genes and functioned in multiple links of the carotenoid pathway. The results suggested that the cyclization of lycopene is a key link in determining flower color. The modification of the related TFs will break the expression balance between the upstream and downstream genes and greatly influence the carotenoid profile in flowers, which can be further used for creating colorful plant germplasms.},
}

*Carotenoids/metabolism
*Flowers/genetics/metabolism/growth & development
*Gene Expression Regulation, Plant
*Pigmentation/genetics
*Oleaceae/genetics/metabolism/growth & development
Plant Proteins/genetics/metabolism
Gene Expression Profiling/methods

@article {pmid39339161,
year = {2024},
author = {Alam, MI and Paget, T and Moosa, NY and Alghurairy, H and Elkordy, AA},
title = {Liposomal Drug Delivery against Helicobacter pylori Using Furazolidone and N-Acetyl Cysteine in Augmented Therapy.},
journal = {Pharmaceutics},
volume = {16},
number = {9},
pages = {},
pmid = {39339161},
issn = {1999-4923},
abstract = {Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world's population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy.},
}

@article {pmid39339978,
year = {2024},
author = {Wang, Y and Luan, T and Wang, L and Feng, D and Dong, Y and Li, S and Yang, H and Chen, Y and Fei, Y and Lin, L and Pan, J and Zhong, Z and Zhao, W},
title = {N-Acetylcysteine Inhibits Coxsackievirus B3 Replication by Downregulating Eukaryotic Translation Elongation Factor 1 Alpha 1.},
journal = {Viruses},
volume = {16},
number = {9},
pages = {},
pmid = {39339978},
issn = {1999-4915},
mesh = {Animals ; Humans ; Male ; Mice ; *Acetylcysteine/pharmacology ; Antiviral Agents/pharmacology ; Cell Line ; *Coxsackievirus Infections/drug therapy/virology ; *Down-Regulation/drug effects ; *Enterovirus B, Human/drug effects/physiology ; Myocarditis/virology/drug therapy ; *Peptide Elongation Factor 1/metabolism/genetics ; *Virus Replication/drug effects ; },
abstract = {Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.},
}

Animals
Humans
Male
Mice
*Acetylcysteine/pharmacology
Antiviral Agents/pharmacology
Cell Line
*Coxsackievirus Infections/drug therapy/virology
*Down-Regulation/drug effects
*Enterovirus B, Human/drug effects/physiology
Myocarditis/virology/drug therapy
*Peptide Elongation Factor 1/metabolism/genetics
*Virus Replication/drug effects

@article {pmid39342748,
year = {2024},
author = {Zhang, S and Wang, D and Ding, Y and Li, Y and Wang, Y and Zeng, J},
title = {Inhibition of calpain reduces oxidative stress and attenuates pyroptosis and ferroptosis in Clostridium perfringens Beta-1 toxin-induced macrophages.},
journal = {Microbiological research},
volume = {289},
number = {},
pages = {127916},
doi = {10.1016/j.micres.2024.127916},
pmid = {39342748},
issn = {1618-0623},
mesh = {*Pyroptosis/drug effects ; *Ferroptosis/drug effects ; *Macrophages/drug effects/metabolism ; *Oxidative Stress/drug effects ; *Reactive Oxygen Species/metabolism ; *Bacterial Toxins/metabolism/toxicity ; Mice ; Animals ; *Calpain/metabolism ; Humans ; Clostridium perfringens/drug effects/metabolism ; Hydrogen Peroxide/metabolism ; Mitochondrial Proton-Translocating ATPases/metabolism ; RAW 264.7 Cells ; Acetylcysteine/pharmacology/metabolism ; Inflammation/metabolism ; },
abstract = {Clostridium perfringens Beta-1 toxin (CPB1) is a lethal toxin, which can lead to necrotic enteritis, but the pathological mechanism has not been elucidated. We investigated whether reactive oxygen species (ROS) participated in CPB1-induced pyroptosis and ferroptosis, and investigated the effects of calpain on CPB1-induced oxidative stress and inflammation. Scavenging ROS by N-Acetyl-L cysteine (NAC) led to the reduction of ROS, inhibited the death of macrophages, cytoplasmic swelling and membrane rupture, the expression of pyroptosis-related proteins and proinflammatory factor, while increased the expression of anti-inflammatory factors in cells treated with rCPB1. Adenosine triphosphate (ATP) synthase, H[+] transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1) was identified specifically interact with rCPB1. Silencing ATP5A1 inhibited accumulation of ATP and ROS, leaded to less cytoplasmic swelling and membrane rupture, attenuated pyroptosis and inflammation in rCPB1-treated cells. We also found that rCPB1 induces ferroptosis in macrophages, and the level of ferroptosis was similar with H2O2. Of note, H2O2 is a major ROS source, indicated that ROS production may play a major role in the regulation of ferroptosis in macrophages treated with rCPB1. This finding was further corroborated in rCPB1- induced human acute monocytic leukemia cells, which were treated with NAC. In addition, the inhibition of ferroptosis using liproxstatin-1 inhibited the shriveled mitochondrial morphology, increased the expression of glutathione peroxidase 4, nicotinamide adenine dinucleotide (phosphate) hydrogen: quinone oxidoreductase 1 and cysteine/glutamic acid reverse transport solute carrier family 7 members 11, decreased the expression of heme oxygenase 1, nuclear receptor coactivator 4 and transferrin receptor proteins, reduced malondialdehyde and lipid peroxidation levels, and increased intracellular L-glutathione levels in cells treated with rCPB1. Furthermore, calpain inhibitor PD151746 was used to investigate how pyroptosis and ferroptosis were involved simultaneously in rCPB1-treated macrophages. We showed that PD151746 inhibited ATP and ROS production, reversed the representative pyroptosis/ferroptosis indicators and subsequently reduced inflammation. The above findings indicate that rCPB1 might lead to macrophage pyroptosis and ferroptosis through the large and sustained increase in intracellular calpain and oxidative stress, further lead to inflammation.},
}

*Pyroptosis/drug effects
*Ferroptosis/drug effects
*Macrophages/drug effects/metabolism
*Oxidative Stress/drug effects
*Reactive Oxygen Species/metabolism
*Bacterial Toxins/metabolism/toxicity
Mice
Animals
*Calpain/metabolism
Humans
Clostridium perfringens/drug effects/metabolism
Hydrogen Peroxide/metabolism
Mitochondrial Proton-Translocating ATPases/metabolism
RAW 264.7 Cells
Acetylcysteine/pharmacology/metabolism
Inflammation/metabolism

@article {pmid39348347,
year = {2024},
author = {Komal, W and Fatima, S and Minahal, Q and Liaqat, R and Hussain, AS},
title = {Assessing the effects of N-acetyl cysteine on growth, antioxidant and immune response in tilapia (Oreochromis niloticus) under different regimes of stocking densities.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0307212},
pmid = {39348347},
issn = {1932-6203},
mesh = {Animals ; *Antioxidants/metabolism/pharmacology ; *Acetylcysteine/pharmacology ; *Dietary Supplements ; Hydrocortisone/metabolism ; Cichlids/growth & development/immunology/metabolism ; Superoxide Dismutase/metabolism ; Animal Feed/analysis ; Catalase/metabolism ; Tilapia/growth & development/immunology/metabolism ; Aquaculture/methods ; Glutathione Peroxidase/metabolism ; },
abstract = {The study investigated the impact of N-acetyl cysteine on growth, immune response, and antioxidant activity in tilapia (Oreochromis niloticus). Fish were reared at three densities (1.50, 3.00, and 4.50 kg/m3) with four levels of N-acetyl cysteine supplementation (0, 2, 4, and 6 mg/kg) over 60 days. Better growth was observed at low density, but at all densities, fish fed the highest N-acetyl cysteine level (6 mg/kg) showed improved growth. Chemical composition of fish and activity of amylase, lipase and protease in all treatments were noted to be insignificant. The levels of antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and cortisol in HD treatments were high as compared to LD and MD treatment. However, fish fed with N3 diet in each density treatment showed the lowest level of antioxidant enzymes as well as cortisol. Similarly, the levels of malondialdehyde were noted to be high at HD treatments as compared to that in LD and MD. Its levels were lower in fish fed with N3 diets in all density treatments. Expression of somatostatins-1 did not increase in MD and HD treatments in response to high stocking density when compared with LD treatment. However, pro-opiomelanocortin-α level was reduced after N3 diet in HD treatment and interleukin 1-β expression increased after N3 supplement in HD treatment. In conclusion, N-acetyl cysteine supplementation improved growth and antioxidant response in tilapia. The most optimum dose of N-acetyl cysteine was noted to be 6 mg/kg at high stocking, suggesting the potential role of this nutraceutical in tilapia intensive culture.},
}

Animals
*Antioxidants/metabolism/pharmacology
*Acetylcysteine/pharmacology
*Dietary Supplements
Hydrocortisone/metabolism
Cichlids/growth & development/immunology/metabolism
Superoxide Dismutase/metabolism
Animal Feed/analysis
Catalase/metabolism
Tilapia/growth & development/immunology/metabolism
Aquaculture/methods
Glutathione Peroxidase/metabolism

@article {pmid39349423,
year = {2024},
author = {Wang, SH and Lee, DS and Kim, TH and Kim, JE and Kang, TC},
title = {Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways.},
journal = {Cell death & disease},
volume = {15},
number = {9},
pages = {707},
pmid = {39349423},
issn = {2041-4889},
support = {2021R1A2B5B01001482//National Research Foundation of Korea (NRF)/ ; 2021R1A2C4002003//National Research Foundation of Korea (NRF)/ ; },
mesh = {Animals ; *Mitochondrial Dynamics/drug effects ; *Oxidative Stress/drug effects ; *Dynamins/metabolism/genetics ; *Glutathione Peroxidase GPX1 ; *NF-kappa B/metabolism ; *Signal Transduction ; *Parvalbumins/metabolism ; *Cyclin-Dependent Kinase 5/metabolism/genetics ; *Glutathione Peroxidase/metabolism/genetics ; *Down-Regulation/drug effects ; Neurons/metabolism/drug effects ; Male ; Mice ; Quinazolinones/pharmacology ; Phosphorylation/drug effects ; Buthionine Sulfoximine/pharmacology ; Mitochondria/metabolism/drug effects ; },
abstract = {Loss of parvalbumin (PV) expressing neurons (PV neurons) is relevant to the underlying mechanisms of the pathogenesis of neurological and psychiatric diseases associated with the dysregulation of neuronal excitatory networks and brain metabolism. Although PV modulates mitochondrial morphology, volume and dynamics, it is largely unknown whether mitochondrial dynamics affect PV expression and what the molecular events are responsible for PV neuronal degeneration. In the present study, L-buthionine sulfoximine (BSO, an inhibitor of glutathione synthesis) did not degenerate PV neurons under physiological condition. However, BSO-induced oxidative stress decreased PV expression and facilitated cyclin-dependent kinase 5 (CDK5) tyrosine (Y) 15 phosphorylation, dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and glutathione peroxidase-1 (GPx1) downregulation in PV neurons. Co-treatment of roscovitine (a CDK5 inhibitor) or mitochondrial division inhibitor-1 (Mdivi-1, an inhibitor of mitochondrial fission) attenuated BSO-induced PV downregulation. WY14643 (an inducer of mitochondrial fission) reduced PV expression without affecting CDK5 Y15 phosphorylation. Following status epilepticus (SE), CDK5 Y15 phosphorylation and mitochondrial fission were augmented in PV neurons. These were accompanied by reduced GPx1-mediated inhibition of NF-κB p65 serine (S) 536 phosphorylation. N-acetylcysteine (NAC), roscovitine and Mdivi-1 ameliorated SE-induced PV neuronal degeneration by mitigating CDK5 Y15 hyperphosphorylation, aberrant mitochondrial fragmentation and reduced GPx1-mediated NF-κB inhibition. Furthermore, SN50 (a NF-κB inhibitor) alleviated SE-induced PV neuronal degeneration, independent of dysregulation of mitochondrial fission, CDK5 hyperactivation and GPx1 downregulation. These findings provide an evidence that oxidative stress may activate CDK5-DRP1- and GPx1-NF-κB-mediated signaling pathways, which would be possible therapeutic targets for preservation of PV neurons in various diseases.},
}

Animals
*Mitochondrial Dynamics/drug effects
*Oxidative Stress/drug effects
*Dynamins/metabolism/genetics
*Glutathione Peroxidase GPX1
*NF-kappa B/metabolism
*Signal Transduction
*Parvalbumins/metabolism
*Cyclin-Dependent Kinase 5/metabolism/genetics
*Glutathione Peroxidase/metabolism/genetics
*Down-Regulation/drug effects
Neurons/metabolism/drug effects
Male
Mice
Quinazolinones/pharmacology
Phosphorylation/drug effects
Buthionine Sulfoximine/pharmacology
Mitochondria/metabolism/drug effects

@article {pmid39351494,
year = {2024},
author = {Li, P and Zhou, H and Yang, Y and Wu, M and Zhao, D and Wang, L and Yi, D and Hou, Y},
title = {Dietary supplementation with N-acetylcysteine confers a protective effect on muscle and liver in lipopolysaccharide-challenged piglets.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1458912},
pmid = {39351494},
issn = {2296-861X},
abstract = {N-acetylcysteine (NAC) is a well-established antioxidant that offers exciting opportunities for intestinal health in weaned piglets, while the effects of NAC on muscle and liver has not been fully characterized. Therefore, the present study was performed to investigate the effects of dietary supplementation with NAC on muscle and liver in weaned piglets challenged with lipopolysaccharide (LPS). Twenty-four piglets (24-day-old) were randomly assigned to three treatment groups, the piglets in the control (CTR) and LPS- challenged (LPS) groups were fed the basal diet and those in the LPS+ NAC group was fed the basal diet supplemented with 500 mg/kg NAC. The animal trial lasted for 21 days. At the end of the trial, piglets in the LPS and LPS+ NAC groups were injected intraperitoneally with LPS (100 μg/kg body weight) and piglets in the CTR group were administrated with an equal volume of normal saline. 3 h later, the blood was collected and tissue samples were obtained after 6 h of LPS or normal saline treatment. The results showed that the level of IL-1β, and the mRNA levels of C-X-C motif chemokine receptor 3 (CXCR3) and interferon-γ (IFN-γ) in the liver were up-regulated, and the mRNA levels of insulin-like growth factor 1 (IGF-1), total glutathione (T-GSH), and the ratio of total protein to DNA in the liver were decreased under LPS challenge (P < 0.05). At the same time, LPS increased the level of H2O2 and decreased the content of T-GSH and DNA in the longissimus dorsi and gastrocnemius muscles (P < 0.05). In addition, the percentage of monocytes and the level of epidermal growth factor (EGF) were down-regulated in the LPS treatment (P < 0.05). Interestingly, dietary NAC supplementation reversed the above changes induced by LPS (P < 0.05). Furthermore, NAC might alleviate the muscle and liver injury in LPS-challenged piglets by regulating the expression of genes related to the type I interferon signaling pathway, as well as hypoxia inducible factor 1 (HIF1) and nuclear factor erythroid-2 related factor 2 (Nrf-2). Our findings suggested that dietary supplementation with NAC could benefit the health of muscle and liver in LPS-challenged weaned piglets.},
}

@article {pmid39353794,
year = {2024},
author = {Rajaratnam, G and Baldwin, AJ},
title = {"To BAL or not to BAL, that is the question": Variations in smoke inhalation injury guidelines from burn units and centres in England, Scotland and Wales.},
journal = {Burns : journal of the International Society for Burn Injuries},
volume = {50},
number = {9},
pages = {107273},
doi = {10.1016/j.burns.2024.09.012},
pmid = {39353794},
issn = {1879-1409},
mesh = {Humans ; *Smoke Inhalation Injury/therapy ; Cross-Sectional Studies ; *Practice Guidelines as Topic ; Wales ; Scotland ; England ; *Burn Units ; *Bronchoscopy/methods ; Bronchoalveolar Lavage/methods ; Adult ; Carbon Monoxide Poisoning/therapy ; Carboxyhemoglobin/analysis ; Guideline Adherence/statistics & numerical data ; Acetylcysteine/therapeutic use ; },
abstract = {AIM: To evaluate variations in diagnostic criteria and management recommendations for smoke inhalation injury (SII) amongst the burn networks of England, Scotland, and Wales.

METHODS: A descriptive cross-sectional study examining SII guidelines provided by adult burn units and centres in England, Scotland and Wales.

RESULTS: All 16 adult burn units and centres responded. Fourteen (87.5 %) had guidelines. Due to sharing of guidelines, ten unique guidelines were assessed. Diagnostic criteria showed variability with no universal criterion shared amongst guidelines. Bronchoscopy was recommended by 90 % of guidelines, but the timing varied. The use of bronchoscopic scoring systems was recommended by four guidelines. Bronchoalveolar lavage (BAL) was recommended by four, with considerable variation in frequency and choice of lavage fluid. All guidelines advised at least one nebulised agent: heparin (n = 8); N-acetyl cysteine (NAC) (n = 8); or salbutamol (n = 8). All guidelines included advice on carbon monoxide poisoning; however, carboxyhaemoglobin (COHb) cut-off levels for treatment varied (5 % [n-4], 10 % [n = 3], 15 % [n = 1]). All recommended high-flow oxygen. Seven (70 %) guidelines offered guidance on cyanide poisoning. Reduced/altered consciousness was the only consistent diagnostic criterion. Five (50 %) guidelines provided intubation guidance, emphasising the role of a 'senior clinician' as the intubator. Ventilatory guidance appeared in eight guidelines, focusing on lung protective ventilation (n = 8); oxygenation goals (n = 3); and permissive hypercapnia (n = 3). Within lung-protective ventilation, advice on tidal volume (6, or 6-8 ml/kg) and plateau pressures (>30 cmH2O) were presented most commonly (n = 7).

CONCLUSION: This study has outlined the substantial variations in guidance for the management of SII. The results underscore the need for a national guideline outlining a standardised approach to the diagnosis and management of SII, within the limitations of the current evidence.},
}

Humans
*Smoke Inhalation Injury/therapy
Cross-Sectional Studies
*Practice Guidelines as Topic
Wales
Scotland
England
*Burn Units
*Bronchoscopy/methods
Bronchoalveolar Lavage/methods
Adult
Carbon Monoxide Poisoning/therapy
Carboxyhemoglobin/analysis
Guideline Adherence/statistics & numerical data
Acetylcysteine/therapeutic use

@article {pmid39357253,
year = {2025},
author = {Huang, W and He, M and Chen, S and Yin, G and Gan, Y and Li, H and Wu, C and Yin, P},
title = {Dual-Channel fluorescent detection of Biothiols: A novel probe for Distinguishing Cysteine, Homocysteine, Glutathione, and N-Acetylcysteine in cellular environments.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {326},
number = {},
pages = {125221},
doi = {10.1016/j.saa.2024.125221},
pmid = {39357253},
issn = {1873-3557},
mesh = {*Fluorescent Dyes/chemistry ; *Acetylcysteine/chemistry ; *Glutathione/analysis/blood ; *Homocysteine/analysis/blood ; Humans ; *Cysteine/analysis/blood ; *Spectrometry, Fluorescence/methods ; Sulfhydryl Compounds/analysis/chemistry/blood ; Limit of Detection ; Optical Imaging ; Coumarins/chemistry ; },
abstract = {Biothiols, including cysteine (Cys), homocysteine (Hcy), glutathione (GSH), and N-acetylcysteine (NAC), possess similar chemical structures and properties but play crucial, distinct roles in biological cells and blood serum. Imbalances in the concentrations of these biothiols are associated with various diseases, highlighting the importance of precise discrimination, especially between Cys and other biothiols. Owing to the similarity of the chemical properties of Cys, Hcy, GSH, and NAC, developing an effective methodology to differentiate these thiol compounds is challenging. In this study, we designed and synthesized a novel dual-channel fluorescent probe, hereafter referred to as CNTC, by integrating coumarin and acrylonitrile. This probe enabled the simultaneous discrimination of Cys from Hcy, GSH, and NAC, producing distinct fluorescent signals: blue for Cys and green for Hcy, GSH, and NAC. CNTC exhibited rapid response kinetics (within 30 min) and impressive detection limits of 0.31, 0.11, 0.029, and 0.032 μM for Cys, Hcy, GSH, and NAC, respectively. Furthermore, CNTC was successfully applied in the fluorescence imaging of both exogenous and endogenous Cys, Hcy, GSH, and NAC in living cells. The remarkable analytical and bioimaging capabilities of CNTCin vivo establish it as a promising tool for elucidating the pathophysiological roles of biothiols, particularly Cys, Hcy, GSH, and NAC.},
}

*Fluorescent Dyes/chemistry
*Acetylcysteine/chemistry
*Glutathione/analysis/blood
*Homocysteine/analysis/blood
Humans
*Cysteine/analysis/blood
*Spectrometry, Fluorescence/methods
Sulfhydryl Compounds/analysis/chemistry/blood
Limit of Detection
Optical Imaging
Coumarins/chemistry

@article {pmid39360158,
year = {2024},
author = {Liu, L and Pang, W and Liu, J and Xu, S and Zhang, Z and Hao, R and Wan, J and Xie, W and Tao, X and Yang, P and Zhao, L and Zhai, Z and Wang, C},
title = {Inhibition of heterogeneous nuclear ribonucleoproteins A1 and oxidative stress reduces glycolysis via pyruvate kinase M2 in chronic thromboembolic pulmonary hypertension.},
journal = {Journal of translational internal medicine},
volume = {12},
number = {4},
pages = {437-451},
pmid = {39360158},
issn = {2450-131X},
abstract = {BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a lethal complication of pulmonary embolism involving pulmonary artery occlusion and microvascular disease. The glucose metabolism and reactive oxygen species (ROS) production may be perturbed in CTEPH, but the precise mechanisms are unclear. This study investigated glucose metabolism in CTEPH employing pulmonary endarterectomy (PEA)-derived pulmonary artery smooth muscle cells (PASMCs) and characterized the roles of pyruvate kinase M2 (PKM2) and its regulation by heterogeneous nuclear ribonucleoproteins A1 (hnRNPA1) and ROS in CTEPH.

METHODS: PEA tissues and blood samples of CTEPH patients were collected to study the levels of PKM2. Primary PASMCs were isolated from PEA tissues. We used small interfering RNAs to knock down PKM2 and hnRNPAI, and applied antioxidant N-acetylcysteine (NAC) and mito-TEMPO to reduce ROS production. The expression of glucometabolic genes, ROS production, glycolysis rate and proliferative and migratory activities were analyzed in PEA-derived PASMCs.

RESULTS: PKM2 levels in serum and PEA tissues of CTEPH patients were higher than that of the healthy controls. Compared to the control PASMCs, PEA-derived PASMCs showed increased PKM2 expression and ROS production. The rates of glycolysis, proliferation and migration were increased in PEA-PASMCs and could be mitigated by PKM2 downregulation through hnRNPA1 or ROS inhibition.

CONCLUSIONS: Increased glycolysis and PKM2 expression were found in PEA-PASMCs. Inhibition of hnRNPA1 or ROS corrected the aberrant glycolysis, cell proliferation and migration by downregulating PKM2. Regulation of the hnRNPA1/PKM2 axis represents a potential therapeutic target for the treatment of CTEPH.},
}

@article {pmid39360368,
year = {2024},
author = {D'Agostino Gennari, J and Deveza, GBH and Ribeiro, CT and Seguro, AC and Aikawa, NE and Shimizu, MHM and Leon, EP and Guedes, LKN and Kupa, LVK and Silva, CAA and Bonfa, E and Pasoto, SG},
title = {Efficacy of N-acetylcysteine for treating dryness symptoms of Sjögren's disease: randomised placebo-controlled double-blind clinical study.},
journal = {Clinical and experimental rheumatology},
volume = {42},
number = {12},
pages = {2427-2436},
doi = {10.55563/clinexprheumatol/dmd5dv},
pmid = {39360368},
issn = {0392-856X},
mesh = {Humans ; *Acetylcysteine/therapeutic use/administration & dosage ; *Sjogren's Syndrome/drug therapy/complications/diagnosis/blood ; Double-Blind Method ; Female ; Middle Aged ; Adult ; Treatment Outcome ; *Xerostomia/drug therapy/etiology ; Glutathione/blood ; Thiobarbituric Acid Reactive Substances/metabolism ; Aged ; Biomarkers/blood ; Time Factors ; },
abstract = {OBJECTIVES: N-acetylcysteine (NAC) is used in Sjögren's disease (SjD) based on limited evidence. The aim of this study was to assess the efficacy of NAC for relieving dryness symptoms in SjD.

METHODS: In this placebo-controlled double-blind trial, 60 adult SjD females (with low disease activity) were randomised to receive NAC (1,200 mg/day orally) or placebo. At baseline (D0), 30 days (D30) and 90 days (D90), all participants underwent the following evaluations: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Ocular Surface Disease Index (OSDI), Xerostomia Inventory (XI), Leicester Cough Questionnaire (LCQ), unstimulated/stimulated salivary flow, Schirmer's test, and plasma levels of thiobarbituric acid reactive substances (TBARS), glutathione and NAC.

RESULTS: At inclusion, both groups were balanced for age, ethnicity, disease duration, ESSPRI, OSDI, XI, Schirmer's test, salivary flow, ESSDAI and topical/systemic treatments (p>0.05). No significant differences were observed between NAC and placebo groups on D30 and D90 regarding ESSPRI, XI, OSDI, LCQ, Schirmer's test, stimulated salivary flow, ESSDAI and topical/systemic treatments (p>0.05). Unstimulated salivary flow was significantly higher in the placebo group on D90 (p=0.018). NAC blood concentrations were significantly higher in the NAC group on D30 (p=0.018) and D90 (p<0.001), however, no differences were found in TBARS and glutathione. Further analysis showed decrease≥1 in ESSPRI in the NAC compared with placebo group on D30 (p=0.045), a result not found on D90 (p=0.696).

CONCLUSIONS: NAC is recommended as a rescue therapy for SjD. However, our well-designed study provides novel evidence demonstrating its inefficacy for improving dryness symptoms or reducing oxidative stress.

CLINICALTRIALS: gov-NCT04793646.},
}

Humans
*Acetylcysteine/therapeutic use/administration & dosage
*Sjogren's Syndrome/drug therapy/complications/diagnosis/blood
Double-Blind Method
Female
Middle Aged
Adult
Treatment Outcome
*Xerostomia/drug therapy/etiology
Glutathione/blood
Thiobarbituric Acid Reactive Substances/metabolism
Aged
Biomarkers/blood
Time Factors

@article {pmid39363690,
year = {2024},
author = {Li, K and Jiang, L and Wei, Y and Li, Z},
title = {Identification of the metabolites of nimbolide in rat by liquid chromatography combined with quadrupole/orbitrap mass spectrometry.},
journal = {Biomedical chromatography : BMC},
volume = {38},
number = {12},
pages = {e6012},
doi = {10.1002/bmc.6012},
pmid = {39363690},
issn = {1099-0801},
mesh = {Animals ; Rats ; Male ; *Microsomes, Liver/metabolism ; *Rats, Sprague-Dawley ; *Limonins/metabolism/pharmacokinetics/chemistry/urine/analysis ; Chromatography, High Pressure Liquid/methods ; Tandem Mass Spectrometry/methods ; Bile/chemistry/metabolism ; },
abstract = {Nimbolide is a major furanoid compound isolated from Azadirachta indica. The aim of this study was to characterize the metabolites of nimbolide in rats and to propose the metabolic pathways. The metabolites were generated by incubating nimbolide (10 μM) with rat liver microsomes, nicotinamide adenine dinucleotide phosphate (NADPH), and nucleophiles (glutathione [GSH] or N-acetyl-lysine [NAL]) at 37°C for 60 min. For the in vivo study, nimbolide was intravenously administered to rats at a single dose of 10 mg/kg, and the bile and urine were collected. The metabolites were identified by ultra-high-performance liquid chromatography-quadrupole/orbitrap mass spectrometry (UPLC-Q/Orbitrap-MS) using electrospray ionization in positive ion mode. Totally, nine metabolites were detected, and their identities were characterized by accurate MS and MS/MS data. In GSH-supplemented liver microsomes, GSH conjugation was the primary elimination pathway. The furan ring was bioactivated into cis-butene-1,4-dial that can be trapped by GSH. In NAL-supplemented liver microsomes, two NAL conjugates (M4 and M5) derived from cis-butene-1,4-dial were observed. In rat bile and urine, N-acetyl-cysteine, cysteine-glycine, and GSH conjugate were also found. The current study provides an overview of the metabolism and the bioactivation profiles of nimbolide in rats, which aids in understanding its safety and activity.},
}

Animals
Rats
Male
*Microsomes, Liver/metabolism
*Rats, Sprague-Dawley
*Limonins/metabolism/pharmacokinetics/chemistry/urine/analysis
Chromatography, High Pressure Liquid/methods
Tandem Mass Spectrometry/methods
Bile/chemistry/metabolism

@article {pmid39365126,
year = {2024},
author = {Kapoor, MC},
title = {N-acetyl Cysteine to Mitigate Liver Damage in Patients with Deranged Liver Function Undergoing Surgery on Cardiopulmonary Bypass.},
journal = {Annals of cardiac anaesthesia},
volume = {27},
number = {4},
pages = {299-300},
pmid = {39365126},
issn = {0974-5181},
mesh = {Female ; Humans ; Male ; *Acetylcysteine/therapeutic use ; *Cardiopulmonary Bypass/adverse effects ; Liver/drug effects ; Liver Diseases ; Liver Function Tests ; },
}

Female
Humans
Male
*Acetylcysteine/therapeutic use
*Cardiopulmonary Bypass/adverse effects
Liver/drug effects
Liver Diseases
Liver Function Tests

@article {pmid39365130,
year = {2024},
author = {Ram Kiran, KS and Trivedi, V and Rajesh, VSP and Sharma, M and Haranal, M and Pandya, H},
title = {Role of Prophylactic N-Acetylcysteine Supplementation on Postoperative Outcomes in Patients Undergoing Elective Double-Valve Replacement (Aortic and Mitral Valve).},
journal = {Annals of cardiac anaesthesia},
volume = {27},
number = {4},
pages = {324-329},
pmid = {39365130},
issn = {0974-5181},
mesh = {Humans ; *Acetylcysteine/therapeutic use ; Double-Blind Method ; Female ; Male ; Prospective Studies ; *Postoperative Complications/prevention & control/epidemiology ; *Heart Valve Prosthesis Implantation/methods ; Middle Aged ; *Mitral Valve/surgery ; *Aortic Valve/surgery ; Treatment Outcome ; Adult ; Free Radical Scavengers/therapeutic use ; Length of Stay/statistics & numerical data ; Liver Function Tests ; Aged ; Elective Surgical Procedures ; Liver Diseases/prevention & control ; },
abstract = {AIMS AND OBJECTIVES: The incidence of postoperative liver dysfunction is high in patients undergoing double-valve replacement - mitral and aortic valve replacement (DVR). This study aims to evaluate N-acetylcysteine's free radical scavenging property (NAC) to prevent postoperative liver dysfunction in these patients, thus affecting overall clinical outcomes.

METHODS: A single-center, prospective, randomized, double-blinded interventional study of 60 patients divided into two groups of 30 each. Group N received prophylactic intravenous NAC, and Group C received volume-matched 5% dextrose. Data comprised demographics, liver function tests (LFT), renal function tests (RFT), vasoactive-inotropic scores (VIS) score, and C-reactive protein (CRP) at various time intervals. Postoperative parameters such as ventilation duration, length of stay in ICU (LOS-ICU), length of hospital stay (LOHS), atrial fibrillation (AF), acute kidney injury (AKI) requiring hemodialysis, and mortality were noted. Statistical analysis was performed with the Student's t-test and Chi-square test (SPSS 22 software).

RESULTS: All postoperative LFT parameters (total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase (ALP)) were significantly lower (P < 0.05) at 24, 48, and 72 hours in Group N compared to Group C. RFT and VIS scores were lower in Group N; however, were not statistically significant except for Serum Creatinine at 48 hours (P = 0.0478). Ventilation duration (P = 0.0465) and LOS-ICU (P = 0.0431) were significantly lower in Group N. Other outcomes like AF, LOHS, and mortality were lower in Group N but were not statistically significant.

CONCLUSION: Our study showed that prophylactic administration of NAC in patients undergoing DVR is associated with a reduction in the incidence of postoperative liver dysfunction with a positive impact on postoperative outcomes.},
}

Humans
*Acetylcysteine/therapeutic use
Double-Blind Method
Female
Male
Prospective Studies
*Postoperative Complications/prevention & control/epidemiology
*Heart Valve Prosthesis Implantation/methods
Middle Aged
*Mitral Valve/surgery
*Aortic Valve/surgery
Treatment Outcome
Adult
Free Radical Scavengers/therapeutic use
Length of Stay/statistics & numerical data
Liver Function Tests
Aged
Elective Surgical Procedures
Liver Diseases/prevention & control

@article {pmid39366552,
year = {2024},
author = {Ishtiaq, A and Mushtaq, I and Rehman, H and Mushtaq, I and Mushtaq, I and Abbasi, SW and Liaqat, F and Rasheed, A and Ahmad, S and Akhtar, Z and Murtaza, I},
title = {Tetra aniline-based polymers ameliorate BPA-induced cardiotoxicity in Sprague Dawley rats, in silico and in vivo analysis.},
journal = {Life sciences},
volume = {358},
number = {},
pages = {123104},
doi = {10.1016/j.lfs.2024.123104},
pmid = {39366552},
issn = {1879-0631},
mesh = {Animals ; *Phenols/pharmacology/toxicity ; *Rats, Sprague-Dawley ; *Benzhydryl Compounds/toxicity ; Rats ; *Cardiotoxicity/metabolism/prevention & control ; *Aniline Compounds/pharmacology/toxicity ; *Molecular Docking Simulation ; Reactive Oxygen Species/metabolism ; Oxidative Stress/drug effects ; Polymers ; Male ; MicroRNAs/metabolism/genetics ; Antioxidants/pharmacology ; Computer Simulation ; Apoptosis/drug effects ; Bisphenol A Compounds ; },
abstract = {AIMS: Bisphenol A (BPA), xenoestrogen, is an environmental toxicant, that generates oxidative stress leading to cardiotoxicity. The oxidative stress can be neutralized by natural and synthetic antioxidants. The present study elucidates the highly selective antioxidative potential of synthetic tetra aniline polymers Es-37 and L-37 against Bisphenol A-induced cardiac cellular impairments and the role of miRNA-15a-5p in the regulation of different apoptotic proteins.

MATERIALS AND METHODS: The molecular docking of L-37 and Es-37 with three proteins (p53, Cytochrome c, and Bcl-2) were performed. The dose of 1 mg/kg BW of BPA, 1 mg/kg BW Es-37 and L-37 and 50 mg/kg BW N-acetyl cysteine (NAC) was administered to Sprague Dawley rats. The miRNA and target gene expression were confirmed by qRt-PCR and Immunoblotting.

KEY FINDINGS: In our results, BPA administration significantly elevated the reactive oxygen species (ROS), p53, cytochrome c, and particularly miRNA-15a-5p expression; however: these changes were notably reversed by Es-37 and L-37 treatment. Additionally, molecular docking of synthetic polymers validated that L-37 has a greater binding affinity with the target proteins compared to Es-37, with the highest binding values reported for the enzymatic protein cytochrome c.

SIGNIFICANCE: These results suggest that both synthetic polymers Es-37 and L-37 have the potential to scavenge free radicals, boost-up antioxidant enzyme activities, and avert (BPA-induced) toxicity, thus, may serve as cardioprotective agents. Moreover, this study first time proposes that miRNA-15a-5p overexpression is associated with oxidative stress and coincides with BPA induced cardiotoxicity, thus may serve as potential therapeutic target in future.},
}

Animals
*Phenols/pharmacology/toxicity
*Rats, Sprague-Dawley
*Benzhydryl Compounds/toxicity
Rats
*Cardiotoxicity/metabolism/prevention & control
*Aniline Compounds/pharmacology/toxicity
*Molecular Docking Simulation
Reactive Oxygen Species/metabolism
Oxidative Stress/drug effects
Polymers
Male
MicroRNAs/metabolism/genetics
Antioxidants/pharmacology
Computer Simulation
Apoptosis/drug effects
Bisphenol A Compounds

@article {pmid39371865,
year = {2024},
author = {Gupta, M and Sharma, A and Kumaran, MS},
title = {An Insight Into Adolescent Dermatitis Artefacta: A Case Report.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e68682},
pmid = {39371865},
issn = {2168-8184},
abstract = {Dermatitis artefacta (DA) is a rare and challenging-to-diagnose factitious dermatological disorder, most commonly affecting late adolescents and young adults. This case report presents a 17-year-old girl with a history of unexplained linear lesions on her face and abdomen persisting for 11 months, leading to significant school absenteeism. The dermatological examination was otherwise unremarkable except for multiple well-defined excoriations, erosions, and scarring, suggestive of DA. Dermoscopic examination supported this diagnosis, showing characteristic features. The patient was treated with N-acetyl cysteine and referred for psychiatric evaluation, highlighting the intricate nature of managing DA, particularly in young individuals who may have underlying psychological distress. The case underscores the importance of a multidisciplinary approach in diagnosing and treating DA, given its overlap with other neuropsychiatric and dermatological disorders.},
}

@article {pmid39376972,
year = {2024},
author = {Eghdami, S and Eissazade, N and Heidari Mokarar, M and Boroon, M and Orsolini, L and Shalbafan, M},
title = {The safety and efficacy of N-acetylcysteine as an augmentation in the treatment of obsessive-compulsive disorder in adults: a systematic review and meta-analysis of randomized clinical trials.},
journal = {Frontiers in psychiatry},
volume = {15},
number = {},
pages = {1421150},
pmid = {39376972},
issn = {1664-0640},
abstract = {BACKGROUND: Obsessive-compulsive disorder (OCD) ranks as the fourth most prevalent psychiatric disorder, with selective serotonin reuptake inhibitors (SSRIs) as its mainstay pharmacological treatment. However, approximately 40 to 60% of patients do not adequately respond to initial treatment, highlighting the need for alternative options. N-acetylcysteine (NAC) is one of the several medications that have been used in augmentation with SSRIs to enhance their efficacy.

OBJECTIVES: We aimed to investigate the safety and efficacy of NAC, a glutamate-modulating agent, as an augmentation in the treatment of moderate to severe OCD.

METHOD: We conducted a thorough search across PubMed, Scopus, Web of science, and ProQuest to identify relevant trials published until December 2023. The primary outcome of interest was the mean difference between the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores before and after administrating augmented NAC among patients with moderate to severe OCD. Furthermore, we compared the occurrence of adverse drug events between the experimental and control groups.

RESULTS: We included six randomized controlled trials with 195 patients. The results of our study indicated a positive outcome for the experimental group in terms of the total Y-BOCS score when using the medication for a period of five to eight weeks (p-Value = 0.05). However, no significant difference was observed for durations shorter than five weeks or longer than 12 weeks. Additionally, no significant difference was found between the two groups in terms of the obsession and compulsion Y-BOCS scores. Furthermore, no significant differences were observed in terms of adverse events.

CONCLUSION: Augmentation of NAC with SSRIs may benefit patients with moderate to severe OCD. However, it is necessary to conduct additional multi-center trials over extended periods to develop a comprehensive strategy for action.

https://www.crd.york.ac.uk/prospero/, identifier CRD42023463683.},
}

@article {pmid39377544,
year = {2024},
author = {Formato, A and Salbini, M and Orecchini, E and Pellegrini, M and Buccarelli, M and Vitiani, LR and Giannetti, S and Pallini, R and D'Alessandris, QG and Lauretti, L and Martini, M and De Falco, V and Levi, A and Falchetti, ML and Mongiardi, MP},
title = {N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.},
journal = {Cancer medicine},
volume = {13},
number = {19},
pages = {e70279},
pmid = {39377544},
issn = {2045-7634},
support = {A0375-2020-36524//Gruppi di Ricerca 2020-POR-FESR Lazio 2014-2020/ ; IG 2021#25664//Associazione Italiana per la Ricerca sul Cancro/ ; RF-2019-12368786//Ministero della Salute/ ; },
mesh = {*Axitinib/pharmacology/therapeutic use ; Animals ; *Glioblastoma/drug therapy/pathology/metabolism ; Humans ; Mice ; *Acetylcysteine/pharmacology/therapeutic use ; *Xenograft Model Antitumor Assays ; *Brain Neoplasms/drug therapy/pathology/metabolism ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Protein Kinase Inhibitors/pharmacology/adverse effects/therapeutic use ; Cellular Senescence/drug effects ; },
abstract = {OBJECTIVE: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH-wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo-angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib-dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells.

METHODS: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N-Acetyl-L-Cysteine (NAC) might be used to reduce senescence-associated adverse effects of axitinib treatment without altering its anti-tumor activity.

RESULTS: We demonstrate that the use of the antioxidant molecule N-Acetyl-Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib-dependent toxicity.

CONCLUSION: Overall, we found that NAC co-treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib-dependent toxicity.},
}

*Axitinib/pharmacology/therapeutic use
Animals
*Glioblastoma/drug therapy/pathology/metabolism
Humans
Mice
*Acetylcysteine/pharmacology/therapeutic use
*Xenograft Model Antitumor Assays
*Brain Neoplasms/drug therapy/pathology/metabolism
Reactive Oxygen Species/metabolism
Cell Line, Tumor
Disease Models, Animal
Protein Kinase Inhibitors/pharmacology/adverse effects/therapeutic use
Cellular Senescence/drug effects

@article {pmid39381531,
year = {2024},
author = {Ghazaiean, M and Aliasgharian, A and Karami, H and Ghasemi, MM and Darvishi-Khezri, H},
title = {Antioxidative effects of N-acetylcysteine in patients with β-thalassemia: A quick review on clinical trials.},
journal = {Health science reports},
volume = {7},
number = {10},
pages = {e70096},
pmid = {39381531},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Several studies have highlighted the potent antioxidant properties of N-acetyl cysteine (NAC). This review aimed to assess the impact of NAC on oxidative stress biomarkers in patients with β-thalassemia.

METHODS: The review included articles published before 2024 that investigated the effects of NAC on oxidative stress in individuals with β-thalassemia. A comprehensive search was conducted across various databases, including Scopus, PubMed, Web of Science, Trip, and CENTRAL. Only English-language clinical trials were considered for inclusion in this review. Besides, the number needed to treat (NNT) was calculated based on the included studies.

RESULTS: Ninety-nine articles were retrieved from electronic databases, and after a thorough review, eight articles were selected for comprehensive text analysis. The highest dose of NAC administered was 10 mg/kg/day (equivalent to 600 mg/day) over a period of 3-6 months. All the studies assessing the impact of NAC on oxidative stress indicators in β-thalassemia patients demonstrated positive effects during the 3-month follow-up period. Most estimated NNTs fell into 1-5, suggesting significant clinical therapeutic value in this context.

CONCLUSION: The current potency of NAC alone appears to be effective in ameliorating oxidative stress in patients with β-thalassemia major. While a 3-month duration seems adequate to demonstrate the antioxidant properties of NAC in this population, larger and well-designed clinical trials are warranted. Current clinical evidence possesses a high risk of bias.},
}

@article {pmid39384146,
year = {2024},
author = {Zeng, Q and Lv, C and Qi, L and Wang, Y and Hao, S and Li, G and Sun, H and Du, L and Li, J and Wang, C and Zhang, Y and Wang, X and Ma, R and Wang, T and Li, Q},
title = {Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming.},
journal = {Life sciences},
volume = {357},
number = {},
pages = {123109},
doi = {10.1016/j.lfs.2024.123109},
pmid = {39384146},
issn = {1879-0631},
mesh = {Humans ; Animals ; *Reactive Oxygen Species/metabolism ; *Uterine Cervical Neoplasms/drug therapy/pathology/metabolism ; Female ; Mice ; *Mice, Nude ; *Glucose/metabolism ; *Apoptosis/drug effects ; *Cell Proliferation/drug effects ; *Sodium Selenite/pharmacology ; *Xenograft Model Antitumor Assays ; HeLa Cells ; Glycolysis/drug effects ; Mice, Inbred BALB C ; Membrane Potential, Mitochondrial/drug effects ; Cell Line, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Disease Progression ; Metabolic Reprogramming ; },
abstract = {AIMS: This study aims to explore the inhibitory effect of selenium on cervical cancer through suppression of glucose metabolic reprogramming and its underlying mechanisms.

METHODS: Sodium selenite (SS) treated HeLa and SiHa cells were assessed for proliferation using the CCK-8 assay and immunofluorescence. DNA synthesis was measured with the EdU assay. A nude mouse xenograft model evaluated SS's anti-cervical cancer effects. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured using flow cytometry, DCFH-DA, and JC-1 probes, respectively. Apoptosis was detected via Annexin V/PI staining and Western blot. Glucose uptake, lactate production, and ATP generation were determined using 2-NBDG probes and assay kits. The mRNA and protein levels of glycolysis-related genes HK2, GLUT1, and PDK1 were measured using RT-qPCR and Western blot.

KEY FINDINGS: SS inhibited HeLa and SiHa cells viability in a dose- and time-dependent manner. Intraperitoneal injection of SS in nude mice significantly inhibited HeLa cell xenograft growth without evident hepatotoxicity or nephrotoxicity. SS inhibited glucose metabolic reprogramming in cancer cells primarily via ROS-mediated AKT/mTOR/HIF-1α pathway inhibition. Pretreatment with N-acetylcysteine (NAC) or MHY1485 (an mTOR activator) partially reversed the inhibitory effects of SS on glucose metabolic reprogramming, cell proliferation, and migration, as well as its pro-apoptotic effects.

SIGNIFICANCE: SS exhibited anti-cervical cancer effects, likely through the induction of ROS generation and inhibition of glucose metabolic reprogramming in cervical cancer cells, thereby inhibiting cell proliferation and promoting apoptosis. These findings provide new insights into understanding the molecular mechanisms underlying SS for potential new drug development for cervical cancer.},
}

Humans
Animals
*Reactive Oxygen Species/metabolism
*Uterine Cervical Neoplasms/drug therapy/pathology/metabolism
Female
Mice
*Mice, Nude
*Glucose/metabolism
*Apoptosis/drug effects
*Cell Proliferation/drug effects
*Sodium Selenite/pharmacology
*Xenograft Model Antitumor Assays
HeLa Cells
Glycolysis/drug effects
Mice, Inbred BALB C
Membrane Potential, Mitochondrial/drug effects
Cell Line, Tumor
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
Disease Progression
Metabolic Reprogramming

@article {pmid39389326,
year = {2025},
author = {Qiao, J and Du, D and Wang, Y and Xi, L and Zhu, W and Morigen, },
title = {Uncovering the effects of non-lethal oxidative stress on replication initiation in Escherichia coli.},
journal = {Gene},
volume = {933},
number = {},
pages = {148992},
doi = {10.1016/j.gene.2024.148992},
pmid = {39389326},
issn = {1879-0038},
mesh = {*Oxidative Stress/drug effects ; *Escherichia coli/genetics/metabolism/drug effects ; *Escherichia coli Proteins/genetics/metabolism ; *DNA Replication/drug effects ; *Hydrogen Peroxide/pharmacology ; Superoxide Dismutase/metabolism/genetics ; Protease La/metabolism/genetics ; Bacterial Proteins/genetics/metabolism ; DNA Glycosylases/genetics/metabolism ; Endopeptidase Clp/genetics/metabolism ; Acetylcysteine/pharmacology ; Catalase ; },
abstract = {Cell cycle adaptability assists bacteria in response to adverse stress. The effect of oxidative stress on replication initiation in Escherichia coli remains unclear. This work examined the impact of exogenous oxidant and genetic mutation-mediated oxidative stress on replication initiation. We found that 0-0.5 mM H2O2 suppresses E. coli replication initiation in a concentration-dependent manner but does not lead to cell death. Deletion of antioxidant enzymes SodA-SodB, KatE, or AhpC results in delayed replication initiation. The antioxidant N-acetylcysteine (NAC) promotes replication initiation in ΔkatE and ΔsodAΔsodB mutants. We then explored the factors that mediate the inhibition of replication initiation by oxidative stress. MutY, a base excision repair DNA glycosylase, resists inhibition of replication initiation by H2O2. Lon protease deficiency eliminates inhibition of replication initiation mediated by exogenous H2O2 exposure but not by katE or sodA-sodB deletion. The absence of clpP and hslV further delays replication initiation in the ΔktaE mutant, whereas hflK deletion promotes replication initiation in the ΔkatE and ΔsodAΔsodB mutants. In conclusion, non-lethal oxidative stress inhibits replication initiation, and AAA+ proteases are involved and show flexible regulation in E. coli.},
}

*Oxidative Stress/drug effects
*Escherichia coli/genetics/metabolism/drug effects
*Escherichia coli Proteins/genetics/metabolism
*DNA Replication/drug effects
*Hydrogen Peroxide/pharmacology
Superoxide Dismutase/metabolism/genetics
Protease La/metabolism/genetics
Bacterial Proteins/genetics/metabolism
DNA Glycosylases/genetics/metabolism
Endopeptidase Clp/genetics/metabolism
Acetylcysteine/pharmacology
Catalase

@article {pmid39393575,
year = {2024},
author = {Feng, J and Liu, H and Jiang, K and Gong, X and Huang, R and Zhou, C and Mao, J and Chen, Y and Xu, H and Zhang, X and Yang, X and Zhao, D},
title = {Enhanced oxidative stress aggravates BLM-induced pulmonary fibrosis by promoting cellular senescence through enhancing NLRP3 activation.},
journal = {Life sciences},
volume = {358},
number = {},
pages = {123128},
doi = {10.1016/j.lfs.2024.123128},
pmid = {39393575},
issn = {1879-0631},
mesh = {Animals ; *Bleomycin/toxicity ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Cellular Senescence/drug effects ; Mice ; *Oxidative Stress/drug effects ; *Reactive Oxygen Species/metabolism ; *Mice, Inbred C57BL ; Humans ; *Pulmonary Fibrosis/metabolism/chemically induced/pathology ; A549 Cells ; Male ; Inflammasomes/metabolism ; Disease Models, Animal ; Idiopathic Pulmonary Fibrosis/metabolism/pathology/chemically induced ; Transforming Growth Factor beta/metabolism ; },
abstract = {AIMS: Idiopathic pulmonary fibrosis (IPF) is a disease associated with aging, where increased oxidative stress accelerates the progression of pulmonary fibrosis (PF). The specific mechanisms through which oxidative stress intensifies PF are still not fully understood.

MATERIALS AND METHODS: In this study, we used bleomycin (BLM)-induced PF mouse model and TGF-β-induced collagen deposition cells for in vivo and in vitro experiments, respectively. Additionally, we employed BSO, a glutathione synthesis inhibitor, to induce excess reactive oxygen species (ROS).

KEY FINDINGS: Our findings revealed that heightened ROS production significantly exacerbated PF development in mice and increased collagen deposition in A549 cells. We also showed that cellular senescence was further intensified by the combined treatment of BSO with BLM or TGF-β, as indicated by the increased levels of p53 and p21, along with an increase in β-galactosidase-positive cells. Moreover, inflammatory responses, including inflammatory cells, inflammatory cytokines, and ROS levels were dramatically increased with the BSO and BLM or TGF-β combination. Mechanistically, we found that NLRP3 inflammasome was activated more significantly by the combined treatments of BSO with BLM or TGF-β. Inhibition of NLRP3 ameliorated the aging-related phenotype and reduced p53 and p21 expression. Furthermore, we showed that N-acetylcysteine (NAC) treatment significantly attenuated BLM or BLM plus BSO-enhanced PF in vivo.

SIGNIFICANCE: Our study demonstrates that elevated ROS levels contribute to the development of PF via NLRP3-mediated cellular senescence. We also provide that targeting oxidative stress might be an effective strategy for treating PF.},
}

Animals
*Bleomycin/toxicity
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Cellular Senescence/drug effects
Mice
*Oxidative Stress/drug effects
*Reactive Oxygen Species/metabolism
*Mice, Inbred C57BL
Humans
*Pulmonary Fibrosis/metabolism/chemically induced/pathology
A549 Cells
Male
Inflammasomes/metabolism
Disease Models, Animal
Idiopathic Pulmonary Fibrosis/metabolism/pathology/chemically induced
Transforming Growth Factor beta/metabolism

@article {pmid39394703,
year = {2024},
author = {Meng, T and Guo, HJ and Yao, Y and Mi, ZH and Tian, Y and Yu, JZ},
title = {[Study on the molecular mechanism of autophagy and apoptosis induced by ultrafine carbon black in human bronchial epithelial cells and the intervention effect of N-acetylcysteine].},
journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases},
volume = {42},
number = {9},
pages = {656-667},
doi = {10.3760/cma.j.cn121094-20231010-00080},
pmid = {39394703},
issn = {1001-9391},
support = {81502845//National Natural Science Foundation for Young Scholars of China/ ; 2021XM17//Four "Batches" Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province/ ; 202103021224311//Fundamental Research Program of Shanxi Province/ ; 20220808, XDC2021135//Innovation and Entrepreneurship Training Program for College Students/ ; },
mesh = {Humans ; *Acetylcysteine/pharmacology ; *Apoptosis/drug effects ; *Autophagy/drug effects ; *Epithelial Cells/drug effects/metabolism ; *Bronchi/cytology ; *Soot/toxicity ; *Oxidative Stress/drug effects ; Cell Line ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/metabolism ; Caspase 3/metabolism ; Caspase 9/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Malondialdehyde/metabolism ; Catalase/metabolism ; bcl-2-Associated X Protein/metabolism/genetics ; Glutathione Peroxidase/metabolism ; Cell Survival/drug effects ; },
abstract = {Objective: To investigate the molecular mechanism of autophagy and apoptosis induced by ultrafine carbon black in human bronchial epithelial cells (BEAS-2B cells), and to study the intervention effect and mechanism of N-acetylcysteine (NAC) on ultrafine carbon black-induced oxidative damage in BEAS-2B cells. Methods: In March 2023, BEAS-2B cells were used as research object, an in vitro airway model exposed to ultrafine carbon black was constructed. A control group and three carbon black exposure groups (50, 100, 200 μg/ml) were set up, and the cells were treated with corresponding concentrations of ultrafine carbon black for 24 hours. In addition, the experiment was divided into control group, NAC+ control group, 100 μg/ml carbon black exposure group and NAC+ exposure group. The corresponding groups were treated with 2 mmol/L NAC for 1 h and 100 μg/ml ultrafine carbon black for 24 h, respectively. Cell viability was measured by CCK-8 assay. Intracellular reactive oxygen species (ROS) level was detected by chemical fluorescence method. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected by colorimetry. The mRNA and protein expressions of autophagy-related genes[Atg5, Atg7, Beclin1, microtubule-associated protein light chain 3B (LC3B), p62 and lysosome-associated membrane protein 2 (LAMP2) ] and apoptosis-related genes [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and poly (ADP-ribose) polymerase 1 (PARP1) ] were determined by fluorescence quantitative PCR and Western blot. Cell apoptosis was determined by flow cytometry. Results: Compared with the control group, the relative survival rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly decreased, the levels of ROS and MDA were significantly increased, and the activities of SOD, GSH-Px and CAT were significantly decreased (P<0.05). The relative survival rate, ROS and MDA levels, SOD, GSH-Px and CAT activities were significantly correlated with the exposure dose of ultrafine carbon black (r(s)=-0.755, 0.826, 0.934, -0.810, -0.880, -0.840, P<0.05). Compared with the control group, the relative expression levels of Atg5, Atg7, Beclin1, LC3B, p62, LAMP2, Bax, Caspase3, Caspase9, PARP1 mRNA and Atg5, Atg7, Beclin1, LC3BⅡ, p62, LAMP2, Bax, cleaved Caspase3 (C-Caspase3), cleaved Caspase9 (C-Caspase9), cleaved PARP1 (C-PARP1) protein and the ratio of LC3BⅡ/LC3BⅠ in 50, 100 and 200 μg/ml carbon black exposure groups were significantly increased, while the relative expression levels of Bcl-2 mRNA and protein were significantly decreased (P<0.05). The changes of the above indexes were significantly correlated with the exposure dose of carbon black (r(s)=0.892, 0.879, 0.944, 0.892, 0.828, 0.880, 0.814, 0.794, 0.931, 0.918, 0.813, 0.866, 0.774, 0.695, 0.918, 0.761, 0.794, 0.944, 0.833, 0.866, 0.905, -0.886, -0.748, P<0.05). Compared with 100 μg/ml carbon black exposure group, the relative survival rate, the activities of SOD, GSH-Px and CAT in NAC+exposure group were significantly increased, while the levels of ROS and MDA were significantly decreased, and the relative expression levels of LC3B, p62 and Caspase3 mRNA and protein as well as the ratio of LC3BⅡ/LC3BⅠ were significantly decreased, and the differences were statistically significant (P<0.05). Compared with the control group, the apoptosis rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly increased (P<0.05), and there was a significant positive correlation between ultrafine carbon black exposure dose and cell apoptosis rate (r(s)=0.944, P<0.05). While compared with 100 μg/ml carbon black exposure group, the apoptosis rate of NAC+exposure group was significantly decreased, and the difference was statistically significant (P<0.05) . Conclusion: Cell autophagy and apoptosis may be important pathophysiological mechanisms of ultrafine carbon black-induced oxidative damage in BEAS-2B cells. NAC can alleviate the occurrence of BEAS-2B cell damage caused by ultrafine carbon black by regulating oxidative stress and the cascading autophagy and apoptosis pathways.},
}

Humans
*Acetylcysteine/pharmacology
*Apoptosis/drug effects
*Autophagy/drug effects
*Epithelial Cells/drug effects/metabolism
*Bronchi/cytology
*Soot/toxicity
*Oxidative Stress/drug effects
Cell Line
Reactive Oxygen Species/metabolism
Superoxide Dismutase/metabolism
Caspase 3/metabolism
Caspase 9/metabolism
Proto-Oncogene Proteins c-bcl-2/metabolism
Malondialdehyde/metabolism
Catalase/metabolism
bcl-2-Associated X Protein/metabolism/genetics
Glutathione Peroxidase/metabolism
Cell Survival/drug effects

@article {pmid39395220,
year = {2024},
author = {Xiang, RH and Wang, JQ and Li, ZG},
title = {Crosstalk of methylglyoxal and calcium signaling in maize (Zea mays L.) thermotolerance through methylglyoxal-scavenging system.},
journal = {Journal of plant physiology},
volume = {303},
number = {},
pages = {154362},
doi = {10.1016/j.jplph.2024.154362},
pmid = {39395220},
issn = {1618-1328},
mesh = {*Zea mays/physiology/drug effects/metabolism/genetics ; *Pyruvaldehyde/metabolism ; *Calcium Signaling ; *Thermotolerance/physiology ; Seedlings/physiology/drug effects ; Calcium/metabolism ; Heat-Shock Response/physiology ; Plant Proteins/metabolism/genetics ; Gene Expression Regulation, Plant/drug effects ; },
abstract = {Methylglyoxal (MG) and calcium ion (Ca[2+]) can increase multiple-stress tolerance including plant thermotolerance. However, whether crosstalk of MG and Ca[2+] exists in the formation of maize thermotolerance and underlying mechanism still remain elusive. In this paper, maize seedlings were irrigated with MG and calcium chloride alone or in combination, and then exposed to heat stress (HS). The results manifested that, compared with the survival percentage (SP, 45.3%) of the control seedlings, the SP of MG and Ca[2+] alone or in combination was increased to 72.4%, 74.2%, and 83.4% under HS conditions, indicating that Ca[2+] and MG alone or in combination could upraise seedling thermotolerance. Also, the MG-upraised SP was separately weakened to 42.2%, 40.3%, 52.1%, and 39.4% by Ca[2+] chelator (ethylene glycol tetraacetic acid, EGTA), plasma membrane Ca[2+] channel blocker (lanthanum chloride, LaCl3), intracellular Ca[2+] channel blocker (neomycin, NEC), and calmodulin (CaM) antagonist (trifluoperazine, TFP). However, significant effect of MG scavengers N-acetylcysteine (NAC) and aminoguanidine (AG) on Ca[2+]-induced thermotolerance was not observed. Similarly, an endogenous Ca[2+] level in seedlings was increased by exogenous MG under non-HS and HS conditions, while exogenous Ca[2+] had no significant effect on endogenous MG. These data implied that Ca[2+] signaling, at least partly, mediated MG-upraised thermotolerance in maize seedlings. Moreover, the activity and gene expression of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (MG reductase, aldehyde reductase, aldo-keto reductase, and lactate dehydrogenase) were up-regulated to a certain extent by Ca[2+] and MG alone in seedlings under non-HS and HS conditions. The up-regulated MG-scavenging system by MG was enhanced by Ca[2+], while impaired by EGTA, LaCl3, NEC, or TFP. These data suggest that the crosstalk of MG and Ca[2+] signaling in maize thermotolerance through MG-scavenging system. These findings provided a theoretical basis for breeding climate-resilient maize crop and developing smart agriculture.},
}

*Zea mays/physiology/drug effects/metabolism/genetics
*Pyruvaldehyde/metabolism
*Calcium Signaling
*Thermotolerance/physiology
Seedlings/physiology/drug effects
Calcium/metabolism
Heat-Shock Response/physiology
Plant Proteins/metabolism/genetics
Gene Expression Regulation, Plant/drug effects

@article {pmid39396855,
year = {2024},
author = {Gago, S and Diaz-Muñoz, J and Mogas, T},
title = {Impact of N-acetyl-L-cysteine on spindle morphology and reactive oxygen species in vitrified/warmed in vitro matured bovine oocytes.},
journal = {Reproduction in domestic animals = Zuchthygiene},
volume = {59 Suppl 3},
number = {},
pages = {e14619},
doi = {10.1111/rda.14619},
pmid = {39396855},
issn = {1439-0531},
support = {PID2020-116531RB-I00//Ministerio de Ciencia e Innovación/ ; 2021 SGR 00900//Generalitat de Catalunya/ ; },
mesh = {Animals ; Cattle ; *Acetylcysteine/pharmacology ; *Oocytes/drug effects ; *Reactive Oxygen Species/metabolism ; *In Vitro Oocyte Maturation Techniques/veterinary/methods ; *Vitrification ; Female ; *Spindle Apparatus/drug effects ; Antioxidants/pharmacology ; Cryopreservation/veterinary ; },
abstract = {Low developmental potential of vitrified in vitro matured (IVM) bovine oocytes is frequently attributed to high levels of reactive oxygen species (ROS) and abnormal spindle assembly. This study aimed to evaluate the efficacy of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, added to IVM medium in reducing ROS and preserving spindle configuration of vitrified/warmed IVM bovine oocytes. Oocytes collected from abattoir ovaries were either cultured in IVM medium or in IVM medium supplemented with 1 mM NAC for the initial 8 h of IVM. Half of the oocytes of each group were vitrified/warmed, and spindle morphology and ROS production were assessed at 24 h of IVM. Results indicated that fresh oocytes IVM with NAC improved spindle configuration, with significantly lower ROS levels compared to the control group. Vitrification resulted in lower percentages of bovine oocytes reaching the metaphase II stage but similar ROS levels to non-vitrified oocytes, regardless of NAC supplementation. However, the supplementation of NAC during maturation had no effect on spindle or chromosome configuration of vitrified oocytes. These findings emphasize NAC's potential in enhancing the quality of IVM bovine oocytes but its addition at 1 mM for 8 h to IVM medium did not decrease levels of ROS nor improve spindle assembly after vitrification.},
}

Animals
Cattle
*Acetylcysteine/pharmacology
*Oocytes/drug effects
*Reactive Oxygen Species/metabolism
*In Vitro Oocyte Maturation Techniques/veterinary/methods
*Vitrification
Female
*Spindle Apparatus/drug effects
Antioxidants/pharmacology
Cryopreservation/veterinary

@article {pmid39409186,
year = {2024},
author = {Lien, TS and Sun, DS and Wu, WS and Chang, HH},
title = {Dengue Envelope Protein as a Cytotoxic Factor Inducing Hemorrhage and Endothelial Cell Death in Mice.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
pmid = {39409186},
issn = {1422-0067},
support = {104-2320-B-320 -009 -MY3, 107-2311-B-320-002-MY3, 111-2320-B320-006-MY3, 112-2320-B-320-007//National Science and Technology Council, Taiwan/ ; TCMMP104-06, TCMMP108-04, TCMMP 111-01, TCAS111-02, TCAS-112-02, TCAS113-04, TCRD112-033, TCRD113-041//Tzu-Chi Medical Foundation/ ; },
mesh = {Animals ; Mice ; *Dengue Virus ; Humans ; *Endothelial Cells/drug effects/metabolism ; *Viral Envelope Proteins/metabolism ; *Apoptosis/drug effects ; *Severe Dengue/pathology/drug therapy ; *Hemorrhage/drug therapy ; Caspase 3/metabolism ; Disease Models, Animal ; Dengue/drug therapy/pathology ; Cell Line ; Cell Death/drug effects ; },
abstract = {Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis.},
}

Animals
Mice
*Dengue Virus
Humans
*Endothelial Cells/drug effects/metabolism
*Viral Envelope Proteins/metabolism
*Apoptosis/drug effects
*Severe Dengue/pathology/drug therapy
*Hemorrhage/drug therapy
Caspase 3/metabolism
Disease Models, Animal
Dengue/drug therapy/pathology
Cell Line
Cell Death/drug effects

@article {pmid39409801,
year = {2024},
author = {Ninković, M and Žutić, J and Tasić, A and Arsić, S and Bojkovski, J and Zdravković, N},
title = {An Innovative Approach: The Usage of N-Acetylcysteine in the Therapy of Pneumonia in Neonatal Calves.},
journal = {Animals : an open access journal from MDPI},
volume = {14},
number = {19},
pages = {},
pmid = {39409801},
issn = {2076-2615},
support = {451-03-66/2024-03/200030//This research was funded by the Serbian Ministry of Science, Technological Development and In-novation, grant numbers 451-03-66/2024-03/200030 and Collaborative Grant Scheme Program Call (ID: 50404) of the Innovation Found of The Republic of Serbia./ ; },
abstract = {NAC has mucolytic, antioxidant, and antimicrobial effects in living organisms. However, the therapeutic effects of NAC on clinical recovery among neonatal calves with respiratory diseases have not yet been studied. Our study represents the first investigation of the effects of NAC in neonatal calves with pneumonia. The objective of this work was to observe the effects of NAC in the treatment of neonatal pneumonia, including its ability to reduce the clinical score, shorten the duration of the treatment, and improve the overall health condition of neonatal calves. For this study, calves were divided into two groups: a treatment group that received NAC and amoxicillin with clavulanic acid, and a control group that received amoxicillin with clavulanic acid (antimicrobial only). The findings of this study indicate that NAC treatment significantly shortened the time to resolution (p < 0.001), compared to the results in the group without NAC treatment. Generally, NAC-supplemented therapy reduced the recovery time by more than 27 h (or slightly more than one day), compared to that in the antimicrobial-only group. Our study presents the first reported usage of NAC in therapy for respiratory disorders.},
}

@article {pmid39415242,
year = {2024},
author = {Fang, YQ and Ding, H and Li, T and Zhao, XJ and Luo, D and Liu, Y and Li, Y},
title = {N-acetylcysteine supplementation improves endocrine-metabolism profiles and ovulation induction efficacy in polycystic ovary syndrome.},
journal = {Journal of ovarian research},
volume = {17},
number = {1},
pages = {205},
pmid = {39415242},
issn = {1757-2215},
mesh = {*Polycystic Ovary Syndrome/drug therapy/metabolism ; Female ; *Acetylcysteine/pharmacology/therapeutic use ; Animals ; Mice ; Humans ; *Ovulation Induction/methods ; Adult ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Pregnancy ; Dietary Supplements ; Antioxidants/pharmacology/therapeutic use ; Ovary/drug effects/metabolism ; Metformin/pharmacology/therapeutic use ; Insulin Resistance ; Letrozole/pharmacology ; },
abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) affects 6-20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS.

METHODS: Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups.

RESULTS: Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005).

CONCLUSION: NAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS.},
}

*Polycystic Ovary Syndrome/drug therapy/metabolism
Female
*Acetylcysteine/pharmacology/therapeutic use
Animals
Mice
Humans
*Ovulation Induction/methods
Adult
Oxidative Stress/drug effects
Mice, Inbred C57BL
Pregnancy
Dietary Supplements
Antioxidants/pharmacology/therapeutic use
Ovary/drug effects/metabolism
Metformin/pharmacology/therapeutic use
Insulin Resistance
Letrozole/pharmacology

@article {pmid39420342,
year = {2024},
author = {Zhou, W and Qu, M and Yue, Y and Zhong, Z and Nan, K and Sun, X and Wu, Q and Zhang, J and Chen, W and Miao, C},
title = {Acetylcysteine synergizes PD-1 blockers against colorectal cancer progression by promoting TCF1[+]PD1[+]CD8[+] T cell differentiation.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {503},
pmid = {39420342},
issn = {1478-811X},
mesh = {Animals ; *Colorectal Neoplasms/pathology/drug therapy/immunology/metabolism ; *CD8-Positive T-Lymphocytes/immunology/drug effects ; *Cell Differentiation/drug effects ; *Programmed Cell Death 1 Receptor/metabolism/antagonists & inhibitors/immunology ; Mice ; *Acetylcysteine/pharmacology ; *Hepatocyte Nuclear Factor 1-alpha/metabolism/genetics ; *Disease Progression ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Humans ; Cell Line, Tumor ; Mice, Inbred C57BL ; Drug Synergism ; },
abstract = {BACKGROUND: Programmed cell death protein 1 (PD-1) blockade is essential in treating progressive colorectal cancer (CRC). However, some patients with CRC do not respond well to immunotherapy, possibly due to the exhaustion of CD8[+] T cells in the tumor microenvironment. N-Acetylcysteine (NAC) can reduce CD8[+] T cell exhaustion in vitro and induce their differentiation into long-lasting phenotypes, thus enhancing the anti-tumor effect of adoptive T cell transfer. However, whether NAC can be combined with PD-1 blockade in CRC treatment and how NAC regulates CD8[+] T cell differentiation remain unclear. Hence, in this study, we aimed to investigate whether NAC has a synergistic effect with PD-1 blockers against CRC progression.

METHODS: We constructed a mouse CRC model to study the effect of NAC on tumors. The effect of NAC on CD8 + T cell differentiation and its potential mechanism were explored using cell flow assay and other studies in vitro and ex vivo.

RESULTS: We demonstrated that NAC synergized PD-1 antibodies to inhibit CRC progression in a mouse CRC model mediated by CD8[+] T cells. We further found that NAC can induce TCF1[+]PD1[+]CD8[+] T cell differentiation and reduce the formation of exhausted T cells in vitro and in vivo. Moreover, NAC enhanced the expression of Glut4 in CD8[+] T cells, promoting the differentiation of TCF1[+]PD1[+]CD8[+] T cells.

CONCLUSIONS: Our study provides a novel idea for immunotherapy for clinically progressive CRC and suggests that Glut4 may be a new immunometabolic molecular target for regulating CD8[+] T cell differentiation.},
}

Animals
*Colorectal Neoplasms/pathology/drug therapy/immunology/metabolism
*CD8-Positive T-Lymphocytes/immunology/drug effects
*Cell Differentiation/drug effects
*Programmed Cell Death 1 Receptor/metabolism/antagonists & inhibitors/immunology
Mice
*Acetylcysteine/pharmacology
*Hepatocyte Nuclear Factor 1-alpha/metabolism/genetics
*Disease Progression
Immune Checkpoint Inhibitors/pharmacology/therapeutic use
Humans
Cell Line, Tumor
Mice, Inbred C57BL
Drug Synergism

@article {pmid39423623,
year = {2024},
author = {Liu, M and Gao, M and Shi, X and Yin, Y and Liu, H and Xie, R and Huang, C and Zhang, W and Xu, S},
title = {Quercetin attenuates SiO2-induced ZBP-1-mediated PANoptosis in mouse neuronal cells via the ROS/TLR4/NF-κb pathway.},
journal = {Journal of environmental management},
volume = {370},
number = {},
pages = {122948},
doi = {10.1016/j.jenvman.2024.122948},
pmid = {39423623},
issn = {1095-8630},
mesh = {Animals ; Mice ; *Silicon Dioxide/toxicity ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; *Quercetin/pharmacology ; *Reactive Oxygen Species/metabolism ; *Neurons/drug effects ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; },
abstract = {With the increasing development of the society, silicon dioxide (SiO2) has been used in various fields, such as agriculture, food industry, etc., and its residues can pose a potential health threat to organisms. Quercetin (Que) is a potent free radical scavenger commonly found in plants. C57BL/6 mice were chosen to established a mouse model of SiO2 exposure and Que antagonism to investigate the mechanism of action of Que in rescuing the toxic damage of SiO2 on mouse cerebellum tissue. The results showed that cytoplasmic vacuolization, and inflammatory cell infiltration caused by SiO2 were alleviated by the addition of Que, and reduced oxidative stress in mouse cerebellum, alleviated the activation of TLR4 pathway induced by SiO2, and substantially reduced the occurrence of ZBP-1-mediated PANoptosis induced by SiO2 exposure in mouse cerebellum. In NS20Y cells, the oxidative stress activator (Elesclomol) and inhibitor N-acetyl cysteine (NAC), and the NF-κB activator 2 (NA2) were added. Elesclomol and NAC confirm the involvement of ROS in regulating the TLR4/NF-κB pathway, the TLR4/NF-κB pathway regulated ZBP-1-mediated PANoptosis in cerebellum and NS20Y cells induced by SiO2 exposure. In conclusion, the present experimental data suggest that Que mitigates the onset of ZBP-1-mediated PANoptosis in neuronal cells induced by SiO2 through the ROS/TLR4/NF-κB pathway. The present experimental findings help to understand the detoxification effect of Que in more tissues and provide an important reference for the rescue of organisms in long-term SiO2 environment.},
}

Animals
Mice
*Silicon Dioxide/toxicity
*Toll-Like Receptor 4/metabolism
*NF-kappa B/metabolism
*Quercetin/pharmacology
*Reactive Oxygen Species/metabolism
*Neurons/drug effects
Oxidative Stress/drug effects
Mice, Inbred C57BL
Signal Transduction/drug effects

@article {pmid39430194,
year = {2024},
author = {Hernández-Cruz, EY and Aparicio-Trejo, OE and Hammami, FA and Bar-Shalom, D and Tepel, M and Pedraza-Chaverri, J and Scholze, A},
title = {N-acetylcysteine in Kidney Disease: Molecular Mechanisms, Pharmacokinetics, and Clinical Effectiveness.},
journal = {Kidney international reports},
volume = {9},
number = {10},
pages = {2883-2903},
pmid = {39430194},
issn = {2468-0249},
abstract = {N-acetylcysteine (NAC) has shown beneficial effects in both acute kidney disease and chronic kidney disease (CKD) in preclinical and clinical studies. Different dosage and administration forms of NAC have specific pharmacokinetic properties that determine the temporal pattern of plasma concentrations of NAC and its active metabolites. Especially in acute situations with short-term NAC administration, appropriate NAC and glutathione (GSH) plasma concentrations should be timely ensured. For oral dosage forms, bioavailability needs to be established for the respective NAC formulation. Kidney function influences NAC pharmacokinetics, including a reduction of NAC clearance in advanced CKD. In addition, mechanisms of action underlying beneficial NAC effects depend on kidney function as well as comorbidities, both involving GSH deficiency, alterations in nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent signaling, oxidative stress, mitochondrial dysfunction, and disturbed mitochondrial bioenergetics. This also applies to nonrenal NAC mechanisms. The timing of preventive NAC administration in relation to potential injury is important. NAC administration seems most effective either preceding, or preceding and paralleling conditions that induce tissue damage. Furthermore, studies suggest that very high concentrations of NAC should be avoided because they could exert reductive stress. Delayed administration of NAC might interfere with endogenous repair mechanisms. In conclusion, studies on NAC treatment regimens need to account for both NAC pharmacokinetics and NAC molecular effects. Kidney function of the patient population and pathomechanisms of the kidney disease should guide rational NAC trial design. A targeted trial approach and biomarker-guided protocols could pave the way for the use of NAC in precision medicine.},
}

@article {pmid39436429,
year = {2025},
author = {Galicia-Moreno, M and Monroy-Ramirez, HC and Caloca-Camarena, F and Arceo-Orozco, S and Muriel, P and Sandoval-Rodriguez, A and García-Bañuelos, J and García-González, A and Navarro-Partida, J and Armendariz-Borunda, J},
title = {A new opportunity for N-acetylcysteine. An outline of its classic antioxidant effects and its pharmacological potential as an epigenetic modulator in liver diseases treatment.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {398},
number = {3},
pages = {2365-2386},
pmid = {39436429},
issn = {1432-1912},
mesh = {*Acetylcysteine/pharmacology/therapeutic use ; Humans ; *Antioxidants/pharmacology/therapeutic use/adverse effects ; *Epigenesis, Genetic/drug effects ; *Liver Diseases/drug therapy/genetics/metabolism ; Animals ; Oxidative Stress/drug effects ; },
abstract = {Liver diseases represent a worldwide health problem accountable for two million deaths per year. Oxidative stress is critical for the development of these diseases. N-acetyl cysteine (NAC) is effective in preventing liver damage, both in experimental and clinical studies, and evidence has shown that the pharmacodynamic mechanisms of NAC are related to its antioxidant nature and ability to modulate key signaling pathways. Here, we provide a comprehensive description of the beneficial effects of NAC in the treatment of liver diseases, addressing the first evidence of its role as a scavenger and precursor of reduced glutathione, along with studies showing its immunomodulatory action, as well as the ability of NAC to modulate epigenetic hallmarks. We searched the PubMed database using the following keywords: oxidative stress, liver disease, epigenetics, antioxidants, NAC, and antioxidant therapies. There was no time limit to gather all available information on the subject. NAC has shown efficacy in treating liver damage, exerting mechanisms of action different from those of free radical scavengers. Like different antioxidant therapies, its effectiveness and safety are related to the administered dose; therefore, designing new pharmacological formulations for this drug is imperative to achieve an adequate response. Finally, there is still much to explore regarding its effect on epigenetic marker characteristics of liver damage, turning it into a drug with broad therapeutic potential. According to the literature reviewed, NAC could be an appropriate option in clinical studies related to hepatic injury and, in the future, a repurposing alternative for treating liver diseases.},
}

*Acetylcysteine/pharmacology/therapeutic use
Humans
*Antioxidants/pharmacology/therapeutic use/adverse effects
*Epigenesis, Genetic/drug effects
*Liver Diseases/drug therapy/genetics/metabolism
Animals
Oxidative Stress/drug effects

@article {pmid39447843,
year = {2024},
author = {Zheng, M and Song, W and Huang, P and Huang, Y and Lin, H and Zhang, M and He, H and Wu, J},
title = {Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {376},
number = {},
pages = {701-716},
doi = {10.1016/j.jconrel.2024.10.046},
pmid = {39447843},
issn = {1873-4995},
mesh = {Animals ; *Wound Healing/drug effects ; *Fibroblast Growth Factor 2/administration & dosage/chemistry ; *Hydrogels/chemistry/administration & dosage ; *Acetylcysteine/administration & dosage ; Antioxidants/administration & dosage/chemistry/pharmacology ; Male ; Diabetes Mellitus, Experimental/drug therapy ; Oxidative Stress/drug effects ; Drug Liberation ; Rats, Sprague-Dawley ; Mice ; Cross-Linking Reagents/chemistry ; },
abstract = {Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and N-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) via thiol-disulfide exchange reactions. In response to oxidative stress (e.g., reactive oxygen species), the disulfide bonds (SS) within the hydrogel are broken into thiol groups (-S-H), thereby promoting hydrogel degradation and enabling controlled drug release. Initially, NAC is released to scavenge free radicals and ameliorate oxidative damage. Subsequently, bFGF is released to expedite tissue regeneration. This combinatorial strategy is tailored to the specific characteristics of the wound microenvironment at various stages of diabetic wound healing, thereby achieving therapeutic efficacy. The results indicate that the bFGF-HSPP-NAC hydrogel markedly enhances re-epithelialization, collagen deposition, hair follicle regeneration, and neovascularization. In conclusion, the bioresponsive bFGF-HSPP-NAC hydrogel demonstrates significant potential for application in combinatorial therapeutic approaches for diabetic wound healing.},
}

Animals
*Wound Healing/drug effects
*Fibroblast Growth Factor 2/administration & dosage/chemistry
*Hydrogels/chemistry/administration & dosage
*Acetylcysteine/administration & dosage
Antioxidants/administration & dosage/chemistry/pharmacology
Male
Diabetes Mellitus, Experimental/drug therapy
Oxidative Stress/drug effects
Drug Liberation
Rats, Sprague-Dawley
Mice
Cross-Linking Reagents/chemistry

@article {pmid39450216,
year = {2024},
author = {Yahia, Z and Yahia, A and Abdelaziz, T},
title = {N-acetylcysteine Clinical Applications.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e72252},
pmid = {39450216},
issn = {2168-8184},
abstract = {This study aims to evaluate the therapeutic application of N-acetylcysteine (NAC) as a treatment or adjunct therapy for various medical conditions. While its efficacy in treating acetaminophen overdose, cystic fibrosis, and chronic obstructive pulmonary disease is well-established, emerging evidence suggests that NAC may also benefit a broader spectrum of illnesses due to its safety, simplicity, and affordability. A comprehensive review was conducted by searching PubMed, relevant books, and conference proceedings for publications discussing NAC about the specified health conditions. The clinically relevant data were analysed using the American Family Physician Evidence-Based Medicine Toolkit, following a standard integrated review methodology. NAC shows potential as an adjunctive treatment for a wide range of medical conditions, particularly chronic diseases. It may be beneficial for polycystic ovary syndrome, endometriosis, male infertility, cataracts, glaucoma, dry eye syndrome, parkinsonism, multiple sclerosis, Alzheimer's disease, stroke outcomes, non-acetaminophen-induced acute liver failure, Crohn's disease, ulcerative colitis, schizophrenia, bipolar disorder, and obsessive-compulsive disorder. Although evidence for some conditions is less robust, NAC's therapeutic potential warrants further investigation. Given the aging population and the decline in glutathione levels, the use of NAC should be considered across a variety of medical conditions. This paper suggests that NAC supplementation could play a significant role in reducing morbidity and mortality associated with numerous chronic diseases.},
}

@article {pmid39452251,
year = {2024},
author = {Recinella, L and Pinti, M and Libero, ML and Di Lodovico, S and Veschi, S and Piro, A and Generali, D and Acquaviva, A and Nilofar, N and Orlando, G and Chiavaroli, A and Ferrante, C and Menghini, L and Di Simone, SC and Brunetti, L and Di Giulio, M and Leone, S},
title = {Beneficial Effects Induced by a Proprietary Blend of a New Bromelain-Based Polyenzymatic Complex Plus N-Acetylcysteine in Urinary Tract Infections: Results from In Vitro and Ex Vivo Studies.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
pmid = {39452251},
issn = {2079-6382},
abstract = {Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO[®]) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies.},
}

@article {pmid39456416,
year = {2024},
author = {Yun, HM and Kim, SH and Kwon, YJ and Park, KR},
title = {Effect of Spicatoside a on Anti-Osteosarcoma MG63 Cells through Reactive Oxygen Species Generation and the Inhibition of the PI3K-AKT-mTOR Pathway.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
pmid = {39456416},
issn = {2076-3921},
support = {K412000//Korea Basic Science Institute/ ; 2022R1C1C1003491//National Research Foundation of Korea/ ; },
abstract = {Osteosarcoma is a primary malignant tumor found in the bones of children and adolescents. Unfortunately, many patients do not respond well to treatment and succumb to the illness. Therefore, it is necessary to discover novel bioactive compounds to overcome therapeutic limitations. Liriope platyphylla Wang et Tang is a well-known herb used in oriental medicine. Studies have shown that metabolic diseases can be clinically treated using the roots of L. platyphylla. Recent studies have demonstrated the anticarcinoma potential of root extracts; however, the exact mechanism remains unclear. The aim of this study was to examine the anti-osteosarcoma activity of a single compound extracted from the dried roots of L. platyphylla. We purified Spicatoside A (SpiA) from the dried roots of L. platyphylla. SpiA significantly inhibited the proliferation of human osteosarcoma MG63 cells in a dose- and time-dependent manner. SpiA also regulated the expression of various downstream proteins that mediate apoptosis (PARP, Bcl-2, and Bax), cell growth (cyclin D1, Cdk4, and Cdk6), angiogenesis (VEGF), and metastasis (MMP13). The Proteome Profiler Human Phospho-Kinase Array Kit showed that the AKT signaling protein was a target of SpiA in osteosarcoma cells. We also found that SpiA suppressed the constitutive activation of the PI3K-AKT-mTOR-p70S6K1 signaling pathway. We further validated the effects of SpiA on the AKT signaling pathway. SpiA induced autophagosome formation and suppressed necroptosis (a form of programmed cell death). SpiA increased the generation of reactive oxygen species (ROS) and led to the loss of mitochondrial membrane potential. N-acetylcysteine (NAC)-induced inhibition of ROS generation reduced SpiA-induced AKT inhibition, apoptotic cell death, and anti-metastatic effects by suppressing cell migration and invasion. Overall, these results highlight the anti-osteosarcoma effect of SpiA by inhibiting the AKT signaling pathway through ROS generation, suggesting that SpiA may be a promising compound for the treatment of human osteosarcoma.},
}

@article {pmid39461063,
year = {2025},
author = {Jin, Y and Zhang, J and Chen, X and Li, F and Xue, T and Yi, K and Xu, Y and Wang, H and Lao, YH and Chan, HF and Shao, D and Li, M and Tao, Y},
title = {3D printing incorporating gold nanozymes with mesenchymal stem cell-derived hepatic spheroids for acute liver failure treatment.},
journal = {Biomaterials},
volume = {315},
number = {},
pages = {122895},
doi = {10.1016/j.biomaterials.2024.122895},
pmid = {39461063},
issn = {1878-5905},
mesh = {*Gold/chemistry ; *Liver Failure, Acute/therapy ; *Printing, Three-Dimensional ; *Mesenchymal Stem Cells/cytology ; *Spheroids, Cellular/drug effects ; Animals ; *Hydrogels/chemistry ; Hepatocytes/cytology/drug effects ; Metal Nanoparticles/chemistry ; Humans ; Reactive Oxygen Species/metabolism ; Male ; Tissue Scaffolds/chemistry ; Mice ; Alginates/chemistry ; },
abstract = {Acute liver failure (ALF) is a highly fatal disease, necessitating the advancement and optimization of alternative therapeutic strategies to benefit patients awaiting liver transplantation. In this study, we innovatively established the antioxidant nanozyme-hepatocyte-like cells (HLCs) microtissue sheets (HS/N-Au@composite) for ALF therapy. We first prepared a 3D-printed hyaluronic acid/gelatin/sodium alginate scaffold with N-acetylcysteine (NAC)-capped gold nanoclusters (NAC-Au NCs), forming the N-Au@hydrogel. For the encapsulation of HLC spheroids, we used a biocompatible hybrid hydrogel composed of decellularized extracellular matrix (dECM), thrombin, and fibrinogen, resulting in the HS@dECM hydrogel. Utilizing 3D printing technology, we integrated the N-Au@hydrogel with the HS@dECM hydrogel to create the HS/N-Au@composite for in situ transplantation to treat ALF. Our results demonstrated that NAC-Au NCs effectively mitigated reactive oxygen species (ROS)-induced liver necrosis in ALF. Additionally, the N-Au@hydrogel provided mechanical support, ensuring the proper landing and effective functioning of the transplanted HLC spheroids. The HS/N-Au@composite synergistically decreased serum transaminase levels, reduced the accumulation of pro-inflammatory cytokines, accelerated liver function recovery, and promoted liver regeneration in ALF treatment. This combination of HLC spheroids and NAC-Au NCs nanozymes via 3D-printed composite scaffolds represents a promising strategy for enhancing hepatocyte transplantation and advancing stem cell regenerative medicine in ALF therapy.},
}

*Gold/chemistry
*Liver Failure, Acute/therapy
*Printing, Three-Dimensional
*Mesenchymal Stem Cells/cytology
*Spheroids, Cellular/drug effects
Animals
*Hydrogels/chemistry
Hepatocytes/cytology/drug effects
Metal Nanoparticles/chemistry
Humans
Reactive Oxygen Species/metabolism
Male
Tissue Scaffolds/chemistry
Mice
Alginates/chemistry

@article {pmid39467998,
year = {2024},
author = {Zhang, M and Dai, GC and Zhang, YW and Lu, PP and Wang, H and Li, YJ and Rui, YF},
title = {Enhancing osteogenic differentiation of diabetic tendon stem/progenitor cells through hyperoxia: Unveiling ROS/HIF-1α signalling axis.},
journal = {Journal of cellular and molecular medicine},
volume = {28},
number = {20},
pages = {e70127},
pmid = {39467998},
issn = {1582-4934},
support = {BK20221462//Natural Science Foundation of Jiangsu Province/ ; No.81871812//National Natural Science Foundation of China/ ; YL20220525//Winfast Charity Foundation Project/ ; CZXM-GSP-RC46//Research Personnel Cultivation Programme of Zhongda Hospital Southeast University/ ; },
mesh = {*Osteogenesis ; Animals ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Reactive Oxygen Species/metabolism ; *Stem Cells/metabolism/cytology ; *Signal Transduction ; *Cell Differentiation ; Rats ; *Tendons/metabolism/pathology ; Male ; *Diabetes Mellitus, Experimental/metabolism/pathology ; Rats, Sprague-Dawley ; Hyperoxia/metabolism ; Acetylcysteine/pharmacology ; },
abstract = {Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy.},
}

*Osteogenesis
Animals
*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics
*Reactive Oxygen Species/metabolism
*Stem Cells/metabolism/cytology
*Signal Transduction
*Cell Differentiation
Rats
*Tendons/metabolism/pathology
Male
*Diabetes Mellitus, Experimental/metabolism/pathology
Rats, Sprague-Dawley
Hyperoxia/metabolism
Acetylcysteine/pharmacology

@article {pmid39469595,
year = {2024},
author = {Khoury, RD and Abu Hasna, A and Gagliardi, CF and Marinho, RMM and Carvalho, CAT and Bresciani, E and Valera, MC},
title = {Antimicrobial and anti-endotoxin activity of N-acetylcysteine, calcium hydroxide and their combination against Enterococcus faecalis, Escherichia coli and lipopolysaccharides.},
journal = {PeerJ},
volume = {12},
number = {},
pages = {e18331},
pmid = {39469595},
issn = {2167-8359},
mesh = {*Enterococcus faecalis/drug effects ; *Calcium Hydroxide/pharmacology ; *Acetylcysteine/pharmacology ; *Escherichia coli/drug effects ; Humans ; *Lipopolysaccharides/pharmacology ; Dental Pulp Cavity/microbiology/drug effects ; Anti-Infective Agents/pharmacology ; Biofilms/drug effects ; Anti-Bacterial Agents/pharmacology ; Root Canal Irrigants/pharmacology ; },
abstract = {BACKGROUND: The management of endodontic infections is a complex challenge, mainly due to the involvement of diverse microorganisms and their by-products. This study aimed to evaluate the efficacy of N-acetylcysteine (NAC), calcium hydroxide (Ca(OH)2), and their combined application as intracanal medications in combating Enterococcus faecalis, Escherichia coli, and lipopolysaccharides (LPS) from E. coli.

METHODS: A total of 60 single-rooted human teeth were carefully selected and divided into six groups. These tooth canals were deliberately exposed to E. faecalis (ATCC 29212) and E. coli (ATCC 25922) to induce biofilm formation. Subsequently, the specimens were treated with NAC, Ca(OH)2, or a combination of both substances. Three samples of the root canals were collected at three moments: the first sample (S1) was to confirm the initial contamination, the second sample (S2) was immediately post-instrumentation, and the third sample (S3) was collected after the use of the intracanal medication. The antimicrobial efficacy of these intracanal medications was assessed by enumerating colony-forming units per milliliter (CFU/mL). In addition to this, the kinetic chromogenic Limulus Amebocyte Lysate (LAL) assay by Lonza was used to quantify LPS from E. coli. Data tested for normality; then, Kruskal-Wallis and Friedman tests were used, and Dunn's for multiple comparisons.

RESULTS: The findings of this study showed significant reductions in the microbial load of E. faecalis and E. coli by S3. Notably, there were no statistically significant differences among the treatment groups concerning these microorganisms. However, it was observed that only the combination of NAC and Ca(OH)2 led to a noteworthy decrease in the quantity of E. coli's LPS after 7-days, demonstrating a statistically significant difference from the other treatment groups. NAC + Ca(OH)2 combination, applied for a duration of 7-days, proved to be more suitable in reducing the presence of E. faecalis, E. coli, and LPS from E. coli within the context of endodontic infections.},
}

*Enterococcus faecalis/drug effects
*Calcium Hydroxide/pharmacology
*Acetylcysteine/pharmacology
*Escherichia coli/drug effects
Humans
*Lipopolysaccharides/pharmacology
Dental Pulp Cavity/microbiology/drug effects
Anti-Infective Agents/pharmacology
Biofilms/drug effects
Anti-Bacterial Agents/pharmacology
Root Canal Irrigants/pharmacology

@article {pmid39471200,
year = {2024},
author = {Quintanilla, ME and Morales, P and Santapau, D and Gallardo, J and Rebolledo, R and Riveras, G and Acuña, T and Herrera-Marschitz, M and Israel, Y and Ezquer, F},
title = {Morphine self-administration is inhibited by the antioxidant N-acetylcysteine and the anti-inflammatory ibudilast; an effect enhanced by their co-administration.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0312828},
pmid = {39471200},
issn = {1932-6203},
mesh = {Animals ; *Acetylcysteine/pharmacology/administration & dosage ; *Antioxidants/pharmacology/administration & dosage ; *Rats, Wistar ; Rats ; *Morphine/pharmacology/administration & dosage ; Male ; *Oxidative Stress/drug effects ; *Pyridines/pharmacology/administration & dosage ; *Self Administration ; *Anti-Inflammatory Agents/pharmacology/administration & dosage ; Morphine Dependence/drug therapy/metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Hippocampus/metabolism/drug effects ; Nucleus Accumbens/metabolism/drug effects ; Indolizines ; Pyrazoles ; },
abstract = {BACKGROUND: The treatment of opioid addiction mainly involves the medical administration of methadone or other opioids, aimed at gradually reducing dependence and, consequently, the need for illicit opioid procurement. Thus, initiating opioid maintenance therapy with a lower level of dependence would be advantageous. There is compelling evidence indicating that opioids induce brain oxidative stress and associated glial activation, resulting in the dysregulation of glutamatergic homeostasis, which perpetuates drug intake. The present study aimed to determine whether inhibiting oxidative stress and/or neuroinflammation reduces morphine self-administration in an animal model of opioid dependence.

METHODS: Morphine dependence, assessed as voluntary morphine self-administration, was evaluated in Wistar-derived UChB rats. Following an extended period of morphine self-administration, animals were administered either the antioxidant N-acetylcysteine (NAC; 40 mg/kg/day), the anti-inflammatory ibudilast (7.5 mg/kg/day) or the combination of both agents. Oxidative stress and neuroinflammation were evaluated in the hippocampus, a region involved in drug recall that feeds into the nucleus accumbens, where the levels of the glutamate transporters GLT-1 and xCT were further assessed.

RESULTS: Daily administration of either NAC or ibudilast led to a mild reduction in voluntary morphine intake, while the co-administration of both therapeutic agents resulted in a marked inhibition (-57%) of morphine self-administration. The administration of NAC or ibudilast markedly reduced both the oxidative stress induced by chronic morphine intake and the activation of microglia and astrocytes in the hippocampus. However, only the combined administration of NAC + ibudilast was able to restore the normal levels of the glutamate transporter GLT-1 in the nucleus accumbens.

CONCLUSION: Separate or joint administration of an antioxidant and anti-inflammatory agent reduced voluntary opioid intake, which could have translational value for the treatment of opioid use disorders, particularly in settings where the continued maintenance of oral opioids is a therapeutic option.},
}

Animals
*Acetylcysteine/pharmacology/administration & dosage
*Antioxidants/pharmacology/administration & dosage
*Rats, Wistar
Rats
*Morphine/pharmacology/administration & dosage
Male
*Oxidative Stress/drug effects
*Pyridines/pharmacology/administration & dosage
*Self Administration
*Anti-Inflammatory Agents/pharmacology/administration & dosage
Morphine Dependence/drug therapy/metabolism
Excitatory Amino Acid Transporter 2/metabolism
Hippocampus/metabolism/drug effects
Nucleus Accumbens/metabolism/drug effects
Indolizines
Pyrazoles

@article {pmid39472133,
year = {2024},
author = {Li, WK and Zhang, Y and Qu, XY and Lin, YQ and Zhao, YZ and Liu, N},
title = {[N-acetylcysteine regulates NF-κB signaling pathway alleviates the pulmonary toxicity induced by indium-tin oxide nanoparticles in rats].},
journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases},
volume = {42},
number = {10},
pages = {721-729},
doi = {10.3760/cma.j.cn121094-20230919-00061},
pmid = {39472133},
issn = {1001-9391},
support = {H2024209031//Natural Science Foundation of Hebei Province/ ; 24130225C//Tangshan Science and Technology Project/ ; },
mesh = {Animals ; Rats ; Male ; *NF-kappa B/metabolism ; *Rats, Sprague-Dawley ; *Signal Transduction/drug effects ; *Acetylcysteine/pharmacology ; *Tin Compounds/toxicity ; *Oxidative Stress/drug effects ; *Lung/metabolism/drug effects/pathology ; Nanoparticles/toxicity ; Pulmonary Alveolar Proteinosis/metabolism ; },
abstract = {Objective: The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling. Methods: In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed. Results: Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased (P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased (P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased (P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased (P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased (P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased (P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased (P<0.05) . Conclusion: The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.},
}

Animals
Rats
Male
*NF-kappa B/metabolism
*Rats, Sprague-Dawley
*Signal Transduction/drug effects
*Acetylcysteine/pharmacology
*Tin Compounds/toxicity
*Oxidative Stress/drug effects
*Lung/metabolism/drug effects/pathology
Nanoparticles/toxicity
Pulmonary Alveolar Proteinosis/metabolism

@article {pmid39473642,
year = {2024},
author = {Mendes Abreu, J and Quitério, A and Cerqueira, É and Ribeiro, R and Nunes, T and Figueiredo, JP and Corte Real, A},
title = {Evaluating the Impact of Different Treatments on the Quality of Life in Patients With Burning Mouth Syndrome: A Scoping Review.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e70419},
pmid = {39473642},
issn = {2168-8184},
abstract = {The profound impact of burning mouth syndrome (BMS) on patients' quality of life (QoL) highlights the critical need to identify effective treatments for this condition. This study aims to evaluate and compare the health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) among individuals diagnosed with BMS, focusing on different treatment modalities. For that purpose, a scoping review was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for scoping review reporting guidelines and the registration with the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search was then conducted in March 2024, encompassing the following databases: PubMed, Embase, Cochrane, Web of Science, and Trip Database. Publications were deemed eligible if they assessed the impact of different treatments for BMS on health-related and oral health-related QoL. Out of the initial 5400, only 13 studies were considered suitable to be included in this review. The instrument used to evaluate HRQoL was the 36-Item Short Form Survey (SF-36). For OHRQoL, the preferred tools were the Oral Health Impact Profile (OHIP) and the Geriatric Oral Health Assessment Index (GOHAI). Literature reported improvements in patients' HRQoL across the majority of analyzed treatment modalities. However, low-level laser therapy (LLLT) and n-acetylcysteine (NAC) plus clonazepam were the most effective in improving OHRQoL. This review highlights several promising treatment options for improving both HRQoL and OHRQoL in individuals with BMS. Nevertheless, the variability among the studies analyzed underscores the need for further research to identify and establish consistently effective treatments for this condition, reflecting the need for consistent trial designs to accurately assess the true impact of treatments on the disease.},
}

@article {pmid39474327,
year = {2024},
author = {Guo, Y and Yang, Y and Zhou, Z and Zhao, C and Li, Y and Zhou, H and Ren, S and Gu, Y and Gao, Z},
title = {Propylparaben Induces Reproductive Toxicity in Human Extravillous Trophoblast Cells via Apoptosis and Cell Cycle Pathways.},
journal = {Environment & health (Washington, D.C.)},
volume = {2},
number = {5},
pages = {301-310},
pmid = {39474327},
issn = {2833-8278},
abstract = {Parabens (PBs), especially propylparaben, commonly used in consumer products, pose environmental and health concerns. This study explored propylparaben's cytotoxicity on HTR-8/SVneo human trophoblast cells, revealing significant dose-dependent cytotoxic effects, particularly post 48-h exposure. Elevated propylparaben levels triggered apoptosis, evidenced by increased Bax and activated Caspase-3, and induced the G0/G1 cell cycle arrest. Concurrently, an increase in reactive oxygen species and reduced mitochondrial membrane potential indicated oxidative stress and mitochondrial dysfunction. Although N-acetylcysteine (NAC) treatment reduced oxidative stress, cell invasiveness persisted, suggesting propylparaben might affect cell migration through nonoxidative mechanisms. Integrated transcriptome analysis through RNA sequencing revealed 3488 differentially expressed genes affected by propylparaben, highlighting changes in pathways like apoptosis and cell cycle regulation and identifying seven hub genes as potential biomarkers for pregnancy-related complications. This study comprehensively demonstrates the cytotoxic effects of propylparaben on human trophoblast cells, notably through apoptosis induction and cell cycle disruption, thereby providing crucial insights into its potential risks for reproductive health.},
}

@article {pmid39478327,
year = {2025},
author = {Ma, Y and Chen, M and Huang, K and Chang, W},
title = {The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis.},
journal = {Aging cell},
volume = {24},
number = {2},
pages = {e14392},
pmid = {39478327},
issn = {1474-9726},
support = {MYRG2022-00251-FHS//Universidade de Macau/ ; 0061/2022/A//Fundo para o Desenvolvimento das Ciências e da Tecnologia/ ; 0077/2020/A2//Fundo para o Desenvolvimento das Ciências e da Tecnologia/ ; 0099/2022/AFJ//Fundo para o Desenvolvimento das Ciências e da Tecnologia/ ; },
mesh = {Animals ; *Cysteine/pharmacology ; *Longevity/drug effects ; *Caenorhabditis elegans/drug effects/physiology ; Mice ; Drosophila ; Models, Animal ; Humans ; Dietary Supplements ; },
abstract = {Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N-acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti-aging effects of cysteine, we systematically reviewed and performed a meta-analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine.},
}

Animals
*Cysteine/pharmacology
*Longevity/drug effects
*Caenorhabditis elegans/drug effects/physiology
Mice
Drosophila
Models, Animal
Humans
Dietary Supplements

@article {pmid39479839,
year = {2024},
author = {Yang, B and Zhao, LL and DU, JH and Yan, Y and Dai, KS},
title = {[Regulation of Reactive Oxygen Species on Platelet Activation and Apoptosis].},
journal = {Zhongguo shi yan xue ye xue za zhi},
volume = {32},
number = {5},
pages = {1503-1508},
doi = {10.19746/j.cnki.issn.1009-2137.2024.05.031},
pmid = {39479839},
issn = {1009-2137},
mesh = {*Reactive Oxygen Species/metabolism ; *Apoptosis/drug effects ; Humans ; *Blood Platelets/metabolism ; *Membrane Potential, Mitochondrial ; *Platelet Activation ; *P-Selectin/metabolism ; *Thrombin/pharmacology ; *Platelet Aggregation ; Signal Transduction ; Acetylcysteine/pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; },
abstract = {OBJECTIVE: To investigate how reactive oxygen species (ROS) regulates the signal transduction of platelet activation and apoptosis, and to explore the relationship between platelet activation and apoptosis.

METHODS: Platelets were directly stimulated with thrombin or pretreated with ROS inhibitor N-acetylcysteine (NAC) before being stimulated with thrombin, and then flow cytometry was used to detect the effects of thrombin and NAC on P-selectin expression, αⅡbβ3 activation, mitochondrial membrane potential depolarization, phosphatidylserine (PS) externalization, ROS expression and platelet aggregation.

RESULTS: Thrombin could induce the production of ROS in platelets in a concentration- and time-dependent manner. 0.01 U thrombin induced ROS-dependent high degree of integrin αⅡbβ3 activation, P-selectin expression, and platelet aggregation. The platelets induced by different concentration gradients of thrombin exhibited ROS-dependent mitochondrial membrane potential depolarization and PS externalization in platelets. After induction with thrombin for 30 min, the activation of integrin αⅡbβ3 in platelets reached its maximum level, and after 60 minutes, the depolarization of mitochondrial membrane potential in platelets reached its maximum level. However, the expression of P-selectin, depolarization of mitochondrial membrane potential, and platelet aggregation function were all inhibited to a certain extent when the platelets were pretreated with ROS inhibitor NAC and then induced with thrombin.

CONCLUSION: When platelets are induced by thrombin, ROS first regulates the activation of platelets, and then regulates the apoptosis of platelets. Both platelet activation and apoptosis depend on the production of ROS in platelets, and the signals of activation and apoptosis occur orderly. Inhibiting the ROS signal in platelets can effectively inhibit the activation and apoptosis of platelets.},
}

*Reactive Oxygen Species/metabolism
*Apoptosis/drug effects
Humans
*Blood Platelets/metabolism
*Membrane Potential, Mitochondrial
*Platelet Activation
*P-Selectin/metabolism
*Thrombin/pharmacology
*Platelet Aggregation
Signal Transduction
Acetylcysteine/pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex/metabolism

@article {pmid39488036,
year = {2024},
author = {Joseph, JP and Kumar, T and Ramteke, NS and Chatterjee, K and Nandi, D},
title = {High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells: Tert-butyl hydroquinone as an additive enhancer of intracellular calcium.},
journal = {International immunopharmacology},
volume = {143},
number = {Pt 3},
pages = {113501},
doi = {10.1016/j.intimp.2024.113501},
pmid = {39488036},
issn = {1878-1705},
mesh = {Animals ; *Hydroquinones/pharmacology ; *Calcium/metabolism ; *Cell Proliferation/drug effects ; *T-Lymphocytes/drug effects/immunology/metabolism ; Mice ; *Lymphocyte Activation/drug effects ; *Reactive Oxygen Species/metabolism ; Mice, Inbred C57BL ; Colitis/drug therapy/chemically induced/immunology ; Cells, Cultured ; Ionomycin/pharmacology ; Dextran Sulfate ; NF-E2-Related Factor 2/metabolism/genetics ; Tetradecanoylphorbol Acetate/pharmacology ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism/genetics ; Female ; },
abstract = {Optimal T cell activation is critical to orchestrate adaptive immune responses. Calcium is critical for T cell activation and integrates signaling pathways necessary to activate key transcription factors. In fact, patients with calcium channelopathies are immunodeficient. Here, we investigated the effects of different concentrations of intracellular calcium on activation of mouse T cells. High intracellular calcium amounts inhibited in vitro T cell proliferation as evidenced by a decreased cell cycling-to-hypodiploidy ratio in two models of activation: the combination of phorbol 12-myristate 13-acetate (PMA) and Ionomycin (an ionophore)/Thapsigargin (a SERCA inhibitor) or plate bound anti-CD3 and anti-CD28. High intracellular calcium amounts increased the production of reactive oxygen species (ROS) in T cells activated with PMA and Ionomycin and scavenging excess ROS using N-acetyl cysteine (NAC) rescued the decrease in cycling-to-hypodiploidy ratio. To test the universality of our observations, we studied the effects of tert-Butylhydroquinone (tBHQ), a SERCA inhibitor and Nrf2 activator. tBHQ alone did not increase intracellular calcium amounts but the intracellular calcium amounts increased when tBHQ was used in combination with PMA. Also, tBHQ inhibited T cell activation in a dose-dependent manner in both in vitro models of T cell activation. Importantly, intraperitoneal injection of tBHQ ameliorated Dextran Sodium Sulfate (DSS)-induced colitis in mice as evidenced by rescue of colon length shortening and lower disease activity index. Overall, this study identifies high calcium amounts as a potential target to lower T cell activation. The implications of these observations are discussed in the context of calcium modulating drugs that are used to treat various diseases.},
}

Animals
*Hydroquinones/pharmacology
*Calcium/metabolism
*Cell Proliferation/drug effects
*T-Lymphocytes/drug effects/immunology/metabolism
Mice
*Lymphocyte Activation/drug effects
*Reactive Oxygen Species/metabolism
Mice, Inbred C57BL
Colitis/drug therapy/chemically induced/immunology
Cells, Cultured
Ionomycin/pharmacology
Dextran Sulfate
NF-E2-Related Factor 2/metabolism/genetics
Tetradecanoylphorbol Acetate/pharmacology
Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism/genetics
Female

@article {pmid39489186,
year = {2024},
author = {Chen, C and Wang, T and Gao, TY and Chen, YL and Lu, YB and Zhang, WP},
title = {Ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and induces Parkinson's disease in mouse.},
journal = {Brain research bulletin},
volume = {218},
number = {},
pages = {111114},
doi = {10.1016/j.brainresbull.2024.111114},
pmid = {39489186},
issn = {1873-2747},
mesh = {Animals ; *Nicotinamide Phosphoribosyltransferase/metabolism ; *Dopaminergic Neurons/metabolism/pathology/drug effects ; Mice ; *Rotenone/toxicity/pharmacology ; Parkinson Disease/metabolism/pathology ; Cytokines/metabolism ; Substantia Nigra/metabolism/pathology/drug effects ; NAD/metabolism ; Reactive Oxygen Species/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; Humans ; Mitochondria/metabolism/drug effects ; Disease Models, Animal ; Male ; Cell Line, Tumor ; },
abstract = {Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the salvaging synthesize pathway of nicotinamide adenine dinucleotide (NAD). The neuroprotective roles of NAMPT on neurodegeneration have been explored in aging brain and Alzheimer's Disease. However, its roles in Parkinson's Disease (PD) remain to be elucidated. We found that the dopaminergic neurons in substantia nigra expressed higher levels of NAMPT than the other types of neurons. Using conditional knockout of the Nampt gene in dopaminergic neurons and utilizing a NAMPT inhibitor in the substantia nigra of mice, we found that the NAMPT deficiency triggered the time-dependent loss of dopaminergic neurons, the impairment of the dopamine nigrostriatal pathway, and the development of PD-like motor dysfunction. In the rotenone-induced PD mouse model, nicotinamide ribose (NR), a precursor of NAD, rescued the loss of dopaminergic neurons, the impairment of dopamine nigrostriatal pathway, and mitigated PD-like motor dysfunction. In SH-SY5Y cells, NAD suppression induced the accumulation of reactive oxygen species (ROS), mitochondrial impairment, and cell death, which was reversed by N-acetyl cysteine, an antioxidant and ROS scavenger. Rotenone decreased NAD level, induced the accumulation of ROS and the impairment of mitochondria, which was reversed by NR. In summary, our findings show that the ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and contributes to the development of PD. The NAD precursors have the potential to protect the degeneration of dopaminergic neurons, and offering a therapeutic approach for the treatment of PD.},
}

Animals
*Nicotinamide Phosphoribosyltransferase/metabolism
*Dopaminergic Neurons/metabolism/pathology/drug effects
Mice
*Rotenone/toxicity/pharmacology
Parkinson Disease/metabolism/pathology
Cytokines/metabolism
Substantia Nigra/metabolism/pathology/drug effects
NAD/metabolism
Reactive Oxygen Species/metabolism
Mice, Knockout
Mice, Inbred C57BL
Humans
Mitochondria/metabolism/drug effects
Disease Models, Animal
Male
Cell Line, Tumor

@article {pmid39489865,
year = {2024},
author = {Har-Zahav, A and Tobar, A and Fried, S and Sivan, R and Wilkins, BJ and Russo, P and Shamir, R and Wells, RG and Gurevich, M and Waisbourd-Zinman, O},
title = {Oral N-acetylcysteine ameliorates liver fibrosis and enhances regenerative responses in Mdr2 knockout mice.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26513},
pmid = {39489865},
issn = {2045-2322},
support = {72-12//PSC Partners Seeking a Cure/ ; 1879/21//The Israeli Science Foundation/ ; },
mesh = {Animals ; Male ; Mice ; *Acetylcysteine/pharmacology/administration & dosage ; Administration, Oral ; *ATP Binding Cassette Transporter, Subfamily B/genetics/metabolism ; *ATP-Binding Cassette Sub-Family B Member 4 ; Disease Models, Animal ; Liver/drug effects/metabolism/pathology ; *Liver Cirrhosis/drug therapy/pathology/metabolism ; Liver Regeneration/drug effects ; Mice, Knockout ; },
abstract = {Cholangiopathies are poorly understood disorders with no effective therapy. The extrahepatic biliary tree phenotype is less studied compared to the intrahepatic biliary injury in both human disease and Mdr2[-/-] mice, the established cholestatic mouse model. This study aimed to characterize the extra hepatic biliary tree of Mdr2[-/-] mice at various ages and to determine if injury can be repaired with the antioxidant and glutathione precursor N-acetyl-L-Cysteine treatment (NAC). We characterized extra hepatic bile ducts (EHBD)s at various ages from 2 to 40 weeks old FVB/N and Mdr2[-/-] mice. We examined the therapeutic potential of local NAC ex vivo using EHBD explants at early and late stages of injury; and systematic therapy by in vivo oral administration for 3 weeks. EHBD and liver sections were assessed by histology and immunofluorescent stains. Serum liver enzyme activities were analyzed, and liver spatial protein expression analysis was performed. Mdr2[-/-] mice developed progressive EHBD injury, similar to extrahepatic PSC. NAC treatment of ex vivo EHBD explants led to improved duct morphology. In vivo, oral administration of NAC improved liver fibrosis, and decreased liver enzyme activities. Spatial protein analysis revealed cell-type specific differential response to NAC, collectively indicating a transition from pro-apoptotic into proliferative state. NAC treatment should be further investigated as a potential therapeutic option for human cholangiopathies.},
}

Animals
Male
Mice
*Acetylcysteine/pharmacology/administration & dosage
Administration, Oral
*ATP Binding Cassette Transporter, Subfamily B/genetics/metabolism
*ATP-Binding Cassette Sub-Family B Member 4
Disease Models, Animal
Liver/drug effects/metabolism/pathology
*Liver Cirrhosis/drug therapy/pathology/metabolism
Liver Regeneration/drug effects
Mice, Knockout

@article {pmid39490995,
year = {2024},
author = {Zhao, E and Liang, R and Li, P and Lu, D and Chen, S and Tan, W and Qin, Y and Zhang, Y and Zhang, Y and Zhang, Q and Liu, Q},
title = {Mesenchymal stromal cells alleviate APAP-induced liver injury via extracellular vesicle-mediated regulation of the miR-186-5p/CXCL1 axis.},
journal = {Stem cell research & therapy},
volume = {15},
number = {1},
pages = {392},
pmid = {39490995},
issn = {1757-6512},
support = {81971526 and 82370629//the National Natural Science Foundation of China/ ; 2022A1515012223//the Natural Science Foundation of Guangdong Province/ ; 202201020398, 202201020430//the Science and Technology Program of Guangzhou/ ; },
mesh = {*Mesenchymal Stem Cells/metabolism/cytology ; *MicroRNAs/metabolism/genetics ; *Chemokine CXCL1/metabolism/genetics ; *Extracellular Vesicles/metabolism ; Animals ; *Chemical and Drug Induced Liver Injury/metabolism/therapy ; Mice ; *Acetaminophen/adverse effects ; Humans ; Male ; Mice, Inbred C57BL ; Mesenchymal Stem Cell Transplantation/methods ; },
abstract = {BACKGROUND: Acetaminophen (APAP) overdose is a significant cause of drug-induced liver injury (DILI). N-acetylcysteine (NAC) is the first-line agent used in the clinic. However, it rarely benefits patients with advanced APAP toxicity. Mesenchymal stromal cells (MSCs) have demonstrated potential in treating DILI. However, the specific mechanism by which MSCs protect against APAP-induced liver injury remains unclear.

METHODS: APAP was injected intraperitoneally to induce a liver injury model. We then detected histopathology, biochemical indices, and inflammatory cytokine levels to assess the efficacy of MSCs and MSC extracellular vesicles (MSC-EVs). Flow cytometry was performed to reveal the immunoregulatory effects of MSCs and MSC-EVs on the neutrophils. RNA sequencing (RNA-Seq) of liver tissues was used to identify critical target genes for MSC treatment.

RESULTS: MSC and MSC-EV treatment effectively alleviated APAP-induced liver injury and inhibited neutrophil infiltration. RNA-Seq analysis and ELISA data indicated that C-X-C motif chemokine 1 (CXCL1), a chemoattractant for neutrophils, was a key molecule in the MSC-mediated amelioration of APAP-induced liver damage. In addition, neutralization of CXCL1 reduced APAP-induced liver damage, which was accompanied by decreased neutrophil infiltration. Importantly, we verified that MSC-EV-derived miR-186-5p directly binds to the 3'-UTR of Cxcl1 to inhibit its expression in hepatocytes. The agomir miR-186-5p showed excellent potential for the treatment of DILI.

CONCLUSIONS: Our findings suggest that MSCs and MSC-EVs are an effective approach to mitigate DILI. Targeting the miR-186-5p/CXCL1 axis is a promising approach to improve the efficacy of MSCs and MSC-EVs in the treatment of DILI.},
}

*Mesenchymal Stem Cells/metabolism/cytology
*MicroRNAs/metabolism/genetics
*Chemokine CXCL1/metabolism/genetics
*Extracellular Vesicles/metabolism
Animals
*Chemical and Drug Induced Liver Injury/metabolism/therapy
Mice
*Acetaminophen/adverse effects
Humans
Male
Mice, Inbred C57BL
Mesenchymal Stem Cell Transplantation/methods

@article {pmid39492659,
year = {2025},
author = {Angelini, A and Garcia Marquez, G and Malovannaya, A and Fiorotto, ML and Saltzman, A and Jain, A and Trial, J and Taffet, GE and Cieslik, KA},
title = {Sex Differences in Response to Diet Enriched With Glutathione Precursors in the Aging Heart.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {80},
number = {2},
pages = {},
pmid = {39492659},
issn = {1758-535X},
support = {3R01AG059599-03S1//Office of Dietary Supplements/ ; S10 OD026804/OD/NIH HHS/United States ; R01 AG059599/AG/NIA NIH HHS/United States ; //BCM Mass Spectrometry Proteomics Core/ ; P30 CA125123/CA/NCI NIH HHS/United States ; //Hankamer Foundation/ ; R01 AG080925/AG/NIA NIH HHS/United States ; RP210227//CPRIT Core Facility/ ; 1R01AG080925/AG/NIA NIH HHS/United States ; S10 OD026804/CD/ODCDC CDC HHS/United States ; },
mesh = {Animals ; Male ; Female ; *Aging/physiology ; Mice ; *Glutathione/metabolism ; *Glycine/pharmacology/administration & dosage ; Mice, Inbred C57BL ; *Heart/physiology/drug effects ; *Acetylcysteine/pharmacology/administration & dosage ; Sex Factors ; Myocardium/metabolism ; Oxidative Stress/drug effects ; Dietary Supplements ; Diet ; Sex Characteristics ; Antioxidants ; },
abstract = {Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a subunit of the mitochondrial respiratory chain complex), and higher enzymatic activity for CPT1b and CrAT, 2 carnitine acyltransferases that are critical to cardiomyocyte metabolism. Although no quantifiable change of collagen turnover was detected, hearts from GlyNAC-fed old males exhibited a slight but significant enrichment in Fmod, a protein that can inhibit collagen fibril formation, possibly reducing extracellular matrix stiffness and thus improving diastolic function. Cardiac diastolic function was modestly improved in males but not females, and surprisingly GlyNAC-fed female mice showed a decline in exercise performance. In summary, our work supports the concept that aged male and female hearts are phenotypically different. These basic differences may affect the response to pharmacological and diet interventions, including antioxidants.},
}

Animals
Male
Female
*Aging/physiology
Mice
*Glutathione/metabolism
*Glycine/pharmacology/administration & dosage
Mice, Inbred C57BL
*Heart/physiology/drug effects
*Acetylcysteine/pharmacology/administration & dosage
Sex Factors
Myocardium/metabolism
Oxidative Stress/drug effects
Dietary Supplements
Diet
Sex Characteristics
Antioxidants

@article {pmid39493346,
year = {2024},
author = {Pastore, A and Badolati, N and Manfrevola, F and Sagliocchi, S and Laurenzi, V and Musto, G and Porreca, V and Murolo, M and Chioccarelli, T and Ciampaglia, R and Vellecco, V and Bucci, M and Dentice, M and Cobellis, G and Stornaiuolo, M},
title = {N-acetyl-L-cysteine reduces testis ROS in obese fathers but fails in protecting offspring from acquisition of epigenetic traits at cyp19a1 and IGF11/H19 ICR loci.},
journal = {Frontiers in cell and developmental biology},
volume = {12},
number = {},
pages = {1450580},
pmid = {39493346},
issn = {2296-634X},
abstract = {INTRODUCTION: Paternal nutrition before conception has a marked impact on offspring's risk of developing metabolic disorders during adulthood. Research on human cohorts and animal models has shown that paternal obesity alters sperm epigenetics (DNA methylation, protamine-to-histone replacement, and non-coding RNA content), leading to adverse health outcomes in the offspring. So far, the mechanistic events that translate paternal nutrition into sperm epigenetic changes remain unclear. High-fat diet (HFD)-driven paternal obesity increases gonadic Reactive Oxygen Species (ROS), which modulate enzymes involved in epigenetic modifications of DNA during spermatogenesis. Thus, the gonadic pool of ROS might be responsible for transducing paternal health status to the zygote through germ cells.

METHODS: The involvement of ROS in paternal intergenerational transmission was assessed by modulating the gonadic ROS content in male mice. Testicular oxidative stress induced by HFD was counterbalanced by N-acetylcysteine (NAC), an antioxidant precursor of GSH. The sires were divided into four feeding groups: i) control diet; ii) HFD; iii) control diet in the presence of NAC; and iv) HFD in the presence of NAC. After 8 weeks, males were mated with females that were fed a control diet. Antioxidant treatment was then evaluated in terms of preventing the HFD-induced transmission of dysmetabolic traits from obese fathers to their offspring. The offspring were weaned onto a regular control diet until week 16 and then underwent metabolic evaluation. The methylation status of the genomic region IGFII/H19 and cyp19a1 in the offspring gDNA was also assessed using Sanger sequencing and methylation-dependent qPCR.

RESULTS: Supplementation with NAC protected sires from HFD-induced weight gain, hyperinsulinemia, and glucose intolerance. NAC reduced oxidative stress in the gonads of obese fathers and improved sperm viability. However, NAC did not prevent the transmission of epigenetic modifications from father to offspring. Male offspring of HFD-fed fathers, regardless of NAC treatment, exhibited hyperinsulinemia, glucose intolerance, and hypoandrogenism. Additionally, they showed altered methylation at the epigenetically controlled loci IGFII/H19 and cy19a1.

CONCLUSION: Although NAC supplementation improved the health status and sperm quality of HFD-fed male mice, it did not prevent the epigenetic transmission of metabolic disorders to their offspring. Different NAC dosages and antioxidants other than NAC might represent alternatives to stop the intergenerational transmission of paternal dysmetabolic traits.},
}

@article {pmid39493366,
year = {2024},
author = {Rogliani, P and Manzetti, GM and Gholamalishahi, S and Cazzola, M and Calzetta, L},
title = {Impact of N-Acetylcysteine on Mucus Hypersecretion in the Airways: A Systematic Review.},
journal = {International journal of chronic obstructive pulmonary disease},
volume = {19},
number = {},
pages = {2347-2360},
pmid = {39493366},
issn = {1178-2005},
mesh = {Animals ; Humans ; *Acetylcysteine/pharmacology/therapeutic use ; *Expectorants/pharmacology/therapeutic use ; *Goblet Cells/drug effects/metabolism ; Hyperplasia ; *Lung/drug effects/metabolism ; Mucin 5AC/metabolism/genetics ; Mucin-5B/metabolism/genetics ; Mucociliary Clearance/drug effects ; *Mucus/metabolism ; *Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism/physiopathology ; },
abstract = {Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear. This systematic review evaluated the impact of NAC on MHS in the airways, reporting significant inhibitory effects on MUC5AC and MUC5B gene and protein expression, as well as a reduction in the number of goblet cells. NAC has demonstrated efficacy in vitro and in animal models of MHS, including COPD models, but data on human bronchial tissue are lacking. This systematic review suggests that NAC acts as a mucolytic and a mucoregulator, directly inhibiting mucus secretion and goblet cell hyperplasia. Given the critical role of MHS in COPD progression, exacerbations, and mortality, these findings highlight the potential of NAC as a targeted therapy for hypersecretion COPD phenotypes. However, further studies are needed to confirm the results of this systematic review, even in human bronchial tissue, to provide translatable evidence in clinical settings. Understanding the intimate mechanism of NAC versus MHS regulation may pave the way for more effective treatments targeting airway mucus dysfunction in COPD, ultimately improving patient outcomes and reducing morbidity and mortality associated with chronic mucus hypersecretion.},
}

Animals
Humans
*Acetylcysteine/pharmacology/therapeutic use
*Expectorants/pharmacology/therapeutic use
*Goblet Cells/drug effects/metabolism
Hyperplasia
*Lung/drug effects/metabolism
Mucin 5AC/metabolism/genetics
Mucin-5B/metabolism/genetics
Mucociliary Clearance/drug effects
*Mucus/metabolism
*Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism/physiopathology

@article {pmid39493971,
year = {2024},
author = {Xu, C and Chen, Y and Zhou, Z and Yan, Y and Fu, W and Zou, P and Ni, D},
title = {ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells.},
journal = {ACS omega},
volume = {9},
number = {43},
pages = {43697-43705},
pmid = {39493971},
issn = {2470-1343},
abstract = {Lung cancer is one of the leading causes of death. Celastrol is a natural product that has shown anticancer activity but has not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol. At the same time, celastrol upregulated the expression of cytoprotective transcription factor Nrf2 and its downstream proteins, which are effective in preventing the oxidative damage caused by ROS accumulation. Notably, we found that the overexpression of Nrf2 enhances the tolerance of lung cancer cells to celastrol and that lung cancer cells H460 with a Keap1 mutation are insensitive to celastrol. This indicates that the increase in Nrf2 contributes to the survival of lung cancer cells. Thus, we brought in an Nrf2 inhibitor ML385 to suppress the activation of Nrf2. We found that when ML385 and celastrol were added together the survival rates of lung cancer cells decreased more and the detected ROS level became much higher compared to treatment with celastrol alone. We also discovered that ML385 suppressed the expression of HO-1 and GCLC, which amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.},
}

@article {pmid39494328,
year = {2024},
author = {Kim, HB and Kim, YJ and Lee, YJ and Yoo, JY and Choi, Y and Kim, EM and Suh, SW and Woo, RS},
title = {N-Acetylcysteine Alleviates Depressive-Like Behaviors in Adolescent EAAC1[-/-] Mice and Early Life Stress Model Rats.},
journal = {International journal of biological sciences},
volume = {20},
number = {14},
pages = {5450-5473},
pmid = {39494328},
issn = {1449-2288},
mesh = {Animals ; *Acetylcysteine/therapeutic use/pharmacology ; Male ; Female ; Mice ; *Depression/drug therapy/metabolism ; Rats ; *Excitatory Amino Acid Transporter 3/metabolism ; *Stress, Psychological/drug therapy ; Hippocampus/metabolism/drug effects ; Oxidative Stress/drug effects ; Mice, Knockout ; Disease Models, Animal ; Rats, Sprague-Dawley ; Behavior, Animal/drug effects ; Maternal Deprivation ; },
abstract = {Exposure to adverse experiences during early life is associated with an increased risk of psychopathology during adolescence. In a previous study, we demonstrated that neonatal maternal separation (NMS) combined with social isolation led to impulsive and depressive-like behaviors in male adolescents. Additionally, it significantly reduced the expression of excitatory amino acid carrier 1 (EAAC1) in the hippocampus. Building upon this work, we investigated the effects of N-acetylcysteine (NAC), a precursor to glutathione, in early-life stress (ELS) model rats and in EAAC1[-/-] mice. EAAC1 plays a dual role in transporting both glutamate and cysteine into neurons. Our findings revealed that female adolescents subjected to in the ELS model also exhibited behavioral defects similar to those of males. NAC injection rescued depressive-like behaviors in both male and female NMS models, but it improved impulsive behavior only in males. Furthermore, we observed increased reactive oxidative stress (ROS) and neuroinflammation in the ventral hippocampus (vHPC) and prefrontal cortex of NMS model rats, which were mitigated by NAC treatment. Notably, NAC reversed the reduced expression of EAAC1 in the vHPC of NMS model rats. In EAAC1[-/-] mice, severe impulsive and depressive-like behaviors were evident, and the NAC intervention improved only depressive-like behaviors. Collectively, our results suggest that ELS contributes to depression and impulsive behaviors during adolescence. Moreover, the cysteine uptake function of EAAC1 in neurons may be specifically related to depression rather than impulsive behavior.},
}

Animals
*Acetylcysteine/therapeutic use/pharmacology
Male
Female
Mice
*Depression/drug therapy/metabolism
Rats
*Excitatory Amino Acid Transporter 3/metabolism
*Stress, Psychological/drug therapy
Hippocampus/metabolism/drug effects
Oxidative Stress/drug effects
Mice, Knockout
Disease Models, Animal
Rats, Sprague-Dawley
Behavior, Animal/drug effects
Maternal Deprivation