@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 {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},
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.},
}

@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},
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.},
}

@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 {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 = {},
doi = {10.3390/ani14192852},
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 {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 = {},
doi = {10.3390/ijms251910858},
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 {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 {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},
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.},
}

@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 {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 = {},
number = {},
pages = {123128},
doi = {10.1016/j.lfs.2024.123128},
pmid = {39393575},
issn = {1879-0631},
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 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.},
}

@article {pmid39389326,
year = {2024},
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 = {},
number = {},
pages = {148992},
doi = {10.1016/j.gene.2024.148992},
pmid = {39389326},
issn = {1879-0038},
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.},
}

@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 = {},
number = {},
pages = {123109},
doi = {10.1016/j.lfs.2024.123109},
pmid = {39384146},
issn = {1879-0631},
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.},
}

@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 {pmid38962807,
year = {2024},
author = {Lv, H and Yang, H and Duan, Y and Yan, C and Li, G and Zhao, G and Sun, F and Feng, Y and Li, Y and Fu, Y and Li, Y and Zhao, Z and Jia, X},
title = {S-(N,N-diethyldithiocarbamoyl)-N-acetyl-l-cysteine for the treatment of non-small cell lung cancer through regulating NF-κB signalling pathway without neurotoxicity.},
journal = {Journal of drug targeting},
volume = {32},
number = {9},
pages = {1111-1124},
doi = {10.1080/1061186X.2024.2374037},
pmid = {38962807},
issn = {1029-2330},
mesh = {Animals ; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology ; *NF-kappa B/metabolism ; Humans ; Mice ; *Lung Neoplasms/drug therapy/pathology ; *Signal Transduction/drug effects ; Cell Line, Tumor ; *Antineoplastic Agents/pharmacology/administration & dosage ; Acetylcysteine/pharmacology ; Cell Proliferation/drug effects ; Apoptosis/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; A549 Cells ; Mice, Nude ; Xenograft Model Antitumor Assays ; Ditiocarb/pharmacology ; Mice, Inbred BALB C ; },
abstract = {The discovery of novel targeted agents for non-small cell lung cancer (NSCLC) remains an important research landscape due to the limited efficacy, side effects and drug resistance of current treatment options. Among many repurposed drugs, disulphiram (DSF) has shown the potential to target tumours. However, its unpleasant neurotoxicity greatly limits its use. A DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-l-cysteine (DS-NAC), was synthesised against NSCLC. The therapeutic effects, mechanism and toxicities of DS-NAC were evaluated in A549 and H460 cells and the mouse model of in situ lung cancer. The in vitro results exhibited that DS-NAC had potent anti-proliferation, apoptotic, anti-metastasis and epithelial-mesenchymal transition (EMT) inhibition effects. In the orthotopic lung cancer mouse model, therapeutic effects of DS-NAC were better than those of DSF and were similar to docetaxel (DTX). Also, results from western blot and immunohistochemistry showed that DS-NAC in combination with copper exerted therapeutic effects via regulating NF-κB signalling pathway and ROS-related proteins such as HIF-1α, Nrf2 and PKC-δ rather than regulating ROS level directly. Moreover, the safety evaluation study showed that DS-NAC had low haematologic and hepatic toxicities in comparison with DTX as well as low neurological toxicity compared with DSF. DS-NAC could be a promising anti-lung cancer agent with a favourable safety profile.},
}

Animals
*Carcinoma, Non-Small-Cell Lung/drug therapy/pathology
*NF-kappa B/metabolism
Humans
Mice
*Lung Neoplasms/drug therapy/pathology
*Signal Transduction/drug effects
Cell Line, Tumor
*Antineoplastic Agents/pharmacology/administration & dosage
Acetylcysteine/pharmacology
Cell Proliferation/drug effects
Apoptosis/drug effects
Epithelial-Mesenchymal Transition/drug effects
A549 Cells
Mice, Nude
Xenograft Model Antitumor Assays
Ditiocarb/pharmacology
Mice, Inbred BALB C

@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 {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 {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 {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 = {},
number = {},
pages = {123104},
doi = {10.1016/j.lfs.2024.123104},
pmid = {39366552},
issn = {1879-0631},
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 averted and 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.},
}

@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 {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},
doi = {10.4103/aca.aca_156_24},
pmid = {39365126},
issn = {0974-5181},
mesh = {Humans ; *Cardiopulmonary Bypass/adverse effects ; *Acetylcysteine/therapeutic use ; Liver Diseases ; Liver Function Tests ; Liver/drug effects ; Male ; Female ; },
}

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

@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 = {},
number = {},
pages = {e6012},
doi = {10.1002/bmc.6012},
pmid = {39363690},
issn = {1099-0801},
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.},
}

@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 = {},
number = {},
pages = {},
doi = {10.55563/clinexprheumatol/dmd5dv},
pmid = {39360368},
issn = {0392-856X},
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.},
}

@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 = {},
number = {},
pages = {},
doi = {10.1016/j.burns.2024.09.012},
pmid = {39353794},
issn = {1879-1409},
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.},
}

@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 {pmid39357253,
year = {2024},
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},
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.},
}

@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 {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 {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},
doi = {10.1371/journal.pone.0307212},
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 {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 = {},
doi = {10.3390/v16091503},
pmid = {39339978},
issn = {1999-4915},
mesh = {*Peptide Elongation Factor 1/metabolism/genetics ; *Virus Replication/drug effects ; *Enterovirus B, Human/drug effects/physiology ; Animals ; *Acetylcysteine/pharmacology ; Humans ; Mice ; *Coxsackievirus Infections/drug therapy/virology ; *Down-Regulation/drug effects ; Antiviral Agents/pharmacology ; Cell Line ; Myocarditis/virology/drug therapy ; Male ; },
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.},
}

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

@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 = {},
doi = {10.3390/pharmaceutics16091123},
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 {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 = {},
doi = {10.3390/ijms251810198},
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 {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 = {},
doi = {10.3390/ijms25189986},
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 {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 = {},
doi = {10.3390/ijms25189857},
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 {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 = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2024.09.042},
pmid = {39332540},
issn = {1873-4596},
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.},
}

@article {pmid39331828,
year = {2024},
author = {Moraes, LGDS and Oliveira, VC and Macedo, AP and Freiria de Oliveira, CA and Watanabe, E and Pagnano, VO},
title = {Enhancing Removable Partial Dentures Hygiene: Investigating Mucolytic Agents and Biocides for Disrupting Biofilms and Improving Antimicrobial Efficacy.},
journal = {The International journal of prosthodontics},
volume = {0},
number = {0},
pages = {1-25},
doi = {10.11607/ijp.9133},
pmid = {39331828},
issn = {1942-4426},
abstract = {PURPOSE: This study evaluates 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 cobaltchromium (Co-Cr) alloy.

MATERIALS AND METHODS: A multispecies biofilm was grown on the surface of AR and Co-Cr specimens (Ø 12×3mm). 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 the Tukey post-test or Kruskal-Wallis followed by the Dunn post-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 distinct effect according to the surface, being most effective in reducing CFU on AR than the Co-Cr surface. However, it did not influence XTT, and 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.},
}

@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 {pmid39313073,
year = {2024},
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 = {},
number = {},
pages = {115261},
doi = {10.1016/j.bbr.2024.115261},
pmid = {39313073},
issn = {1872-7549},
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 to 51. Rats were trained to self-administer intravenous amphetamine (0.1mg/kg/infusion) during twelve 6-hour sessions. During the abstinence period, NAC (100mg/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.},
}

@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 {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 {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 {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 = {},
number = {},
pages = {},
doi = {10.3233/JAD-240709},
pmid = {39302378},
issn = {1875-8908},
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.},
}

@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 = {},
doi = {10.3892/mmr.2024.13330},
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 {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 = {},
number = {},
pages = {107340},
doi = {10.1016/j.ijantimicag.2024.107340},
pmid = {39299599},
issn = {1872-7913},
abstract = {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. 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. 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. 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. 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.},
}

@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},
doi = {10.1192/bjo.2024.740},
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 {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 = {},
doi = {10.21203/rs.3.rs-4947457/v1},
pmid = {39281865},
issn = {2693-5015},
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 (x c [-]) 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 {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 = {},
number = {},
pages = {110096},
doi = {10.1016/j.exer.2024.110096},
pmid = {39278392},
issn = {1096-0007},
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.},
}

@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},
doi = {10.12122/j.issn.1673-4254.2024.08.14},
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 {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 {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 = {},
doi = {10.3390/cancers16173108},
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 {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 {pmid39265983,
year = {2024},
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 = {},
number = {},
pages = {1-19},
doi = {10.1080/15548627.2024.2395142},
pmid = {39265983},
issn = {1554-8635},
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.},
}

@article {pmid39265812,
year = {2024},
author = {Pazarci, Ö and Hümeyra Taşkin Kafa, A and Taş, A and Keklikçioğlu 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 = {},
number = {},
pages = {106934},
doi = {10.1016/j.micpath.2024.106934},
pmid = {39265812},
issn = {1096-1208},
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 250-500 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 hours. 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.},
}

@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},
doi = {10.21037/cdt-24-19},
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 {pmid39262205,
year = {2024},
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 = {},
number = {},
pages = {8850666241281281},
doi = {10.1177/08850666241281281},
pmid = {39262205},
issn = {1525-1489},
abstract = {PURPOSE: We assessed the potential association between N-acetyl-cysteine (NAC) and clinical outcomes in critically ill subjects with COVID-19-related ARDS.

MATERIAL AND METHODS: We 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.

RESULTS: A 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).

CONCLUSIONS: We found that oral administration of NAC was associated with reduced mortality in critically ill patients with COVID-19 related ARDS.},
}

@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 = {},
number = {},
pages = {124922},
doi = {10.1016/j.envpol.2024.124922},
pmid = {39260547},
issn = {1873-6424},
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 livers 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-acetyl-cysteine (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.},
}

@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 = {},
number = {},
pages = {1-10},
doi = {10.1080/10715762.2024.2396909},
pmid = {39258904},
issn = {1029-2470},
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.},
}

@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},
doi = {10.1016/j.bpsgos.2024.100361},
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 {pmid39182400,
year = {2025},
author = {Feng, Y and Yuan, J and Yang, X and Ma, X and Cheng, Z},
title = {Developing an off-on fluorescence sensor based on red copper nanoclusters wrapped by sulfhydryl and polymer double ligands for sensitive detection of N-acetyl-L-cysteine.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {324},
number = {},
pages = {125008},
doi = {10.1016/j.saa.2024.125008},
pmid = {39182400},
issn = {1873-3557},
mesh = {*Acetylcysteine/chemistry/urine ; *Copper/chemistry/analysis ; *Spectrometry, Fluorescence/methods ; *Sulfhydryl Compounds/chemistry/analysis ; Ligands ; *Metal Nanoparticles/chemistry ; *Limit of Detection ; Mercury/analysis/urine ; Humans ; Fluorescent Dyes/chemistry ; Povidone/chemistry ; Benzoates/chemistry ; Polymers/chemistry ; },
abstract = {N-acetyl-L-cysteine (NAC) as a class of thiols is commonly used in the treatment of lung diseases, detoxification and prevention of liver damage. In this paper, 4-mercaptobenzoic acid (4-MBA) coated and polyvinylpyrrolidone (PVP) attached copper nanoclusters (4-MBA@PVP-CuNCs) were successfully synthesized using a simple one-pot method with an absolute quantum yield of 10.98 %, and its synthetic conditions (like effects of single/double ligands and temperature) were studied intensively. Then Hg[2+] could quench the fluorescence of the 4-MBA@PVP-CuNCs and its fluorescence was restored with the addition of NAC. Based on the above principles, an off-on switching system was established to detect NAC. That is, the 4-MBA@PVP-CuNCs-Hg probe was prepared by adding Hg[2+] to switch off the fluorescence of the CuNCs by static quenching, and then NAC was added to switch on the fluorescence of the probe based on the chelation of NAC and Hg[2+]. Moreover, the effects of metal ion types and mercury ion doses for the probe construction were also further discussed. The method showed excellent linearity in the range of 0.05-1.25 µM and low detection limit of 16 nM. Meanwhile, good recoveries in real urine, tablets and pellets were observed, which proved the reliability of the method and provided a convenient, fast and sensitive method for NAC detection.},
}

*Acetylcysteine/chemistry/urine
*Copper/chemistry/analysis
*Spectrometry, Fluorescence/methods
*Sulfhydryl Compounds/chemistry/analysis
Ligands
*Metal Nanoparticles/chemistry
*Limit of Detection
Mercury/analysis/urine
Humans
Fluorescent Dyes/chemistry
Povidone/chemistry
Benzoates/chemistry
Polymers/chemistry

@article {pmid39180519,
year = {2024},
author = {Yang, H and Liu, Y and Wang, C and Hussain, M and Ettayri, K and Chen, Y and Wang, K and Long, L and Qian, J},
title = {Ultrastable NAC-Capped CdZnTe Quantum Dots Encapsulated within Dendritic Mesoporous Silica As an Exceptional Tag for Anti-Interference Fluorescence Aptasensor with Signal Amplification.},
journal = {Analytical chemistry},
volume = {96},
number = {36},
pages = {14550-14559},
doi = {10.1021/acs.analchem.4c02826},
pmid = {39180519},
issn = {1520-6882},
mesh = {*Quantum Dots/chemistry ; *Silicon Dioxide/chemistry ; *Tellurium/chemistry ; *Cadmium Compounds/chemistry ; *Biosensing Techniques/methods ; *Aptamers, Nucleotide/chemistry ; Porosity ; Acetylcysteine/chemistry ; Fluorescence ; Spectrometry, Fluorescence ; Limit of Detection ; Cadmium ; Zinc ; },
abstract = {In this work, we explored the potential of thiol-capped CdZnTe quantum dots (QDs) as an exceptional signal tag for fluorescence aptasensing applications. Employing a one-pot hydrothermal approach, we modulated the terminal functional groups of CdZnTe QDs using l-cysteine (Lcys), 3-mercaptopropionic acid (MPA), and N-acetyl-l-cysteine (NAC) as ligands. Our comparative analysis revealed that NAC-capped CdZnTe QDs (NAC-CdZnTe QDs) exhibited superior anti-interference capabilities and storage stability across various temperatures, pH levels, and storage durations. Encouraged by these promising results, we further optimized the use of ultrastable NAC-CdZnTe QDs encapsulated in dendritic mesoporous silica nanoparticles (DMSN@QDs) as an exceptional tag for the development of an advanced anti-interference fluorescence aptasensor for aflatoxin B1 (AFB1) detection. The developed aptasensor using DMSN@QDs as signal tags achieved a remarkable signal amplification of approximately 10.2 fold compared to the NAC-CdZnTe QDs coated silica (SiO2@QDs) labeled fluorescence aptasensor. This aptasensor was able to detect AFB1 within a wide range of 1 pg mL[-1] to 200 ng mL[-1], achieving a limit of detection as low as 0.41 pg mL[-1] (S/N = 3). Crucially, the specific binding affinity between the aptamer and the target enabled the aptasensor to be easily customized for various targets by simply replacing the aptamer sequence with the desired one. The exceptional potential of NAC-CdZnTe QDs, particularly when encapsulated in DMSNs, leads to the development of highly sensitive and selective anti-interference fluorescence aptasensors for various targets, thereby, paving the way for advancements in a diverse range of applications.},
}

*Quantum Dots/chemistry
*Silicon Dioxide/chemistry
*Tellurium/chemistry
*Cadmium Compounds/chemistry
*Biosensing Techniques/methods
*Aptamers, Nucleotide/chemistry
Porosity
Acetylcysteine/chemistry
Fluorescence
Spectrometry, Fluorescence
Limit of Detection
Cadmium
Zinc

@article {pmid39251120,
year = {2024},
author = {Wood, JPM and Chidlow, G and Wall, GM and Casson Franzco, RJ},
title = {N-ACETYLCYSTEINE AMIDE AND DI- N-ACETYLCYSTEINE AMIDE PROTECT RETINAL CELLS IN CULTURE VIA AN ANTIOXIDANT ACTION.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110074},
doi = {10.1016/j.exer.2024.110074},
pmid = {39251120},
issn = {1096-0007},
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.},
}

@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 = {},
number = {},
pages = {114988},
doi = {10.1016/j.fct.2024.114988},
pmid = {39251036},
issn = {1873-6351},
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 to 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.},
}

@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 = {},
number = {},
pages = {},
doi = {10.1002/em.22627},
pmid = {39248027},
issn = {1098-2280},
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.},
}

@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 {pmid39245438,
year = {2024},
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 = {},
number = {},
pages = {1-20},
doi = {10.1080/15548627.2024.2395799},
pmid = {39245438},
issn = {1554-8635},
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.},
}

@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 = {},
number = {},
pages = {135418},
doi = {10.1016/j.ijbiomac.2024.135418},
pmid = {39245103},
issn = {1879-0003},
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.},
}

@article {pmid39239906,
year = {2024},
author = {Guo, J and Xu, Q and Zhong, Y and Su, Y},
title = {acetylcysteine promotes doxycycline resistance in the bacterial pathogen edwardsiella tarda.},
journal = {Virulence},
volume = {},
number = {},
pages = {2399983},
doi = {10.1080/21505594.2024.2399983},
pmid = {39239906},
issn = {2150-5608},
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.},
}

@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 {pmid39225404,
year = {2024},
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 = {},
number = {},
pages = {},
doi = {10.1002/biof.2117},
pmid = {39225404},
issn = {1872-8081},
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.},
}

@article {pmid39223526,
year = {2024},
author = {Rhee, CK and Lim, SY and Lee, WY and Jung, JY and Park, YB and Lee, CY and Hwang, YI and Song, JW and Choi, WI and Yoo, KH and Kim, KU and Kim, YI and Kim, TH and Park, SJ and Shin, KC and Um, SJ and Yoon, HK and Lee, HS and Kim, DK and Leem, AY and , },
title = {The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.},
journal = {BMC pulmonary medicine},
volume = {24},
number = {1},
pages = {434},
pmid = {39223526},
issn = {1471-2466},
mesh = {Humans ; *Acetylcysteine/administration & dosage ; *Pulmonary Disease, Chronic Obstructive/drug therapy/physiopathology ; Male ; Female ; Aged ; Prospective Studies ; *Nebulizers and Vaporizers ; Middle Aged ; Forced Expiratory Volume/drug effects ; Administration, Inhalation ; Vital Capacity/drug effects ; Expectorants/administration & dosage/adverse effects ; Treatment Outcome ; },
abstract = {BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients.

METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score.

RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported.

CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.},
}

Humans
*Acetylcysteine/administration & dosage
*Pulmonary Disease, Chronic Obstructive/drug therapy/physiopathology
Male
Female
Aged
Prospective Studies
*Nebulizers and Vaporizers
Middle Aged
Forced Expiratory Volume/drug effects
Administration, Inhalation
Vital Capacity/drug effects
Expectorants/administration & dosage/adverse effects
Treatment Outcome

@article {pmid39214451,
year = {2024},
author = {Kim, JE and Lee, DS and Wang, SH and Kim, TH and Kang, TC},
title = {GPx1-ERK1/2-CREB pathway regulates the distinct vulnerability of hippocampal neurons to oxidative stress via modulating mitochondrial dynamics following status epilepticus.},
journal = {Neuropharmacology},
volume = {260},
number = {},
pages = {110135},
doi = {10.1016/j.neuropharm.2024.110135},
pmid = {39214451},
issn = {1873-7064},
abstract = {Glutathione peroxidase-1 (GPx1) and cAMP/Ca[2+] responsive element (CRE)-binding protein (CREB) regulate neuronal viability by maintaining the redox homeostasis. Since GPx1 and CREB reciprocally regulate each other, it is likely that GPx1-CREB interaction may play a neuroprotective role against oxidative stress, which are largely unknown. Thus, we investigated the underlying mechanisms of the reciprocal regulation between GPx1 and CREB in the male rat hippocampus. Under physiological condition, L-buthionine sulfoximine (BSO)-induced oxidative stress increased GPx1 expression, extracellular signal-regulated kinase 1/2 (ERK1/2) activity and CREB serine (S) 133 phosphorylation in CA1 neurons, but not dentate granule cells (DGC), which were diminished by GPx1 siRNA, U0126 or CREB knockdown. GPx1 knockdown inhibited ERK1/2 and CREB activations induced by BSO. CREB knockdown also decreased the efficacy of BSO on ERK1/2 activation. BSO facilitated dynamin-related protein 1 (DRP1)-mediated mitochondrial fission in CA1 neurons, which abrogated by GPx1 knockdown and U0126. CREB knockdown blunted BSO-induced DRP1 upregulation without affecting DRP1 S616 phosphorylation ratio. Following status epilepticus (SE), GPx1 expression was reduced in CA1 neurons and DGC. SE also decreased CREB activity CA1 neurons, but not DGC. SE degenerated CA1 neurons, but not DGC, accompanied by mitochondrial elongation. These post-SE events were ameliorated by N-acetylcysteine (NAC, an antioxidant), but deteriorated by GPx1 knockdown. These findings indicate that a transient GPx1-ERK1/2-CREB activation may be a defense mechanism to protect hippocampal neurons against oxidative stress via maintenance of proper mitochondrial dynamics.},
}

@article {pmid39208656,
year = {2024},
author = {Xue, A and Zhang, H and Song, S and Yu, X},
title = {Effects of N-Acetylcysteine combined with Ambroxol Hydrochloride on clinical symptoms, CRP, and PCT in children with pneumonia.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {79},
number = {},
pages = {100476},
doi = {10.1016/j.clinsp.2024.100476},
pmid = {39208656},
issn = {1980-5322},
mesh = {Humans ; *Ambroxol/therapeutic use/administration & dosage ; *C-Reactive Protein/analysis ; *Acetylcysteine/therapeutic use ; Female ; Male ; *Procalcitonin/blood ; Child, Preschool ; *Expectorants/therapeutic use/adverse effects ; *Drug Therapy, Combination ; *Pneumonia/drug therapy ; Child ; Treatment Outcome ; Infant ; Blood Gas Analysis ; },
abstract = {OBJECTIVE: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia.

METHODS: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed.

RESULTS: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05).

CONCLUSION: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.},
}

Humans
*Ambroxol/therapeutic use/administration & dosage
*C-Reactive Protein/analysis
*Acetylcysteine/therapeutic use
Female
Male
*Procalcitonin/blood
Child, Preschool
*Expectorants/therapeutic use/adverse effects
*Drug Therapy, Combination
*Pneumonia/drug therapy
Child
Treatment Outcome
Infant
Blood Gas Analysis

@article {pmid39208572,
year = {2024},
author = {Chen, C and Chen, Y and Zhai, H and Xiao, Y and Xu, J and Gu, Y and Han, X and Wang, C and Chen, Q and Lu, H},
title = {Cadmium exposure induces skeletal muscle insulin resistance through the reactive oxygen species-mediated PINK1/Parkin pathway.},
journal = {Ecotoxicology and environmental safety},
volume = {284},
number = {},
pages = {116954},
doi = {10.1016/j.ecoenv.2024.116954},
pmid = {39208572},
issn = {1090-2414},
abstract = {Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.},
}

@article {pmid39204746,
year = {2024},
author = {Carlucci, V and Ponticelli, M and Russo, D and Labanca, F and Costantino, V and Esposito, G and Milella, L},
title = {Nutraceutical Valorization of Exhausted Olive Pomace from Olea europaea L. Using Advanced Extraction Techniques.},
journal = {Plants (Basel, Switzerland)},
volume = {13},
number = {16},
pages = {},
pmid = {39204746},
issn = {2223-7747},
support = {CUP: G49J19001350004//Regione Basilicata/ ; CUP: C31G18000210002//Regione Basilicata/ ; },
abstract = {Exhausted olive pomace (EOP) represents the principal residue of olive pomace. Several studies have optimized the extraction of specialized metabolites from the EOP of Olea europaea L., but a comparison between different extractive methods has not been made. For this reason, the present investigation aims to compare four different extractive methods by using water and 15% ethanol/water as extractive solvents. Specifically, based on extract antioxidant activity, the methods compared were maceration (MAC), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and Accelerated Solvent Extraction (ASE). Between these, the UAE and ASE hydroalcoholic EOP extracts were demonstrated to have the highest antioxidant activity. Subsequently, these extracts were investigated for their hypoglycemic and antiradical activity using in vitro cell-free and cell-based assays, respectively. ASE hydroalcoholic EOP extract demonstrated the greatest ability to inhibit the α-amylase enzyme and an in vitro antioxidant activity comparable to N-acetyl cysteine in HepG2 cells. UAE and ASE extracts' phytochemical characterization was also performed, identifying seven phenolic compounds, including 3-hydroxytyrosol, tyrosol, and, for the first time, salidroside. The ASE hydroalcoholic EOP extract was the richest from a phytochemical point of view, thus confirming its major biological activity. Therefore, ASE and 15% ethanol/water may represent the best extractive method for EOP nutraceutical valorization.},
}

@article {pmid39196852,
year = {2024},
author = {Zhao, Q and Hu, Z and Wang, A and Ding, Z and Zhao, G and Wang, X and Li, W and Peng, Y and Zheng, J},
title = {Correlation of Vanillin-Induced Cytotoxicity with CYP3A-Mediated Metabolic Activation.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.4c03060},
pmid = {39196852},
issn = {1520-5118},
abstract = {Vanillin (VAN) is a common flavoring agent that can cause liver damage when ingested in large amounts. Nevertheless, the precise processes responsible for its toxicity remain obscure. The present research aimed to examine the metabolic activation of VAN and establish a potential correlation between its reactive metabolites and its cytotoxicity. In rat liver microsomes incubated with VAN, reduced glutathione/N-acetylcysteine (GSH/NAC), and nicotinamide adenine dinucleotide phosphate (NADPH), two conjugates formed from GSH and one conjugate derived from NAC were identified. We also discovered one GSH conjugate in both the bile obtained from rats and the rat primary hepatocytes that were subjected to VAN exposure. Additionally, the NAC conjugate exerted in the urine of VAN-treated rats was observed. These results indicate that a quinone intermediate was produced from VAN both in vitro and in vivo. Next, we identified CYP3A as the main enzyme that initiated the bioactive pathway of VAN. After the activity of CYP3A was selectively inhibited by ketoconazole (KTZ), the generation of the GSH conjugate declined in hepatocytes exposed to VAN. Furthermore, the vulnerability to VAN-induced toxicity was alleviated by KTZ in hepatocytes. Thus, we propose that the cytotoxicity of VAN may derive from metabolic activation triggered by CYP3A.},
}

@article {pmid39195722,
year = {2024},
author = {Wang, Z and Wang, Q and Gong, X},
title = {Unveiling the Mysteries of Contrast-Induced Acute Kidney Injury: New Horizons in Pathogenesis and Prevention.},
journal = {Toxics},
volume = {12},
number = {8},
pages = {},
pmid = {39195722},
issn = {2305-6304},
support = {No.82074387//National Natural Science Foundation of China/ ; No.81873280//National Natural Science Foundation of China/ ; No.20Y21902200//Shanghai Science and Technology Development Foundation/ ; },
abstract = {The utilization of contrast media (CM) in clinical diagnostic imaging and interventional procedures has escalated, leading to a gradual increase in the incidence of contrast-induced acute kidney injury (CI-AKI). Presently, the scarcity of effective pharmacological treatments for CI-AKI poses significant challenges to clinical management. Firstly, we explore the pathogenesis of CI-AKI in this review. Beyond renal medullary ischemia and hypoxia, oxidative stress, cellular apoptosis, and inflammation, emerging mechanisms such as ferroptosis, release of neutrophil extracellular traps (NETs), and nitrosative stress, which offer promising avenues for the management of CI-AKI, are identified. Secondly, a comprehensive strategy for the early prevention of CI-AKI is introduced. Investigating the risk factors associated with CI-AKI is essential for the timely identification of high-risk groups. Additionally, exploring early sensitive biomarkers is crucial for early diagnosis. A synergistic approach that combines these sensitive biomarkers, CI-AKI risk factors, and disease risk prediction models enhances both the accuracy and efficiency of early diagnostic processes. Finally, we explore recent pharmacological and non-pharmacological interventions for the management of Cl-AKI. Beyond the traditional focus on the antioxidant N-acetylcysteine (NAC), we look at active compounds from traditional Chinese medicine, including tetramethylpyrazine (TMP), salvianolic acid B (Sal B), as well as emerging preventive medications like N-acetylcysteine amide (NACA), alprostadil, and others, which all showed potential benefits in animal and clinical studies for CI-AKI prevention. Furthermore, innovative strategies such as calorie restriction (CR), enhanced external counterpulsation (EECP), and mesenchymal stem cell therapy are highlighted as providing fresh insights into Cl-AKI prevention and management.},
}

@article {pmid39195687,
year = {2024},
author = {Podobnik, B and Demšar, L and Šarc, L and Jerin, A and Osredkar, J and Trontelj, J and Roškar, R and Brvar, M},
title = {N-Acetylcysteine Ineffective in Alleviating Hangover from Binge Drinking: A Clinical Study.},
journal = {Toxics},
volume = {12},
number = {8},
pages = {},
pmid = {39195687},
issn = {2305-6304},
support = {P3-0019//Slovenian Research Agency grants/ ; 20200175//University Medical Centre Ljubljana/ ; },
abstract = {Alcohol hangover (veisalgia) is a fairly common phenomenon. The pathogenesis of veisalgia is not understood and treatment has not yet been established. Occasionally, students take N-acetylcysteine (NAC) before binge drinking to alleviate hangover. The aim of this study was to evaluate the effect of NAC on serum levels of electrolytes, enzymes, oxidative stress biomarkers and symptoms of veisalgia in binge drinking. In this randomized, double-blind, placebo-controlled study, healthy students were randomly assigned into two groups: one receiving NAC and the other receiving a placebo. Blood samples were taken before drinking, 30 min after a 1.5 h long drinking session, and the subsequent morning. Serum levels of electrolytes, urea, enzymes, ethanol, 8-Hydroxydeoxyguanosine (8-OHdG) and N-epsilon-hexanoyl-lysine were measured. The participants completed the Acute Hangover Severity Scale (AHSS) assessment based on symptoms, and 40 students (20 male), aged 23 ± 2 years, were included in the study. Their mean blood ethanol concentration was 1.4 g/kg. Serum sodium levels were increased after drinking, and urea decreased the following morning compared to their levels before drinking in both groups. Serum 8-OHdG levels were increased after drinking and remained elevated until the following morning, compared to the levels before drinking, in both groups. NAC had no effect on sodium, urea and 8-OHdG levels or the symptoms of veisalgia. In conclusion, binge drinking causes a transient increase in serum sodium and as a prolonged increase in oxidative marker 8-OHdG levels. NAC had no effect on the sodium and 8-OHdG levels.},
}

@article {pmid39192169,
year = {2024},
author = {Sun, C and Wang, Q and Li, P and Dong, R and Lei, Y and Hu, Y and Yan, Y and Song, G},
title = {The ROS Mediates MCUb in Mitochondria-Regulated Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {39192169},
issn = {1559-0720},
support = {2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 2023AB049//Corps Science and Technology Planning Project/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 21966027, 81560536, and 32060125//National Natural Science Foundation of China/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; 2023CB008-18//Youth Science and Technology Innovation Talents Project of Xinjiang Production and Construction Corps/ ; },
abstract = {Titanium dioxide nanoparticles (TiO2 NPs) can cause mitochondrial apoptosis of TM4 cells associated with reactive oxygen species (ROS) accumulation and Ca[2+] overload, but the relations among these processes remain unclear. This study aimed to evaluate whether the accumulation of ROS caused by TiO2 NPs inhibits MCUb expression, leading to mitochondrial calcium overload and subsequent cell apoptosis through the mitochondrial pathway. TM4 cells were exposed to different concentrations of TiO2 NPs (0, 25, 50, 75, 100 μg/mL) for 24 h. We assessed cell viability, ROS level, MCUb and VDAC1 expression, mitochondrial and cytoplasmic Ca[2+] levels, mitochondrial membrane potential (MMP), apoptosis rate, and key proteins related to mitochondrial apoptosis (Bcl-2, Bax, Caspase 3, Caspase 9, p53 and Cyt c). Additionally, the effect of N-acetylcysteine (NAC) on MCUb expression, calcium homeostasis, and cell apoptosis was evaluated. Compared to control group, TiO2 NPs significantly increased ROS level, downregulated MCUb expression, elevated Ca[2+] levels in mitochondria and cytoplasm, and enhanced mitochondria-regulated apoptosis, starting from the 50 μg/mL TiO2 NPs group. However, NAC significantly increased MCUb expression, attenuated Ca[2+] levels in mitochondria and cytoplasm, and reduced mitochondria-related apoptosis. In conclusion, TiO2 NPs induced ROS accumulation, which inhibited the expression of MCUb. The decreased MCUb level led to Ca[2+] overload in mitochondria, causing TM4 cell apoptosis via the mitochondrial pathway. This research elucidates, for the first time, the role of MCUb and its relation with ROS in apoptosis of TM4 cells induced by TiO2 NPs, which supplementing the molecular mechanism of cell apoptosis caused by TiO2 NPs.},
}

@article {pmid39189858,
year = {2024},
author = {Wallis, RS and Sabi, I and Lalashowi, J and Bakuli, A and Mapamba, D and Olomi, W and Siyame, E and Ngaraguza, B and Chimbe, O and Charalambous, S and Rachow, A and Ivanova, O and Zurba, L and Myombe, B and Kunambi, R and Hoelscher, M and Ntinginya, N and Churchyard, G},
title = {Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.},
journal = {NEJM evidence},
volume = {3},
number = {9},
pages = {EVIDoa2300332},
doi = {10.1056/EVIDoa2300332},
pmid = {39189858},
issn = {2766-5526},
mesh = {Humans ; *Acetylcysteine/administration & dosage/therapeutic use ; Male ; *Tuberculosis, Pulmonary/drug therapy ; Female ; Adult ; Prospective Studies ; *Antitubercular Agents/therapeutic use/administration & dosage ; *Glutathione/blood ; Middle Aged ; Lung/drug effects/microbiology/physiopathology ; Sputum/microbiology ; Treatment Outcome ; Respiratory Function Tests ; Young Adult ; },
abstract = {BACKGROUND: Tuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes.

METHODS: This prospective, randomized, controlled trial nested within the TB SEQUEL cohort study enrolled 140 adults with moderate or far-advanced tuberculosis. Participants were randomly assigned 1:1 to standard therapy with or without 1200 mg of oral NAC twice daily for days 1 to 112. Clinical evaluations, sputum culture, and spirometry were performed at specified intervals through day 168, after which participants returned to the TB SEQUEL cohort. The primary outcome was culture conversion. Secondary outcomes included whole-blood glutathione levels and lung function.

RESULTS: Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum Mycobacterium tuberculosis (MTB) infection burdens. NAC increased glutathione levels (NAC × day interaction, 8.48; 95% confidence interval [CI], 1.93 to 15.02) but did not increase stable culture conversion (hazard ratio, 0.84; 95% CI, 0.59 to 1.20; P=0.33). NAC treatment was associated with improved recovery of lung function (NAC × month, 0.49 [95% CI, 0.02 to 0.95] and 0.42 [95% CI, -0.06 to 0.91] for forced vital capacity and forced expiratory volume in the first second, respectively, as percentages of predicted values). The effects of NAC on lung function were greatest in participants with severe baseline lung impairment and appeared to persist beyond the period of NAC administration. Rates of serious or grade 3 to 4 nonserious adverse events did not differ between the groups.

CONCLUSIONS: Despite increasing whole-blood glutathione levels, NAC did not affect eradication of MTB infection in adults with pulmonary tuberculosis that was moderate to far advanced. Secondary outcomes of lung function showed changes that merit further investigation. (Funded by TB SEQUEL grant 01KA1613 of the German Ministry for Education and Research, the Health Africa Project, and the German Center for Infection Research; ClinicalTrials.gov number, NCT03702738.).},
}

Humans
*Acetylcysteine/administration & dosage/therapeutic use
Male
*Tuberculosis, Pulmonary/drug therapy
Female
Adult
Prospective Studies
*Antitubercular Agents/therapeutic use/administration & dosage
*Glutathione/blood
Middle Aged
Lung/drug effects/microbiology/physiopathology
Sputum/microbiology
Treatment Outcome
Respiratory Function Tests
Young Adult

@article {pmid39189572,
year = {2024},
author = {Sarıtaş, TB and Ertürk, C and Büyükdoğan, H and Yıldırım, B and Gündüz, N and Selek, Ş},
title = {Effects of N-acetylcysteine on sciatic nerve healing: A histopathological, functional, and biochemical study of the rat sciatic nerve.},
journal = {Joint diseases and related surgery},
volume = {35},
number = {3},
pages = {618-627},
doi = {10.52312/jdrs.2024.1784},
pmid = {39189572},
issn = {2687-4792},
mesh = {Animals ; *Acetylcysteine/pharmacology/therapeutic use ; *Rats, Wistar ; Male ; *Sciatic Nerve/drug effects/pathology/injuries ; *Nerve Regeneration/drug effects ; Rats ; Antioxidants/pharmacology ; Disease Models, Animal ; Wound Healing/drug effects ; Peripheral Nerve Injuries/drug therapy/pathology ; Recovery of Function/drug effects ; },
abstract = {OBJECTIVES: This study aims to evaluate the histopathological, biochemical, and functional effects of N-acetylcysteine (NAC), which has antioxidant, anti-inflammatory, and cytoprotective activity, on nerve regeneration in rats with sciatic nerve crush (axonotmesis) injury.

MATERIALS AND METHODS: This study used 16 male Wistar rats, which were divided into treatment and control groups. A standard axonotmesis-type surgical injury was induced in the left sciatic nerves of all rats. The treatment group was given 300 mg/kg of intraperitoneal NAC once a day, whereas the control group received an equal volume of saline solution. After conducting gait analyses, the sciatic functional index (SFI) was used for functional assessment. After gait analysis, all animals were euthanized. Blood samples were examined biochemically. The left sciatic nerves and left triceps surae muscles were examined histopathologically.

RESULTS: Histopathologically, the thickness of the perineurium, axonal degeneration, axonolysis, edema, inflammation, muscle atrophy, and muscle degeneration were all significantly lower in the treatment group (p<0.05). Functionally, SFI-1, SFI-2, and SFI-3 were significantly higher in the treatment group (p<0.05). Biochemically, while the native thiol level and native thiol/total thiol ratio were significantly higher in the treatment group (p<0.003), the disulfide/total thiol ratio was significantly higher in the control group (p<0.005). Significant correlations were found between six of the seven gait parameters and the histopathological findings (p<0.05).

CONCLUSION: Our study results suggest that NAC may contribute positively to the histopathological and functional recovery of sciatic nerve injury in rats. Furthermore, NAC may have an antioxidant effect on thiol-disulfide homeostasis at a biochemical level. We believe that NAC has a stimulatory effect on healing following nerve injuries.},
}

Animals
*Acetylcysteine/pharmacology/therapeutic use
*Rats, Wistar
Male
*Sciatic Nerve/drug effects/pathology/injuries
*Nerve Regeneration/drug effects
Rats
Antioxidants/pharmacology
Disease Models, Animal
Wound Healing/drug effects
Peripheral Nerve Injuries/drug therapy/pathology
Recovery of Function/drug effects

@article {pmid39189388,
year = {2024},
author = {Adel, O and El-Sherbiny, HR and M Shahat, A and Ismail, ST},
title = {N-Acetylcysteine Supplementation Improves Testicular Haemodynamics, Testosterone Levels, Seminal Antioxidant Capacity and Semen Quality in Heat-Stressed Goat Bucks.},
journal = {Reproduction in domestic animals = Zuchthygiene},
volume = {59},
number = {8},
pages = {e14709},
doi = {10.1111/rda.14709},
pmid = {39189388},
issn = {1439-0531},
mesh = {Male ; Animals ; *Goats/physiology ; *Testis/drug effects ; *Testosterone/blood ; *Acetylcysteine/pharmacology/administration & dosage ; *Antioxidants/pharmacology ; *Semen Analysis/veterinary ; *Hemodynamics/drug effects ; *Dietary Supplements ; *Semen/drug effects ; Nitric Oxide/metabolism ; Hot Temperature ; },
abstract = {Heat stress (HS) disrupts testicular homeostasis because of oxidative stress. N-acetylcysteine (NAC) is a thiol compound with antioxidants, anti-inflammatory and anti-apoptotic properties. As a sequel, this research aimed to assess the ameliorative effects of NAC supplementation on the reproductive performance of goat bucks kept under environmental HS. Primarily, Doppler examination as well as semen collection and evaluation were conducted on 12 mature bucks for 2 weeks (W) as pre-heat stress control (W1 and W2) during winter (February 2023). The temperature-humidity index (THI) was 63.4-64.3 (winter season). Then during summer HS conditions (from the beginning of July till the end of August 2023) bucks were assessed before NAC supplementation (W0), afterwards they were arbitrarily assigned into two groups. The control group (CON; n = 6) received the basal diet while the NAC group (n = 6) received the basal diet in addition to oral NAC daily for 7 weeks (W1-W7). The THI was 78.1-81.6 (summer season). Testicular blood flow parameters, serum concentration of nitric oxide (NO) and testosterone were measured. Additionally, total antioxidant capacity (TAC) and malondialdehyde (MDA) content in seminal plasma and semen quality parameters were evaluated. There were marked reductions (p < 0.05) in the resistive index (RI; W1, W4 and W5), pulsatility index (PI; W2 and W4-W7), and systolic/diastolic ratio (S/D; W4-W7) in the NAC group compared to the CON group. Furthermore, testosterone and NO levels were higher (p < 0.01 and p < 0.05, respectively) in the NAC group (W2, W3, W5 and W3-W5, respectively). Seminal plasma TAC increased (p < 0.05) and MDA decreased (p < 0.05) in the NAC group (W2, W4 and W5) compared to the CON group. Moreover, there were marked improvements (p < 0.05) in semen quality parameters (mass motility, total motility, viability and normal morphology) in the NAC group. In conclusion, oral NAC supplementation could be used to enhance the reproductive performance of goat bucks during HS conditions which is supported by remarkable enhancement in testicular haemodynamics, NO, testosterone levels and semen quality parameters.},
}

Male
Animals
*Goats/physiology
*Testis/drug effects
*Testosterone/blood
*Acetylcysteine/pharmacology/administration & dosage
*Antioxidants/pharmacology
*Semen Analysis/veterinary
*Hemodynamics/drug effects
*Dietary Supplements
*Semen/drug effects
Nitric Oxide/metabolism
Hot Temperature

@article {pmid39182712,
year = {2024},
author = {Jiang, P and Hu, S and Zheng, C and Liu, Y and Zhang, Q and Dou, L},
title = {Cryopreservation of Human Teeth Using Vitrification method with Cryoprotectant Cocktails and N-acetylcysteine for Banking and Clinical Applications.},
journal = {Cryobiology},
volume = {},
number = {},
pages = {104959},
doi = {10.1016/j.cryobiol.2024.104959},
pmid = {39182712},
issn = {1090-2392},
abstract = {Preserving freshly-extracted healthy human teeth offers an optional resource for potential tooth transplantation and cell therapy. This study aimed to assess the impact of vitrification, utilizing a blend of cryoprotectant agents and N-acetylcysteine (NAC), on the cryopreservation of periodontal ligament tissues, and investigate the underlying mechanisms of NAC on the tooth cryopreservation. Periodontal ligament cells were isolated from freshly-extracted healthy human permanent teeth, and cell sheets of PDLCs were fabricated. The samples including cell sheets, freshly-extracted human and rat teeth were cryopreserved with or without NAC for three months. The viability, ROS level, gene expressions and microstructure of PDLCs within cell sheets were assessed. The expression of SOD-2, Caspase3, LC3A/B and Catalase were evaluated through western blotting. Histological assessments of cryopreserved cell sheets and teeth were conducted. PDLCs were isolated from cryopreserved teeth, and their immunophenotype and differentiation ability were evaluated. The data was analyzed using one-way analysis of variance. The vitrification method showed good performance in preserving the viability and differentiation potential of PDLCs. Cryopreservation supplemented with NAC improved the survival rate of PDLCs, enhanced osteogenic differentiation ability, upregulated the expression of SOD-2 and Catalase, and inhibited cell apoptosis. Additionally, mRNA sequencing analysis revealed a significant activation of the PI3K-AKT pathway following cryopreservation via vitrification. Adding a PI3K-AKT activator improved the survival rates of PDLCs post-cryopreservation. The vitrification strategy combining various CPAs and NAC proved to be feasible for tooth cryopreservation. Targeting the PI3K-AKT pathway may improve the efficacy of tooth cryopreservation.},
}

@article {pmid39182421,
year = {2024},
author = {Lu, J and Zhao, P and Ding, X and Li, H},
title = {N-acetylcysteine stimulates the proliferation and differentiation in heat-stressed skeletal muscle cells.},
journal = {Journal of thermal biology},
volume = {124},
number = {},
pages = {103958},
doi = {10.1016/j.jtherbio.2024.103958},
pmid = {39182421},
issn = {0306-4565},
abstract = {N-acetylcysteine (NAC) is known for its beneficial effects on health due to its antioxidant and antiapoptotic properties. This study explored the protective effects of NAC against oxidative stress in heat-stressed (HS) skeletal muscle cells and its role in promoting muscle development. NAC reduced the heat shock response by decreasing the expression of heat shock protein 70 (HSP70) in HS-induced muscle cells during proliferation and differentiation. NAC also mitigated HS-induced oxidative stress via increasing the antioxidant enzyme levels and reducing oxidant enzyme levels. Treatment with NAC at 2 mM increased cell viability from 43.68% ± 5.14%-66.69% ± 14.43% and decreased the apoptosis rate from 7.89% ± 0.53%-5.17% ± 0.11% in skeletal muscle cells. Additionally, NAC promoted the proliferation and differentiation of HS-induced skeletal muscle cells by upregulating the expression of PAX7, MYF5, MRF4 and MYHC. These findings suggest that NAC alleviates HS-induced oxidative damage in skeletal muscle cells and support muscle development.},
}

@article {pmid39178962,
year = {2024},
author = {Zhao, Z and Yi, S and E, H and Jiang, L and Zhou, C and Zhao, X and Yang, L},
title = {α-amanitin induce inflammatory response by activating ROS/NF-κB-NLRP3 signaling pathway in human hepatoma HepG2 cells.},
journal = {Chemosphere},
volume = {364},
number = {},
pages = {143157},
doi = {10.1016/j.chemosphere.2024.143157},
pmid = {39178962},
issn = {1879-1298},
abstract = {α-amanitin (AMA) is a hepatotoxic mushroom toxin responsible for over 90% of mushroom poisoning fatalities worldwide, seriously endangering human life and health. Few evidences have indicated that AMA leads to inflammatory responses and inflammatory infiltration in vitro and in vivo. However, the molecular mechanism remains unknown. In this study, human hepatocellular carcinomas cells (HepG2) were exposed to AMA at various concentrations for short period of times. Results revealed that AMA increased ROS production and elevated the releases of malondialdehyde (MDA) and lactate dehydrogenase (LDH), resulting in oxidative damage in HepG2 cells. Also, AMA exposure significantly increased the secreted levels of inflammatory cytokines and activated the NLRP3 inflammasome. The inflammatory responses were reversed by NLRP3 inhibitor MCC950 and NF-κB inhibitor Bay11-7082. Additionally, N-acetylcysteine (NAC) blocked the upregulation of the NF-κB/NLRP3 signaling pathway and remarkably alleviated the inflammatory response. These results demonstrated that AMA could induce inflammation through activating the NLRP3 inflammasome triggered by ROS/NF-κB signaling pathway. Our research provides new insights into the molecular mechanism of AMA-induced inflammation damage and may contribute to establish new prevention strategies for AMA hepatotoxicity.},
}

@article {pmid39178616,
year = {2024},
author = {Zhang, C and Sun, X and Wu, D and Wang, G and Lan, H and Zheng, X and Li, S},
title = {IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage.},
journal = {Theriogenology},
volume = {229},
number = {},
pages = {147-157},
doi = {10.1016/j.theriogenology.2024.08.023},
pmid = {39178616},
issn = {1879-3231},
abstract = {Calcium ions (Ca[2+]) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca[2+] levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca[2+] ([Ca[2+]]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. The results of the Duolink II in situ proximity ligation assay (PLA) revealed a weakened pairwise interaction between IP3R1-GRP75 and VDAC1 and a significantly increased interaction between GRP75 and VDAC1 after IP3R1 interference, resulting in the accumulation of large amounts of [Ca[2+]]m. These changes led to mitochondrial oxidative stress, increased the levels of reactive oxygen species (ROS) and reduced ATP production, which hindered the maturation and late development of porcine oocytes and induced apoptosis. Nevertheless, after treat with [Ca[2+]]m chelating agent ruthenium red (RR) or ROS scavenger N-acetylcysteine (NAC), the oocytes developmental abnormalities, oxidative stress and apoptosis caused by Ca[2+] overload were improved. In conclusion, our results indicated IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage.},
}

@article {pmid39175643,
year = {2024},
author = {Sabbaghziarani, F and Soleimani, P and Eynshikh, FR and Zafari, F and Aali, E},
title = {Reduced ischemia-reperfusion oxidative stress injury by melatonin and N-acetylcysteine in the male rat brain.},
journal = {IBRO neuroscience reports},
volume = {17},
number = {},
pages = {131-137},
pmid = {39175643},
issn = {2667-2421},
abstract = {Middle cerebral artery occlusion (MCAO) is a model for inducing ischemic stroke in rodents, leading to devastating brain damage. Oxidative stress (OS) plays a crucial role in the pathogenesis of ischemia. In this study, the effect of melatonin and N-acetylcysteine on ischemia-reperfusion-induced oxidative stress injury in the cerebral cortex of male rats was investigated. 30 male Wistar rats were divided into sham, ischemic, NAC, melatonin and NAC + melatonin groups. All groups, except the sham group, underwent MCAO on the left side, and the treatment groups received intraperitoneal injections of either 50 mg/kg N-acetylcysteine (NAC) or 5 mg/kg melatonin or a combination of both 24 and 48 hours later. At 24 and 72 hours after surgery, the animals were examined for sensory and motor activity. The cerebral cortex was dissected after sacrificing the rats, infarct volume estimated and the concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nuclear factor erythroid-2 related factor 2 (Nrf2) were analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicate that the NAC + melatonin group exhibited elevated sensory-motor activity and a reduced infarct volume rate in comparison to the ischemic group (p≤ 0.05). Compared to the ischemic group, the NAC + melatonin group showed a significant increase in SOD concentration and a significant decrease in MDA (p≤ 0.05). It can therefore be concluded that the simultaneous administration of NAC and melatonin can reduce the cerebral infarction volume, and improve neurological functions by modulating SOD and MDA.},
}

@article {pmid39166871,
year = {2024},
author = {Wilson, PR and Bridges, KH and Scofield, M and Wilson, SH},
title = {Perioperative N-acetylcysteine: evidence and indications.},
journal = {Pain management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17581869.2024.2388504},
pmid = {39166871},
issn = {1758-1877},
abstract = {Nonopioid analgesics serve to improve analgesia and limit side effects and risks of perioperative opioids. N-acetylcysteine (NAC), the primary treatment of acetaminophen toxicity, may have perioperative indications, including analgesia. NAC impacts glutathione synthesis, oxidant scavenging, glutamate receptor modulation and neuroinflammation. Potential perioperative benefits include arrhythmia prevention after cardiac surgery, decreased contrast-induced nephropathy, improved post-transplant liver function and superior pulmonary outcomes with general anesthesia. NAC may improve perioperative analgesia, with some studies displaying a reduction in postoperative opioid use. NAC is generally well tolerated with an established safety profile. NAC administration may predispose to gastrointestinal effects, while parenteral administration may carry a risk of anaphylactoid reactions, including bronchospasm. Larger randomized trials may clarify the impact of NAC on perioperative analgesic outcomes.},
}

@article {pmid39159553,
year = {2024},
author = {Kim, NY and Dukanya, D and Sethi, G and Girimanchanaika, SS and Yang, J and Nagaraja, O and Swamynayaka, A and Vishwanath, D and Venkantesha, K and Basappa, S and Chinnathambi, A and Alharbi, SA and Madegowda, M and Sukhorukov, A and Pandey, V and Lobie, PE and Basappa, B and Ahn, KS},
title = {Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells.},
journal = {Translational oncology},
volume = {49},
number = {},
pages = {102101},
doi = {10.1016/j.tranon.2024.102101},
pmid = {39159553},
issn = {1936-5233},
abstract = {Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.},
}

@article {pmid39158930,
year = {2024},
author = {Li, J and Jiang, L and Zhao, K and Tang, Y and Yuan, X and Xu, Y},
title = {Myeloid-derived TLR4-TRIF signaling pathway mediates oxidative stress in LPS/D-GalN-induced acute liver failure.},
journal = {Shock (Augusta, Ga.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/SHK.0000000000002438},
pmid = {39158930},
issn = {1540-0514},
abstract = {BACKGROUND: Acute liver failure (ALF) is a severe clinical syndrome characterized by massive hepatocyte death in a short time due to viruses, drugs, alcohol, or other factors. Oxidative stress is an important pathogenic mechanism of ALF. LPS-induced internalization of toll-like receptor 4 (TLR4) and the subsequent activation of the toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) signaling pathway widely mediate inflammatory responses in a series of diseases. However, whether the TLR4-TRIF signaling pathway contributes to ALF by mediating oxidative stress processes remains unclear.

METHODS: An ALF mouse model was induced by Lipopolysaccharide (LPS)/D-galactosamine (D-GalN). TLR4-TRIF systemic knockout mice and TLR4 conditional knockout mice were used to determine the role of the TLR4-TRIF signaling pathway in ALF. The effects of TLR4 or TRIF deficiency on oxidative stress were investigated. In addition, we examined the protective role of the clodronate liposomes (macrophage scavengers) and the antioxidant N-acetylcysteine (NAC) in ALF.

RESULTS: TLR4 or TRIF deficiency significantly alleviated LPS/D-GalN-induced lethality, hepatic dysfunction, and hepatic pathologic injury, which was dependent on myeloid-derived TLR4. Hence, macrophage clearance exhibits a similar protective effect. Mechanically, TLR4 or TRIF deficiency was observed to inhibit oxidative stress by increasing glutathione, while decreasing malondialdehyde, 8-hydroxy-2-deoxyguanosine, and γ-H2AX. Therefore, the pharmacologic antioxidant NAC exhibited significant hepato-protective effects.

CONCLUSIONS: Targeting myeloid-derived TLR4-TRIF signaling pathway or antioxidant therapy may be a potential therapeutic direction to treat ALF.},
}

@article {pmid39148391,
year = {2024},
author = {Yang, K and Wu, Y and Zhang, R and Lei, XP and Kang, L and Dong, WB},
title = {[Role of reactive oxygen species/silent information regulator 1 in hyperoxia-induced bronchial epithelial cell injury].},
journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics},
volume = {26},
number = {8},
pages = {852-860},
pmid = {39148391},
issn = {1008-8830},
mesh = {*Sirtuin 1/metabolism/physiology/genetics ; Humans ; *Reactive Oxygen Species/metabolism ; *Hyperoxia/complications/metabolism ; *Epithelial Cells/metabolism ; *Bronchi/metabolism ; Mitochondria/metabolism ; Cells, Cultured ; Cell Line ; },
abstract = {OBJECTIVES: To investigate the effect of reactive oxygen species (ROS)/silent information regulator 1 (SIRT1) on hyperoxia-induced mitochondrial injury in BEAS-2B cells.

METHODS: The experiment was divided into three parts. In the first part, cells were divided into H0, H6, H12, H24, and H48 groups. In the second part, cells were divided into control group, H48 group, H48 hyperoxia+SIRT1 inhibitor group (H48+EX 527 group), and H48 hyperoxia+SIRT1 agonist group (H48+SRT1720 group). In the third part, cells were divided into control group, 48-hour hyperoxia+N-acetylcysteine group (H48+NAC group), and H48 group. The ROS kit was used to measure the level of ROS. Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins. Transmission electron microscopy was used to observe the morphology of mitochondria.

RESULTS: Compared with the H0 group, the H6, H12, H24, and H48 groups had a significantly increased fluorescence intensity of ROS (P<0.05), the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins (P<0.05), and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins (P<0.05). Compared with the H48 group, the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio (P<0.05), and the H48+EX 527 group had a significant reduction in the mitochondrial area (P<0.05). Compared with the H48 group, the H48+NAC group had a significantly decreased fluorescence intensity of ROS (P<0.05) and significantly increased levels of SIRT1 protein, mitochondria-related proteins, mitochondrial area, and mitochondrial aspect ratio (P<0.05).

CONCLUSIONS: The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.},
}

*Sirtuin 1/metabolism/physiology/genetics
Humans
*Reactive Oxygen Species/metabolism
*Hyperoxia/complications/metabolism
*Epithelial Cells/metabolism
*Bronchi/metabolism
Mitochondria/metabolism
Cells, Cultured
Cell Line

@article {pmid39148029,
year = {2024},
author = {Wu, C and Li, Y and Liu, S and Wang, L and Wang, X},
title = {Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling.},
journal = {BMC cardiovascular disorders},
volume = {24},
number = {1},
pages = {431},
pmid = {39148029},
issn = {1471-2261},
support = {SB201901060；YJSCX202290Y//Medical Science and Technology Tackling Program of Henan Province (SB201901060) and Postgraduate research innovation program (YJSCX202290Y)./ ; SB201901060；YJSCX202290Y//Medical Science and Technology Tackling Program of Henan Province (SB201901060) and Postgraduate research innovation program (YJSCX202290Y)./ ; },
mesh = {Animals ; Humans ; Antigens, CD/metabolism ; Antioxidants/pharmacology ; *Atherosclerosis/drug therapy/etiology/pathology ; Cadherins/metabolism ; Cells, Cultured ; Disease Models, Animal ; *Endothelial-Mesenchymal Transition/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism/drug effects/pathology ; *Hyperhomocysteinemia/drug therapy/metabolism/complications ; *Iridoid Glucosides/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *NF-kappa B/metabolism ; Oxidative Stress/drug effects ; *Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Transcription Factor RelA/metabolism ; Mice ; },
abstract = {BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS). Endothelial mesenchymal transition (EndMT) refers to the process in which endothelial cells lose endothelial cell morphology and characteristic gene expression, and acquire phenotypic characteristics and gene expression related to mesenchymal cells. Numerous studies have confirmed that EndMT is involved in the formation of atherosclerosis. Catalpol is one of the active components of Rehmannia, which has antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Studies have shown that catalpol can reduce atherosclerotic plaque induced by high sugar or fat. However, the effect of catalpol on HHCY-induced EndMT is unclear.

METHODS AND RESULTS: In vitro HHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a cell model, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. In vivo C57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The results showed that hhcy could induce morphological transformation of endothelial cells into mesenchymal cells, increase intracellular ROS content, up-regulate α-SMA, N-cadherin, p-p65 protein expression, down-regulate VE-cadherin, CD31 protein expression, induce pathological changes of aortic root endothelium, and increase aortic endothelial ROS content. Catalpol reversed these hhcy induced outcomes.

CONCLUSIONS: Catalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.},
}

Animals
Humans
Antigens, CD/metabolism
Antioxidants/pharmacology
*Atherosclerosis/drug therapy/etiology/pathology
Cadherins/metabolism
Cells, Cultured
Disease Models, Animal
*Endothelial-Mesenchymal Transition/drug effects
Human Umbilical Vein Endothelial Cells/metabolism/drug effects/pathology
*Hyperhomocysteinemia/drug therapy/metabolism/complications
*Iridoid Glucosides/pharmacology/therapeutic use
Mice, Inbred C57BL
*NF-kappa B/metabolism
Oxidative Stress/drug effects
*Reactive Oxygen Species/metabolism
Signal Transduction/drug effects
Transcription Factor RelA/metabolism
Mice

@article {pmid39146674,
year = {2024},
author = {Wu, H and Huo, H and Li, H and Zhang, H and Li, X and Han, Q and Liao, J and Tang, Z and Guo, J},
title = {N-acetylcysteine combined with insulin therapy can reduce myocardial injury induced by type 1 diabetes through the endoplasmic reticulum pathway.},
journal = {Tissue & cell},
volume = {90},
number = {},
pages = {102515},
doi = {10.1016/j.tice.2024.102515},
pmid = {39146674},
issn = {1532-3072},
mesh = {Animals ; *Diabetes Mellitus, Type 1/drug therapy/metabolism/pathology/complications ; *Insulin/pharmacology/metabolism ; Dogs ; *Endoplasmic Reticulum/metabolism/drug effects ; *Acetylcysteine/pharmacology ; *Myocardium/metabolism/pathology ; Endoplasmic Reticulum Chaperone BiP ; Endoplasmic Reticulum Stress/drug effects ; Apoptosis/drug effects ; Male ; Signal Transduction/drug effects ; },
abstract = {With the development of Type 1 diabetes mellitus (T1DM), various complications can be caused. Hyperglycemia affects the microenvironment of cardiomyocytes, changes endoplasmic reticulum homeostasis, triggers unfolding protein response and eventually promotes myocardial apoptosis. However, insulin therapy alone cannot effectively combat the complications caused by T1DM. Forty adult beagles were randomly divided into five groups: control group, diabetes mellitus group, insulin group, insulin combined with NAC group, and NAC group. 24-hour blood glucose, 120-day blood glucose, 120-day body weight, and serum FMN content were observed, furthermore, hematoxylin-eosin staining, Periodic acid Schiff reagent staining, and Sirius red staining of the myocardium were evaluated. The protein expressions of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase 3, Bcl2, and Bax were detected. Results of the pathological section of myocardial tissue indicated that insulin combined with NAC therapy could improve myocardial pathological injury and glycogen deposition. Additionally, insulin combined with NAC therapy down-regulates the expression of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase3, and Bax. These findings suggest that NAC has a phylactic effect on myocardial injury in beagles with T1DM, and the mechanism may be related to the improvement of endoplasmic reticulum stress-induced apoptosis.},
}

Animals
*Diabetes Mellitus, Type 1/drug therapy/metabolism/pathology/complications
*Insulin/pharmacology/metabolism
Dogs
*Endoplasmic Reticulum/metabolism/drug effects
*Acetylcysteine/pharmacology
*Myocardium/metabolism/pathology
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress/drug effects
Apoptosis/drug effects
Male
Signal Transduction/drug effects

@article {pmid39144112,
year = {2024},
author = {Husain, MO and Chaudhry, IB and Khoso, AB and Husain, MI and Ansari, MA and Mehmood, N and Naqvi, HA and Nizami, AT and Talib, U and Rajput, AH and Bassett, P and Foussias, G and Deakin, B and Husain, N},
title = {Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.},
journal = {Schizophrenia bulletin open},
volume = {5},
number = {1},
pages = {sgae004},
pmid = {39144112},
issn = {2632-7899},
abstract = {BACKGROUND AND HYPOTHESIS: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia.

STUDY DESIGN: A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed.

STUDY RESULTS: We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes.

CONCLUSIONS: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT03510741.},
}

@article {pmid39144108,
year = {2024},
author = {Wasserthal, S and Muthesius, A and Hurlemann, R and Ruhrmann, S and Schmidt, SJ and Hellmich, M and Schultze-Lutter, F and Klosterkötter, J and Müller, H and Meyer-Lindenberg, A and Poeppl, TB and Walter, H and Hirjak, D and Koutsouleris, N and Fallgatter, AJ and Bechdolf, A and Brockhaus-Dumke, A and Mulert, C and Philipsen, A and Kambeitz, J},
title = {N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.},
journal = {Schizophrenia bulletin open},
volume = {5},
number = {1},
pages = {sgae005},
pmid = {39144108},
issn = {2632-7899},
abstract = {BACKGROUND AND HYPOTHESIS: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients.

STUDY DESIGN: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months.

STUDY RESULTS: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups.

CONCLUSIONS: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.},
}

@article {pmid39142116,
year = {2024},
author = {Wang, Y and Guo, AL and Xu, Y and Xu, X and Yang, L and Yang, Y and Chao, L},
title = {EHDPP induces proliferation inhibition and apoptosis to spermatocyte: Insights from transcriptomic and metabolomic profiles.},
journal = {Ecotoxicology and environmental safety},
volume = {284},
number = {},
pages = {116878},
doi = {10.1016/j.ecoenv.2024.116878},
pmid = {39142116},
issn = {1090-2414},
abstract = {BACKGROUND: 2-ethylhexyldiphenyl phosphate (EHDPP) was used widespread in recent years and it was reported to impair reproductive behaviors and decrease fertility in male Japanese medaka. However, whether EHDPP causes spermatogenesis disturbance remains uncertain.

OBJECTIVES: We aimed to study the male reproductive toxicity of EHDPP and its related mechanism.

METHODS: Human spermatocyte cell line GC-2 was treated with 10 µM, 50 µM or 100 µM EHDPP for 24 h. Male CD-1 mice aged 6 weeks were given 1, 10, or 100 mg/kg/d EHDPP daily for 42 days and then euthanized to detect sperm count and motility. Proliferation, apoptosis, oxidative stress was detected in mice and cell lines. Metabolome and transcriptome were used to detect the related mechanism. Finally, anti-oxidative reagent N-Acetylcysteine was used to detect whether it could reverse the side-effect of EHDPP both in vivo and in vitro.

RESULTS: Our results showed that EHDPP inhibited proliferation and induced apoptosis in mice testes and spermatocyte cell line GC-2. Metabolome and transcriptome showed that nucleotide metabolism disturbance and DNA damage was potentially involved in EHDPP-induced reproductive toxicity. Finally, we found that excessive ROS production caused DNA damage and mitochondrial dysfunction; NAC supplement reversed the side effects of EHDPP such as DNA damage, proliferation inhibition, apoptosis and decline in sperm motility.

CONCLUSION: ROS-evoked DNA damage and nucleotide metabolism disturbance mediates EHDPP-induced germ cell proliferation inhibition and apoptosis, which finally induced decline of sperm motility.},
}

@article {pmid39139444,
year = {2024},
author = {Hanafy, DA and Willim, HA and Suwatri, WT and Sani, AA and Khouw, H and Susanti, EI and Sugisman, },
title = {Efficacy of N-acetylcysteine for Prevention of Postoperative Atrial Fibrillation Following Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
journal = {Reviews in cardiovascular medicine},
volume = {25},
number = {7},
pages = {243},
pmid = {39139444},
issn = {2153-8174},
abstract = {BACKGROUND: As the prevalence of coronary artery disease rises, the demand for coronary artery bypass grafting (CABG) increases. A common complication after CABG is postoperative atrial fibrillation (POAF), which is linked to adverse clinical outcomes. N-acetylcysteine (NAC), an antioxidant, may mitigate oxidative stress and reduce the incidence of POAF. This meta-analysis aims to investigate the efficacy of NAC in preventing POAF after CABG.

METHODS: The meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched multiple databases, including PubMed, Cochrane Library, ProQuest, and ScienceDirect, to identify relevant randomized controlled trials (RCTs). The intervention groups received perioperative NAC therapy, while the control groups received a placebo. The outcomes assessed were POAF incidence, all-cause mortality, and hospital length of stay (LOS). Review Manager 5.3 was used to conduct the meta-analysis.

RESULTS: Eleven RCTs involving 648 patients were included. The NAC group comprised 326 patients, while the control group comprised 322 patients. In the pooled analysis, patients in the NAC group had a significantly lower incidence of POAF (odds ratios (OR) = 0.57; 95% confidence intervals (CI) = 0.33 to 0.97; p = 0.04) and a shorter hospital LOS (weighted mean differences (WMD) = -0.66; 95% CI = -1.22 to -0.10; p = 0.02) compared to the control group. However, there was no significant difference in all-cause mortality.

CONCLUSIONS: The perioperative administration of NAC can effectively reduce the incidence of POAF and hospital LOS in CABG patients. However, larger RCTs are needed to confirm these findings.},
}

@article {pmid39139367,
year = {2024},
author = {Tasci, T and Orta-Yilmaz, B and Aydin, Y and Caliskan, M},
title = {N-acetylcysteine attenuates sodium arsenite-induced oxidative stress and apoptosis in embryonic fibroblast cells.},
journal = {Toxicology research},
volume = {13},
number = {4},
pages = {tfae128},
pmid = {39139367},
issn = {2045-452X},
abstract = {In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 μM to 10 μM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.},
}

@article {pmid39131009,
year = {2024},
author = {Roghani, SH and Arif, MA and Niazi, R and Mansoor, S},
title = {Naphthalene or Mothball Poisoning Manifesting as Acute Intravascular Hemolysis and Acquired Methemoglobinemia.},
journal = {Cureus},
volume = {16},
number = {7},
pages = {e64325},
pmid = {39131009},
issn = {2168-8184},
abstract = {Naphthalene is a major component of mothballs. Domestically, people use mothballs as an insect repellent. Its deliberate or accidental ingestion leading to toxicity has rarely been reported in the medical literature, despite its widespread use in Southeast Asia. Naphthalene, or mothball poisoning, is a rare but serious condition that can have detrimental effects on human health. This case report presents the clinical course of a 22-year-old male who ingested six naphthalene balls, resulting in severe symptoms including fever, abdominal pain, vomiting, jaundice, and dark-colored urine. Laboratory investigations were suggestive of acute intravascular hemolysis and methemoglobinemia. The patient was promptly admitted to the hospital, where he received supportive care along with specific treatment in the form of red blood cell transfusions, intravenous methylene blue, ascorbic acid, and N-acetyl cysteine. Through this report, the importance of raising awareness about the dangers of naphthalene poisoning and the specific treatment options available is highlighted.},
}

@article {pmid39128732,
year = {2024},
author = {Lu, X and Wu, S and Ai, H and Wu, R and Cheng, Y and Yun, S and Chang, M and Liu, J and Meng, J and Cheng, F and Feng, C and Cao, J},
title = {Sparassis latifolia polysaccharide alleviated lipid metabolism abnormalities in kidney of lead-exposed mice by regulating oxidative stress-mediated inflammation and autophagy based on multi-omics.},
journal = {International journal of biological macromolecules},
volume = {278},
number = {Pt 1},
pages = {134662},
doi = {10.1016/j.ijbiomac.2024.134662},
pmid = {39128732},
issn = {1879-0003},
abstract = {Lead is a common environmental pollutant which can accumulate in the kidney and cause renal injury. However, regulatory effects and mechanisms of Sparassis latifolia polysaccharide (SLP) on lipid metabolism abnormality in kidney exposed to lead are not clarified. In this study, mice were used to construct an animal model to observe the histopathological changes in kidney, measure lead content, damage indicators, differentially expressed metabolites (DEMs) and genes (DEGs) in key signaling pathways that cause lipid metabolism abnormalities based on lipidomics and transcriptomics, which were later validated using qPCR and western blotting. Co-treatment of Pb and N-acetylcysteine (NAC) were used to verify the link between SLP and oxidative stress. Our results indicated that treatment with SLP identified 276 DEMs (including metabolism of glycerophospholipid, sphingolipid, glycerolipid and fatty acid) and 177 DEGs (including genes related to oxidative stress, inflammation, autophagy and lipid metabolism). Notably, regulatory effects of SLP on abnormal lipid metabolism in kidney were mainly associated with oxidative stress, inflammation and autophagy; SLP could regulate abnormal lipid metabolism in kidney by reducing oxidative stress and affecting its downstream-regulated autophagy and inflammatory to alleviate renal injury caused by lead exposure. This study provides a theoretical basis for SLP intervention in lead injury.},
}

@article {pmid39128490,
year = {2024},
author = {Isaguliants, M and Zhitkevich, A and Petkov, S and Gorodnicheva, T and Mezale, D and Fridrihsone, I and Kuzmenko, Y and Kostyushev, D and Kostyusheva, A and Gordeychuk, I and Bayurova, E},
title = {Enzymatic activity of HIV-1 protease defines migration of tumor cells in vitro and enhances their metastatic activity in vivo.},
journal = {Biochimie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biochi.2024.08.009},
pmid = {39128490},
issn = {1638-6183},
abstract = {Overexpression of aspartic proteases, as cathepsin D, is an independent marker of poor prognosis in breast cancer, correlated with the incidence of clinical metastasis. We aimed to find if HIV-1 aspartic protease (PR) can play a similar role. Murine adenocarcinoma 4T1luc2 cells were transduced with lentivirus encoding inactivated drug-resistant PR, generating subclones PR20.1 and PR20.2. Subclones were assessed for production of reactive oxygen species (ROS), expression of epithelial-mesenchymal transition (EMT) factors, and in vitro migratory activity in the presence or absence of antioxidant N-acetyl cysteine and protease inhibitors. Tumorigenic activity was evaluated by implanting cells into BALB/c mice and following tumor growth by calipering and bioluminescence imaging in vivo, and metastases, by organ imaging ex vivo. Both subclones expressed PR mRNA, and PR20.2, also the protein detected by Western blotting. PR did not induce production of ROS, and had no direct effect on cell migration rate, however, treatment with inhibitors of drug-resistant PR suppressed the migratory activity of both subclones. Furthermore, expression of N-cadherin and Vimentin in PR20.2 cells and their migration were enhanced by antioxidant treatment. Sensitivity of in vitro migration to protease inhibitors and to antioxidant, known to restore PR activity, related the effects to the enzymatic activity of PR. In vivo, PR20.2 cells demonstrated higher tumorigenic and metastatic activity than PR20.1 or parental cells. Thus, HIV-1 protease expressed in breast cancer cells determines their migration in vitro and metastatic activity in vivo. This effect may aggravate clinical course of cancers in people living with HIV-1.},
}

@article {pmid39125554,
year = {2024},
author = {Wee, JH and Park, JH and Park, MW and Choi, YS and Jung, HJ},
title = {Sinus Irrigation with N-Acetylcysteine after Endoscopic Sinus Surgery for Chronic Rhinosinusitis: A Preliminary Report of a Single-Blind Randomized Controlled Trial.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {15},
pages = {},
pmid = {39125554},
issn = {2075-4418},
support = {2022101232//Chungbuk National University/ ; },
abstract = {Nasal irrigation is crucial following endoscopic sinus surgery (ESS), especially for managing chronic rhinosinusitis (CRS). This study assessed the effectiveness of N-acetylcysteine (NAC) irrigation during the post-ESS period of patients with CRS without nasal polyposis. In this prospective, single-blind randomized controlled trial, 49 patients (NAC, n = 24; saline, n = 25) undergoing ESS were assigned to receive either NAC or saline irrigations twice daily for a month. The preoperative and postoperative assessments conducted included Lund-Macka (LM) and Lund-Kennedy (LK) endoscopic scores, the Nasal Obstruction Symptom Evaluation (NOSE) scale, and the Sino-Nasal Outcome Test-20 (SNOT-20). At 2 weeks, 1 month, and 3 months after the operation, endoscopic findings and symptoms were evaluated. Both groups showed no differences in age, sex, LM and LK scores, NOSE scale, and SNOT-20 preoperatively. In terms of the endoscopic findings regarding the sinonasal mucosa after ESS, the NAC group had slightly lower scores 2 weeks, 1 month, and 3 months after the operation, but this difference was not statistically significant. The NAC group showed significant improvement in VAS scores, namely, postnasal drip (1.0, p = 0.041), smell dysfunction (0.8, p = 0.003), and crust (1.5, p = 0.034), compared to the control group's scores of 2.6, 4.7, and 3.6, respectively, 2 weeks after the operation, although no significant differences were observed in VAS scores for any symptoms 1 and 3 months after the operation. NAC was well tolerated, and no adverse events were reported. NAC irrigation showed benefits over saline irrigation in terms of improving postnasal drip, smell dysfunction, and crust after ESS for CRS without nasal polyposis in the immediate postoperative period.},
}