@article {pmid37766400,
year = {2023},
author = {Benizio, E and Moreira-Espinoza, MJ and Triquell, MF and Mezzano, L and Díaz-Luján, CM and Fretes, RE},
title = {Pro-inflammatory cytokines are modified during the multiplication of Trypanosoma cruzi within the placental chorionic villi and are associated with the level of infection via the signaling pathway NF-κB.},
journal = {American journal of reproductive immunology (New York, N.Y. : 1989)},
volume = {90},
number = {4},
pages = {e13777},
doi = {10.1111/aji.13777},
pmid = {37766400},
issn = {1600-0897},
support = {(2018-2021)33620180100527CB//SECyT-Universidad Nacional de Córdoba/ ; 2020-2022RES2020.415//Universidad Nacional de Villa María/ ; 2015-0074//ANPCyT-PICT/ ; 2021-GRF-TII00352//ANPCyT-PICT/ ; },
abstract = {PROBLEM: Congenital Trypanosoma cruzi (T. cruzi) infection has been associated with changes in the levels of TNF-α and IFN-γ during the pregnancy. Therefore, we propose to study the participation and dynamics of proinflammatory cytokines in the infection process of placental explants infected by T. cruzi in vitro.

METHOD OF STUDY: Chorionic villous explants (CVE) obtained of human term placentas (n = 8) from normal pregnancies were cultured with 10[5] trypomastigotes/mL of Tulahuen strain DTU VI for 0, 2, 4, 16, 24, 48 and 72 h. Explants were treated with sulfasalazine (SULF) (5 mM) and N-acetyl-cysteine (NAC) (15 mM), as inhibitors molecules of NF-κB pathway, or LPS (1 μg/mL) for 24 and 72 h p.i. Motile trypomastigotes were counted in culture supernatants. Immunohistochemistry and ELISA for TNF-α, IFN-γ, IL-1β, IL-4, and IL-10 were performed in CVE and culture supernatants respectively. The parasite load was measured by RT-qPCR.

RESULTS: T. cruzi invades the chorionic villi from 4 h p.i. increasing significantly its DNA at 48 and 72 h p.i. of culture (parasite multiplication phase). They were detected in stromal cells, which was related to elevation of TNF-α, IL-1β, IFN-γ, and IL-10. The inhibition of NF-κB activity in the explants decreased the production of the analyzed cytokines, showing elevated levels of T. cruzi DNA during the multiplication phase of the parasite.

CONCLUSIONS: Placental tissue modifies the secretion of pro-inflammatory cytokines during the phase of parasite multiplication, but not during the invasion phase, which in turns modifies the level of infection via the signaling pathway NF-κB.},
}

@article {pmid37762548,
year = {2023},
author = {Chen, JS and Chiu, SC and Huang, SY and Chang, SF and Liao, KF},
title = {Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines.},
journal = {International journal of molecular sciences},
volume = {24},
number = {18},
pages = {},
doi = {10.3390/ijms241814246},
pmid = {37762548},
issn = {1422-0067},
support = {TCMF-A 108-014//Buddhist Tzu Chi Medical Foundation/ ; TTCRD110-21//Buddhist Tzu Chi Medical Foundation/ ; TTCRD110-31//Buddhist Tzu Chi Medical Foundation/ ; TTCRD111-33//Buddhist Tzu Chi Medical Foundation/ ; },
abstract = {Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit anti-proliferative and anti-metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p-cdc2, and p-cdc25c and up-regulating the expression of p21. In addition, ILL induced mitochondria-associated apoptosis through the up-regulation of cleaved -caspase-9 and -3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.},
}

@article {pmid37761021,
year = {2023},
author = {Ahmad, IM and Dafferner, AJ and Salloom, RJ and Abdalla, MY},
title = {Heme Oxygenase-1 Inhibition Modulates Autophagy and Augments Arsenic Trioxide Cytotoxicity in Pancreatic Cancer Cells.},
journal = {Biomedicines},
volume = {11},
number = {9},
pages = {},
doi = {10.3390/biomedicines11092580},
pmid = {37761021},
issn = {2227-9059},
abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form, accounting for more than 90% of all pancreatic malignancies. In a previous study, we found that hypoxia and chemotherapy induced expression of Heme Oxygenase-1 (HO-1) in PDAC cells and tissues. Arsenic trioxide (ATO) is the first-line chemotherapeutic drug for acute promyelocytic leukemia (APL). ATO increases the generation of reactive oxidative species (ROS) and induces apoptosis in treated cells. The clinical use of ATO for solid tumors is limited due to severe systemic toxicity. In order to reduce cytotoxic side effects and resistance and improve efficacy, it has become increasingly common to use combination therapies to treat cancers. In this study, we used ATO-sensitive and less sensitive PDAC cell lines to test the effect of combining HO-1 inhibitors (SnPP and ZnPP) with ATO on HO-1 expression, cell survival, and other parameters. Our results show that ATO significantly induced the expression of HO-1 in different PDAC cells through the p38 MAPK signaling pathway. ROS production was confirmed using the oxygen-sensitive probes DCFH and DHE, N-acetyl cysteine (NAC), an ROS scavenger, and oxidized glutathione levels (GSSG). Both ATO and HO-1 inhibitors reduced PDAC cell survival. In combined treatment, inhibiting HO-1 significantly increased ATO cytotoxicity, disrupted the GSH cycle, and induced apoptosis as measured using flow cytometry. ATO and HO-1 inhibition modulated autophagy as shown by increased expression of autophagy markers ATG5, p62, and LC3B in PDAC cells. This increase was attenuated by NAC treatment, indicating that autophagy modulation was through an ROS-dependent mechanism. In conclusion, our work explored new strategies that could lead to the development of less toxic and more effective therapies against PDAC by combining increased cellular stress and targeting autophagy.},
}

@article {pmid37760016,
year = {2023},
author = {Mokra, D and Mokry, J and Barosova, R and Hanusrichterova, J},
title = {Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {9},
pages = {},
doi = {10.3390/antiox12091713},
pmid = {37760016},
issn = {2076-3921},
support = {APVV-15_0075//Slovak Research and Development Agency/ ; APVV-18-0084//Slovak Research and Development Agency/ ; APVV-22-0342//Slovak Research and Development Agency/ ; VEGA 1/0131/22//VEGA/ ; VEGA 1/0093/22//VEGA/ ; },
abstract = {N-acetylcysteine (NAC) is widely used because of its mucolytic effects, taking part in the therapeutic protocols of cystic fibrosis. NAC is also administered as an antidote in acetaminophen (paracetamol) overdosing. Thanks to its wide antioxidative and anti-inflammatory effects, NAC may also be of benefit in other chronic inflammatory and fibrotizing respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, idiopathic lung fibrosis, or lung silicosis. In addition, NAC exerts low toxicity and rare adverse effects even in combination with other treatments, and it is cheap and easily accessible. This article brings a review of information on the mechanisms of inflammation and oxidative stress in selected chronic respiratory diseases and discusses the use of NAC in these disorders.},
}

@article {pmid37746996,
year = {2023},
author = {Abushanab, D and Gasim, M and Devi, D and Elbdairy, M and Elqasass, H and Ahmed, N and Vincent, M and Abdul Rouf, PV and Mohammed, HR and Hail, MA and Thomas, B and Elkassem, W and Hanssens, Y and Elgassim, M and Elmoheen, A and Azad, A and Mohammed, S and Salem, W},
title = {Patterns and outcomes of paracetamol poisoning management in Hamad Medical Corporation, Qatar: A retrospective cohort study.},
journal = {Medicine},
volume = {102},
number = {38},
pages = {e34872},
pmid = {37746996},
issn = {1536-5964},
mesh = {Young Adult ; Humans ; Adolescent ; Adult ; Qatar/epidemiology ; Acetaminophen ; Retrospective Studies ; *Drug-Related Side Effects and Adverse Reactions ; *Drug Overdose/therapy ; Acetylcysteine/therapeutic use ; },
abstract = {We aimed to investigate the characteristics and clinical outcomes of paracetamol poisoning and paracetamol overdose in Qatar. This retrospective cohort study included patients admitted to the emergency department (ED). We included patients who presented with excessive paracetamol ingestion, between December 2018 and September 2019. The primary outcomes were describing the characteristics and outcomes of paracetamol overdose (from a suicidal overdose or accidental overdose, dose ≤ 150 mg/kg, when serum levels of <60 mmol/L) or dose ingested (≤75 mg/kg) with staggered ingestion poisoning due to suicidal attempt or accidental attempt, defined as the dose ingested (>150 mg/kg), acute ingestion, nomogram level more than the treatment line, or dose ingested (>75 mg/kg) with staggered ingestion, and assessing the management of excessive paracetamol ingestion. Secondary outcomes included evaluation of the time difference between ingestion and time of administration, hospitalization, and adverse drug events. Significant differences were detected between patients who presented with paracetamol overdose and those who presented with paracetamol toxicity. A total of 69 patients were analyzed, of whom 43 received paracetamol overdose (mean age 27.5 ± 11.1 years) and 26 had paracetamol poisoning (mean age 25 ± 6.22 years). Paracetamol poisoning was identified in 26% of the patients with a 24.3% history of psychiatric illness, compared to 18.6% with paracetamol overdose. More patients presented with paracetamol toxicity in the time between ingestion and obtaining serum levels compared to the overdose group. A significantly longer length of hospitalization was observed in the toxicity group. A significantly higher number of patients in the toxicity group received N-acetylcysteine (NAC). More hypotension and rashes were observed among those who received NAC in the toxicity group. Patients presenting to the ED due to paracetamol toxicity are not uncommon, and most cases occur in young adults, and few in patients with a history of psychiatric illness, suggesting that preventive approaches are highly required.},
}

Young Adult
Humans
Adolescent
Adult
Qatar/epidemiology
Acetaminophen
Retrospective Studies
*Drug-Related Side Effects and Adverse Reactions
*Drug Overdose/therapy
Acetylcysteine/therapeutic use

@article {pmid37742933,
year = {2023},
author = {Zhuang, J and Yuan, Q and Chen, C and Liu, G and Zhong, Z and Zhu, K and Guo, J},
title = {Nanosecond pulsed cold atmospheric plasma jet suppresses proliferation and migration of human glioblastoma cells via apoptosis promotion and EMT inhibition.},
journal = {Archives of biochemistry and biophysics},
volume = {},
number = {},
pages = {109757},
doi = {10.1016/j.abb.2023.109757},
pmid = {37742933},
issn = {1096-0384},
abstract = {Glioblastoma (GBM) is one of the most aggressive and challenging cancers to treat. Despite extensive research on dozens of cancer cells, including GBM, the effect of cold atmospheric plasma (CAP) on the invasive migration of GBM cells has received limited attention, and the underlying mechanisms remain poorly understood. This study aims to investigate the potential molecular mechanism of ns-CAPJ in inhibiting the invasive migration of human GBM cells. The findings indicate that ns-CAPJ significantly reduces GBM cell invasion and migration, and induces apoptosis in GBM cells. Further mechanistic studies demonstrate a direct correlation between the suppression of the epithelial-mesenchymal transition (EMT) signaling pathway and ns-CAPJ's inhibitory effect on GBM cell invasion and migration. Additionally, combined with the N-acetyl cysteine (NAC, a ROS inhibitor) assay, we found that the ROS stimulated by the ns-CAPJ plays an important role in suppressing the EMT process. This work is expected to provide new insight into understanding the molecular mechanisms of how ns-CAPJ inhibits the proliferation and migration of human GBM cells.},
}

@article {pmid37714033,
year = {2023},
author = {Ma, R and Sun, T and Wang, X and Ren, K and Min, T and Xie, X and Wang, D and Li, K and Zhang, Y and Zhu, K and Mo, C and Dang, C and Yang, Y and Zhang, H},
title = {Chronic exposure to low-dose deltamethrin can lead to colon tissue injury through PRDX1 inactivation-induced mitochondrial oxidative stress injury and gut microbial dysbiosis.},
journal = {Ecotoxicology and environmental safety},
volume = {264},
number = {},
pages = {115475},
doi = {10.1016/j.ecoenv.2023.115475},
pmid = {37714033},
issn = {1090-2414},
mesh = {Humans ; Animals ; Mice ; Dysbiosis/chemically induced ; *Gastrointestinal Microbiome ; Colon ; Oxidative Stress ; Acetylcysteine ; *Coleoptera ; Peroxiredoxins/genetics ; },
abstract = {OBJECTIVE: To date, it is unclear whether deltamethrin (DLM) intake causes damage to colon tissue. Hence, in this study, we aimed to clarify the effect of long-term exposure to low-dose DLM on colon tissues, and its potential mechanisms.

METHODS: Mice were treated with DLM (0.2 mg/kg/day) or DLM combined with N-acetyl-l-cysteine (NAC) (50 mg/kg/day) for 8 weeks. Human colon cancer cells (HCT-116) were treated with DLM (0, 25, 50, or 100 µM), NAC (2 mM), or overexpression plasmids targeting peroxiredoxin 1 (PRDX1) for 48 h. DLM was detected using a DLM rapid detection card. Colon injury was evaluated using haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was determined using immunofluorescence staining (IF), western blotting (WB) and flow cytometry (FC) assays. MitoTracker, JC-1, and glutathione (GSH) detection were used to detect mitochondrial oxidative stress. Intestinal flora were identified by 16 S rDNA sequencing.

RESULTS: DLM accumulation was detected in the colon tissue and faeces of mice following long-term intragastric administration. Interestingly, our results showed that, even at a low dose, long-term intake of DLM resulted in severe weight loss and decreased the disease activity index scores and colon length. The results of IF, WB, and FC showed that DLM induced apoptosis in the colon tissue and cells. MitoTracker, JC-1, and GSH assays showed that DLM increased mitochondrial stress in colonic epithelial cells. Mechanistic studies have shown that increased mitochondrial stress and apoptosis are mediated by PRDX1 inhibition. Further experiments showed that PRDX1 overexpression significantly reduced DLM-induced oxidative stress injury and apoptosis. In addition, we observed that chronic exposure to DLM altered the composition of the intestinal flora in mice, including an increase in Odoribacter and Bacteroides and a decrease in Lactobacillus. The gut microbial richness decreased after DLM exposure in mice. Supplementation with NAC both in vivo and in vitro alleviated DLM-induced oxidative stress injury, colonic epithelial cell apoptosis, and gut microbial dysbiosis.

CONCLUSION: Chronic exposure to DLM, even at small doses, can cause damage to the colon tissue, which cannot be ignored. The production and use of pesticides such as DLM should be strictly regulated during agricultural production.},
}

Humans
Animals
Mice
Dysbiosis/chemically induced
*Gastrointestinal Microbiome
Colon
Oxidative Stress
Acetylcysteine
*Coleoptera
Peroxiredoxins/genetics

@article {pmid37742495,
year = {2023},
author = {Zeng, Y and Yang, Q and Ouyang, Y and Lou, Y and Cui, H and Deng, H and Zhu, Y and Geng, Y and Ouyang, P and Chen, L and Zuo, Z and Fang, J and Guo, H},
title = {Nickel induces blood-testis barrier damage through ROS-mediated p38 MAPK pathways in mice.},
journal = {Redox biology},
volume = {67},
number = {},
pages = {102886},
doi = {10.1016/j.redox.2023.102886},
pmid = {37742495},
issn = {2213-2317},
abstract = {Nickel (Ni) is an essential common environmental contaminant, it is hazardous to male reproduction, but the precise mechanisms are still unknown. Blood-testis barrier (BTB), an important testicular structure consisting of connections between sertoli cells, is the target of reproductive toxicity caused by many environmental toxins. In this study, ultrastructure observation and BTB integrity assay results indicated that NiCl2 induced BTB damage. Meanwhile, BTB-related proteins including the tight junction (TJ), adhesion junction (AJ) and the gap junction (GJ) protein expression in mouse testes as well as in sertoli cells (TM4) were significantly decreased after NiCl2 treatment. Next, the antioxidant N-acetylcysteine (NAC) was co-treated with NiCl2 to study the function of oxidative stress in NiCl2-mediated BTB deterioration. The results showed that NAC attenuated testicular histopathological damage, and the expression of BTB-related proteins were markedly reversed by NAC co-treatment in vitro and vivo. Otherwise, NiCl2 activated the p38 MAPK signaling pathway. And, NAC co-treatment could significantly inhibit p38 activation induced by NiCl2 in TM4 cells. Furthermore, in order to confirm the role of the p38 MAPK signaling pathway in NiCl2-induced BTB impairment, a p38 inhibitor (SB203580) was co-treated with NiCl2 in TM4 cells, and p38 MAPK signaling inhibition significantly restored BTB damage induced by NiCl2 in TM4 cells. These results suggest that NiCl2 treatment destroys the BTB, in which the oxidative stress-mediated p38 MAPK signaling pathway plays a vital role.},
}

@article {pmid37741428,
year = {2023},
author = {Araujo, AM and Cerqueira, SVS and Menezes-Filho, JER and Heimfarth, L and Matos, KKOG and Mota, KO and Conceição, MRL and Marques, LP and Roman-Campos, D and Santos-Neto, AGD and Albuquerque-Júnior, RLC and Santos, VCO and Vasconcelos, CML},
title = {Naringin improves post-ischemic myocardial injury by activation of KATP channels.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {176069},
doi = {10.1016/j.ejphar.2023.176069},
pmid = {37741428},
issn = {1879-0712},
abstract = {Naringin (NRG) is a flavonoid with recognized cardioprotective effects. Then, it was investigated the cardioprotective mechanisms of NRG against ischemia-reperfusion (I/R) injury. The rats were pretreated for 7 days (v.o.) with NRG (25 mg/kg) or n-acetylcysteine (NAC, 100 mg/kg) and their isolated hearts were subjected to global ischemia (30 min) and reperfusion (60 min). Furthermore, isolated hearts were perfused with 5 μM NRG in the presence of 10 μM glibenclamide (GLI) and subjected to I/R protocol. In healthy ventricular cardiomyocyte, it was evaluated the acute effect of 5 μM NRG on the GLI sensitive current. The results showed that NRG pretreatment restored the cardiac function and electrocardiogram (ECG) alterations induced by I/R injury, decreasing arrhythmia scores and the occurrence of severe arrhythmias. Lactate dehydrogenase and infarct area were decreased while superoxide dismutase (SOD), catalase and citrate synthase activities increased. Expression of SOD CuZn and SOD Mn not was altered. NRG treatment decreased reactive oxygen species (ROS) generation and lipid peroxidation without alter sulfhydryl groups and protein carbonylation. Also, NRG (5 μM) increased the glibenclamide sensitive current in isolated cardiomyocytes. In isolated heart, the cardioprotection of NRG was significantly reduced by GLI. Furthermore, NRG promoted downregulation of Bax expression and Bax/Bcl-2. Histopathological analysis showed that NRG decreased cell edema, cardiomyocytes and nucleus diameter. Thus, NRG has a cardioprotective effect against cardiac I/R injury which is mediated by its antioxidant and antiapoptotic actions and KATP channels activation.},
}

@article {pmid37741051,
year = {2023},
author = {Fayyazi, F and Ebrahimi, V and Mamaghani, MM and Abgharmi, BA and Zarrini, G and Mosarrezaii, A and Charkhian, H and Gholinejad, Z},
title = {N-Acetyl cysteine amide and cerium oxide nanoparticles as a drug delivery for ischemic stroke treatment: Inflammation and oxidative stress crosstalk.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {80},
number = {},
pages = {127300},
doi = {10.1016/j.jtemb.2023.127300},
pmid = {37741051},
issn = {1878-3252},
abstract = {BACKGROUND: Inflammation and oxidative stress crosstalk is involved in the ischemic stroke(IS) pathogenesis and the new therapeutic options should be offered based on the targets that are critical in the golden hour of IS. YKL-40 and total antioxidant capacity(TAC), the inflammation and oxidative stress biomarkers, provide us with clues for proper intervention targets. N-acetyl cysteine amide (NACA), a lipophilic antioxidant, with a nanoparticle-based drug delivery system is permeable enough to penetrate blood-brain barrier (BBB) and was proposed as a new treatment option for IS. In this study, we evaluated the YKL-40 and TAC levels in the sera of IS patients to elucidate the best intervention target. A rat tissue model is used to assess the NACA efficiency. The microbiology tests performed to figure out the potential NACA and antibiotics interactions.

MATERIAL AND METHODS: The YKL-40 and TAC were measured in the serum of IS patients by ELISA and FRAP methods, respectively. The serum samples were obtained 12 h after the patient's admission and meantime other laboratory findings and NIHSS-based prognosis were recorded. In the animal study, the brain cortex, liver, kidney, adipose, and the heart of healthy rats were dissected and then incubated in DMEM cell culture media containing 50 micrograms/milliliter of nanoparticles; the nanoparticles were titanium dioxide nanoparticles (TiO2 NPs), copper oxide nanoparticles (CuO NPs) and cerium dioxide nanoparticles (CeO2 NPs). Olive oil and human serum albumin solution were exposed to the nanoparticles with and without NACA. TAC was measured in the supernatant culture media. With similar concentrations and settings, we evaluated the NACA, nanoparticle, and antibiotics interactions on pseudomonas aeruginosa.

RESULTS: There was a nonparametric correlation between YKL-40 levels and post stroke serum TAC levels. Nonsmokers had higher YKL-40 and TAC levels than smokers. A new calculated variable, urea*lymphocyte/age, predicts a poor prognosis with an acceptable AUC (0.708). Exposing to the nanoparticles, the liver, kidney, and brain had a significantly higher TAC than adipose and cardiac tissue. The NACA had an ameliorative effect against TiO2 NPs in the brain. This effectiveness of NACA was also observed against CuO NPs treatment. However, the CeO2 NPs exert a strong antioxidant property by reducing the TAC in the brain tissue but not the others. Albumin showed antioxidant properties by itself, but olive oil had an inert behavior. NACA had no interaction with the action of routine antibiotics.

CONCLUSION: Oxidative stress but not inflammation is the best point for intervention in IS patients because YKL-40 has not a relationship with NIHSS score. The CeO2 NPs and NACA combination are eligible option to develop antioxidant-based drug for the treatment of IS. As a complementary finding, the urea*lymphocyte/age is proposed as a NIHSS-based prognosis biomarker.},
}

@article {pmid37739116,
year = {2023},
author = {Mushtaq, I and Mushtaq, I and Akhlaq, A and Usman, S and Ishtiaq, A and Khan, M and Mustafa, G and Khan, MS and Arooj, I and Bibi, S and Liaqat, F and Akhtar, Z and Murtaza, I},
title = {Cardioprotective effect of tetra(aniline) containing terpolymers through miR-15a-5p and MFN-2 regulation against hypertrophic responses.},
journal = {Archives of biochemistry and biophysics},
volume = {},
number = {},
pages = {109763},
doi = {10.1016/j.abb.2023.109763},
pmid = {37739116},
issn = {1096-0384},
abstract = {OBJECTIVE: Cardiac hypertrophy is a condition of abnormal cardiomyocyte enlargement accompanied by ventricular wall thickening. The study aims to investigate the role of miR-15a-5p in the regulation of mitofusin-2 (MFN-2) and to explore the cardioprotective effect of terpolymers ES-37 and L-37.

METHODS: In this study, the Sprague Dawley rats' cardiac hypertrophic model was established by administering 5 mg/kg Isoproterenol subcutaneously every other day for 14 days. As treatment rats received NAC (50 mg/kg), NAC treatment (50 mg/kg NAC + 5 mg/kg ISO), ES-37 (1 mg/kg) and ES-37 treatment (1 mg/kg ES-37+5 mg/kg ISO), L-37 (1 mg/kg) and L-37 treatment (1 mg/kg L-37+5 mg/kg ISO). subcutaneously every other day for 14 days. NAC, ES 37 and L-37 were given after 1 h of Isoproterenol administration in treatment groups. Cardiac hypertrophy was confirmed through morphological and histological analysis. For estimation of oxidative stress profiling, ROS and TBARS and antioxidative profiling superoxide dismutase (SOD), Catalase, and Glutathione (GSH) levels were checked. Triglyceride, cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) were performed to evaluate levels of lipid profiling and liver profiling. Molecular expression analysis was checked through real-time PCR, and western blotting both at the transcriptional and translational levels. Molecular docking studies were performed to study the interactions and modes of binding between the synthetic polymers with three proteins (Mitofusin-2, DRP-1 and PUMA). All the studies were carried out using the AutoDock Vina software and the protein-ligand complexes were visualized in Biovia Discovery Studio.

RESULTS: Cardiac hypertrophy was confirmed by the relative changes in the cellular structure of the heart by histopathological examination and physiological changes by estimating organ weights. Biochemical profiling results depict elevated oxidative and lipid profiles signify myocardial damage. N-acetyl cysteine (NAC), ES-37, and L-37 overcome the cardiac hypertrophic responses through attenuating oxidative stress and enhancing the antioxidative signaling mechanism. miR-15a-5p was identified as hypertrophic microRNA directly regulating the expression of Mitofusion-2 (MFN-2). Significantly increased expression of miR-15a-5p, Dynamin related protein 1 (Drp1), and P53 upregulated modulator of apoptosis (PUMA), was observed in the disease group, whereas MFN-2 expression was observed downregulated. N-acetyl cysteine (NAC), ES-37, and L-37 showed increased expression of antiapoptotic maker MFN-2 and decreased expression of miR-15a-5p, Drp1, and PUMA in treatment groups suggesting their cardioprotective role in attenuation of cardiac hypertrophy. An analysis of the docking results shows that ES-37 has greater binding affinity with the target proteins compared to L-37, with the highest binding values reported for MFN-2.

CONCLUSION: The physiochemical properties of ES-37 and L-37 predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS. Molecular docking results shows that the polymer ES-37 has greater binding affinity with the target proteins compared to L-37, with the highest binding values reported for MFN-2. Thus, the study validates the role and targeting of miR-15a-5p and MFN-2 in cardiac hypertrophy as well as the therapeutic potential of NAC, ES-37, and LS-37 in overcoming oxidative stress and myocardial damage.},
}

@article {pmid37499713,
year = {2023},
author = {He, D and Qian, L and Chen, X and He, B and Li, J},
title = {Durable cellulose paper by grafting thiol groups and controlling silver deposition for ultrahigh electromagnetic interference shielding.},
journal = {International journal of biological macromolecules},
volume = {248},
number = {},
pages = {125972},
doi = {10.1016/j.ijbiomac.2023.125972},
pmid = {37499713},
issn = {1879-0003},
mesh = {*Ammonia ; *Silver ; Acetylcysteine ; Cellulose ; Electric Conductivity ; Sulfhydryl Compounds ; },
abstract = {Electromagnetic interference (EMI) shielding paper with durability and high effectiveness is of significant importance to long-term service for preventing EMI pollution. Herein, we report a practical method for preparing cellulose paper/Ag composite with outstanding durable and ultrahigh EMI shielding performance by electroless silver plating. The silver deposition process, the surface morphology, the silver content and conductivity of the composite can be controlled by varying the amount of N-acetyl-L-cysteine (NAC) grafted onto the cellulose fibers and ammonia amount for silver-ammonia complex formation. Moreover, the grafted NAC with thiol groups on cellulose can enhance the adhesion between silver and cellulose paper, meanwhile, NAC as the reducing agent can result in a more complete flower-shaped silver structure and reducing the reflection of electromagnetic waves in silver layer. The composite exhibited excellent conductivity, EMI shielding effectiveness (SE) up to 106 dB and outstanding durability. After 10,000 bending times and 60 abrasion cycles respectively, the electrical resistance of the composite only increased from 0.030 Ω/sq. to 0.041 Ω/sq. and 0.050 Ω/sq., and the EMI SE decreased to 102 dB and 105 dB.},
}

*Ammonia
*Silver
Acetylcysteine
Cellulose
Electric Conductivity
Sulfhydryl Compounds

@article {pmid37732506,
year = {2023},
author = {Sharma, S and Sharma, V and Taneja, S and Alka Bhatia, and Anand, A and Patil, AN and Banerjee, D},
title = {Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.},
journal = {Journal of complementary & integrative medicine},
volume = {},
number = {},
pages = {},
pmid = {37732506},
issn = {1553-3840},
abstract = {OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any.

METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination.

RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis.

CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.},
}

@article {pmid37730076,
year = {2023},
author = {Zhou, X and Chen, Q and Chen, L and Liao, X and Wang, Z and Zhu, F},
title = {The effect of reactive oxygen species (ROS) in immunity and WSSV infection of Scylla paramamosain.},
journal = {Fish & shellfish immunology},
volume = {},
number = {},
pages = {109075},
doi = {10.1016/j.fsi.2023.109075},
pmid = {37730076},
issn = {1095-9947},
abstract = {Reactive oxygen species (ROS) are typically regarded as being generated by the cellular respiratory chain or by cells under pathological damage, which play a crucial role as signaling molecules in promoting hemocytes circulation and normal cellular physiological functions. In this study, the antioxidant N-acetylcysteine (NAC) was used to reduce ROS in vivo and in vitro, which to analyze the effect of ROS on innate immunity and viral infection of mud crab. The total hemocyte count (THC), phenoloxidase (PO), superoxide dismutase (SOD) activity, immune-relative genes were analyzed, respectively. Moreover, the effect of ROS on WSSV infection was analyzed by THC and hemocytes apoptosis. The data showed that NAC could effectively remove and inhibit intracellular ROS. The THC of NAC group was reduced at 12 h and 24 h compared with that of control. And the inhibition of ROS by NAC could increase the SOD activity with control group, while increased the PO activity caused by early WSSV infection. And NAC could up-regulate the expression of MCM7, JAK, TLR and proPO significantly, while down-regulate the expression of Astakine, proPO, caspase and p53. Similarly, NAC could inhibit WSSV-induced apoptosis of S. paramamosain hemocytes. The data illustrated that ROS participates in the interaction between hemocytes and virus infection by regulating innate immunity. Especially, after NAC inhibited ROS, the expression of hemocytes proliferation gene Astakine was also inhibited, which may indicate that ROS is related to the process of hemocytes proliferation. The data will show a preliminary exploration on the regulatory role of ROS in crustacean immune system.},
}

@article {pmid37726091,
year = {2023},
author = {Sun, Z and Wu, K and Feng, C and Lei, XG},
title = {Selenium-dependent glutathione peroxidase 1 regulates transcription of elongase 3 in murine tissues.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2023.09.010},
pmid = {37726091},
issn = {1873-4596},
abstract = {We have previously shown dysregulated lipid metabolism in tissues of glutathione peroxidase 1 (GPX1) overexpressing (OE) or deficient (KO) mice. This study explored underlying mechanisms of GPX1 in regulating tissue fatty acid (FA) biosynthesis. GPX1 OE, KO, and wild-type (WT) mice (n = 5, male, 3-6 months old) were fed a Se-adequate diet (0.3 mg/kg) and assayed for liver and adipose tissue FA profiles and mRNA levels of key enzymes of FA biosynthesis and redox-responsive transcriptional factors (TFs). These three genotypes of mice (n = 5) were injected intraperitoneally with diquat, ebselen, and N-acetylcysteine (NAC) at 10, 50, and 50 mg/kg of body weight, respectively, and killed at 0 and 12 h after the injections to detect mRNA levels of FA elongases and desaturases and the TFs in the liver and adipose tissue. A luciferase reporter assay with targeted deletions of mouse Elovl3 promoter was performed to determine transcriptional regulations of the gene by GPX1 mimic ebselen in HEK293T cells. Compared with WT, GPX1 OE and KO mice had 9-42% lower (p < 0.05) and 36-161% higher (p < 0.05) concentrations of C20:0, C22:0, and C24:0 in these two tissues, respectively, along with reciprocal increases and decreases (p < 0.05) of Elovl3 transcripts. Ebselen and NAC decreased (p < 0.05), whereas diquat decreased (p < 0.05), Elovl3 transcripts in the two tissues. Overexpression and knockout of GPX1 decreased (p < 0.05) and increased (p < 0.05) ELOVL3 levels in the two tissues, respectively. Three TFs (GABP, SP1, and DBP) were identified to bind the Elovl3 promoter (-1164/+33 base pairs). Deletion of DBP (-98/-86 base pairs) binding domain in the promoter attenuated (13%, p < 0.05) inhibition of ebselen on Elovl3 promoter activation. In summary, GPX1 overexpression down-regulated very long-chain FA biosynthesis via transcriptional inhibition of the Elovl3 promoter activation.},
}

@article {pmid37715092,
year = {2023},
author = {Peng, HX and Chai, F and Chen, KH and Huang, YX and Wei, GJ and Yuan, H and Pang, YF and Luo, SH and Wang, CF and Chen, WC},
title = {Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {37715092},
issn = {1559-0720},
support = {2020KY13017//Guangxi University Young and Middle-aged Teachers' Basic Ability Improvement Project/ ; GZZC2020248//Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Self-financing Scientific Research Project/ ; Z20201416//Guangxi Zhuang Autonomous Region Health and Health Commission Self-financing Scientific Research Course/ ; 81960303//National Natural Science Foundation of China/ ; 2020GXNSFAA297257)//Guangxi Natural Science Foundation Project/ ; },
abstract = {Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.},
}

@article {pmid37712506,
year = {2023},
author = {Zhang, Q and Liu, Z and Wang, T and Yu, M and Li, X},
title = {Efficacy and acceptability of adjunctive n-acetylcysteine for psychotic disorders: Systematic review and meta-analysis.},
journal = {Human psychopharmacology},
volume = {},
number = {},
pages = {e2880},
doi = {10.1002/hup.2880},
pmid = {37712506},
issn = {1099-1077},
abstract = {INTRODUCTION: N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders.

METHODS: PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop-out rates.

RESULTS: A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24 weeks and >24 weeks). There was also no statistical difference in drop-out rates between the two groups.

CONCLUSION: For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.},
}

@article {pmid37711440,
year = {2023},
author = {Yamamoto, T and Tanji, M and Mitsunaga, F and Nakamura, S},
title = {SARS-CoV-2 sublingual vaccine with RBD antigen and poly(I:C) adjuvant: Preclinical study in cynomolgus macaques.},
journal = {Biology methods & protocols},
volume = {8},
number = {1},
pages = {bpad017},
doi = {10.1093/biomethods/bpad017},
pmid = {37711440},
issn = {2396-8923},
abstract = {Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals: control [just 400 µg poly(I:C) per head], low dose [30 µg RBD and 400 µg poly(I:C) per head], and high dose [150 µg RBD and 400 µg poly(I:C) per head], respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.},
}

@article {pmid37710183,
year = {2023},
author = {Du, YX and Zhao, YT and Sun, YX and Xu, AH},
title = {Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {29},
number = {1},
pages = {125},
pmid = {37710183},
issn = {1528-3658},
support = {XJ2023000701//cultivating scientific research project of the Second Hospital of Dalian Medical University/ ; 2211004//Dalian Medical Science Research Program Project/ ; },
abstract = {BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP.

METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues.

RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model.

CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.},
}

@article {pmid37705917,
year = {2023},
author = {Granata, S and Bruschi, M and Verlato, A and Pontrelli, P and Gesualdo, L and Stallone, G and Zaza, G},
title = {Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients.},
journal = {Kidney international reports},
volume = {8},
number = {9},
pages = {1852-1863},
doi = {10.1016/j.ekir.2023.06.017},
pmid = {37705917},
issn = {2468-0249},
abstract = {INTRODUCTION: The complete systemic deregulated biological network in patients on peritoneal dialysis (PD) is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition.

METHODS: We applied an innovative bioinformatic analysis of gene expression microarray data (mainly based on support vector machine (SVM) learning) to compare the transcriptomic profile of peripheral blood mononuclear cells (PBMCs) of healthy subjects (HS), chronic kidney disease (CKD) patients, and patients on PD divided into a microarray group (5 HS, 9 CKD, and 10 PD) and a validation group (10 HS, 15 CKD, and 15 PD). Classical well-standardized biomolecular approaches (western blotting and flow cytometry) were used to validate the transcriptomic results.

RESULTS: Bioinformatics revealed a distinctive PBMC transcriptomic profiling for PD versus CKD and HS (n = 419 genes). Transcripts encoding for key elements of the autophagic pathway were significantly upregulated in PD, and the autophagy related 5 (ATG5) reached the top level of discrimination [-Log10 P-value = 11.3, variable importance in projection (VIP) score = 4.8, SVM rank:1]. Protein levels of ATG5 and microtubule associated protein 1 light chain 3 beta (LC3B), an important constituent of the autophagosome, validated microarray results. In addition, the incubation of PBMCs of HS with serum of patients on PD upregulated both proteins. Autophagy in PBMCs from patients on PD was attenuated by N-acetyl-cysteine or Resatorvid treatment.

CONCLUSIONS: Our data demonstrated, for the first time, that the autophagy pathway is activated in immune-cells of patients on PD, and this may represent a novel therapeutic target.},
}

@article {pmid37705749,
year = {2023},
author = {Wang, L and Huang, B and Zeng, Y and Yang, J and Li, Z and Ng, JPL and Xu, X and Su, L and Yun, X and Qu, L and Chen, R and Luo, W and Wang, Y and Chen, C and Yang, L and Qu, Y and Zhang, W and Chan, JTW and Wang, X and Law, BYK and Mok, SWF and Chung, SK and Wong, VKW},
title = {N-Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model.},
journal = {International journal of biological sciences},
volume = {19},
number = {13},
pages = {4082-4102},
doi = {10.7150/ijbs.85028},
pmid = {37705749},
issn = {1449-2288},
abstract = {Epalrestat, an aldose reductase inhibitor (ARI), has been clinically adopted in treating diabetic neuropathy in China and Japan. Apart from the involvement in diabetic complications, AR has been implicated in inflammation. Here, we seek to investigate the feasibility of clinically approved ARI, epalrestat, for the treatment of rheumatoid arthritis (RA). The mRNA level of AR was markedly upregulated in the peripheral blood mononuclear cells (PBMCs) of RA patients when compared to those of healthy donors. Besides, the disease activity of RA patients is positively correlated with AR expression. Epalrestat significantly suppressed lipopolysaccharide (LPS) induced TNF-α, IL-1β, and IL-6 in the human RA fibroblast-like synoviocytes (RAFLSs). Unexpectedly, epalrestat treatment alone markedly exaggerated the disease severity in adjuvant induced arthritic (AIA) rats with elevated Th17 cell proportion and increased inflammatory markers, probably resulting from the increased levels of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA). Interestingly, the combined treatment of epalrestat with N-Acetylcysteine (NAC), an anti-oxidant, to AIA rats dramatically suppressed the production of 4-HNE, MDA and inflammatory cytokines, and significantly improved the arthritic condition. Taken together, the anti-arthritic effect of epalrestat was diminished or even overridden by the excessive accumulation of toxic 4-HNE or other reactive aldehydes in AIA rats due to AR inhibition. Co-treatment with NAC significantly reversed epalrestat-induced upregulation of 4-HNE level and potentiated the anti-arthritic effect of epalrestat, suggesting that the combined therapy of epalrestat with NAC may sever as a potential approach in treating RA. Importantly, it could be regarded as a safe intervention for RA patients who need epalrestat for the treatment of diabetic complications.},
}

@article {pmid37705237,
year = {2023},
author = {Sheng, Y and Zhang, C and Cai, D and Xu, G and Chen, S and Li, W and Dong, J and Shen, B and Tang, J and Xu, L},
title = {2,2',4,4'-Tetrabromodiphenyl ether and cadmium co-exposure activates aryl hydrocarbon receptor pathway to induce ROS and GSDME-dependent pyroptosis in renal tubular epithelial cells.},
journal = {Environmental toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1002/tox.23957},
pmid = {37705237},
issn = {1522-7278},
support = {2023RC101//Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; 22206059//National Natural Science Foundation of China/ ; 2023R417A016//Zhejiang Provincial University Students Science and Technology Innovation Activity/ ; },
abstract = {We have previously found that a mixture exposure of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand-receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE-47 (50 μM) or Cd (5 μM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co-treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N-acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved-caspase-3 and gasdermin E N-terminal (GSDME-NT), while caspase-8, caspase-3, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE-47 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME-dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.},
}

@article {pmid37701655,
year = {2023},
author = {Eslami, G and Ghorbani, A and Akbari, J and Farmoudeh, A and Faghih, F and Moghimi, M},
title = {Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.},
journal = {Frontiers in dentistry},
volume = {20},
number = {},
pages = {18},
doi = {10.18502/fid.v20i18.12824},
pmid = {37701655},
issn = {2676-296X},
abstract = {Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.},
}

@article {pmid37696227,
year = {2023},
author = {Chan, CY and Conley, SF and Salameh, S and Sayegh, J and Wurzba, SDS and Grenier, K and Linn, DT and Partain, MP and Daniel, SJ},
title = {Otologic safety of intratympanic N-acetylcysteine in an animal model.},
journal = {International journal of pediatric otorhinolaryngology},
volume = {173},
number = {},
pages = {111702},
doi = {10.1016/j.ijporl.2023.111702},
pmid = {37696227},
issn = {1872-8464},
abstract = {OBJECTIVE: N-acetylcysteine (NAC) is an anti-oxidant and mucolytic effective against bacterial biofilms, making it useful in the treatment of chronically discharging ears that are unresponsive to traditional treatment methods. The objective of this study was to evaluate the otologic safety of intratympanic NAC combined with Ciprodex® in an animal model.

METHODS: Baseline distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) measurements were performed for both ears on thirteen guinea pigs from the animal care research facilities of the McGill University Health Center. This was followed by intratympanic administration of control solution (Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the left ear and experimental solution (1.25% NAC/Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the right ear. Three additional intratympanic injections were performed over the next fourteen days. DPOAE and ABR measurements were repeated 3-4 weeks after the initial procedure. Outcome measures included differences in DPOAE and ABR thresholds after intervention, clinical evidence of vestibular dysfunction and histological evidence of ototoxicity.

RESULTS: There were no significant differences in the ABR thresholds and DPOAE results of the control and experimental ears at baseline and after intervention. There was neither clinical manifestation of vestibular dysfunction nor histological evidence of ototoxicity.

CONCLUSION: Our study suggests that intratympanic 1.25% NAC with ciprofloxacin and dexamethasone is safe in guinea pigs and support its potential use in the treatment of chronically discharging ears. Further studies in humans are required to analyze its efficacy relative to conventional treatments.

LEVEL OF EVIDENCE: Animal Research.},
}

@article {pmid37692935,
year = {2023},
author = {Zhang, J and Xu, X and Liang, Y and Wu, X and Qian, Z and Zhang, L and Wang, T},
title = {Particulate matter promotes the epithelial to mesenchymal transition in human lung epithelial cells via the ROS pathway.},
journal = {American journal of translational research},
volume = {15},
number = {8},
pages = {5159-5167},
pmid = {37692935},
issn = {1943-8141},
abstract = {OBJECTS: Epidemiologic studies have linked exposure to airborne pollutant particulate matter (PM) with increased rates of chronic cardiopulmonary diseases, including asthma and idiopathic pulmonary fibrosis (IPF). Several investigations have suggested that the epithelial-to-mesenchymal transition (EMT) may contribute to the complex pathobiology of environmental exposure-mediated pulmonary fibrosis. The present study was designed to characterize the mechanisms of PM-mediated EMT in human lung epithelial cells (HBECs).

METHODS AND RESULTS: PM induced significant dose (0-100 μg/ml) and time (0-72 h)-dependent increases in transforming growth factor β (TGFβ) and fibronectin (FN) protein levels in HBECs lysates. PM-activated TGFβ and FN protein production in HBECs was prevented by the antioxidant N-acetyl-cysteine (NAC, 5 mM). Furthermore, the NF-κB inhibitor BAY11-7082 (5 μM) abolished PM-induced FN production in HBECs. Biomarkers of EMT (ACTA2, SNAIL1 and SNAIL2) in PM-treated HBECs were significantly increased at the mRNA level compared to control cells.

CONCLUSIONS: These results demonstrate that PM increases protein levels of TGFβ and FN via reactive oxygen species (ROS)-dependent pathways. In addition, PM exposure induces EMT in human lung epithelial cells, supporting a novel mechanism for PM-induced pulmonary fibrosis.},
}

@article {pmid37692924,
year = {2023},
author = {Zhang, J and Wu, X and Liang, Y and Kelly, G and Burt, JM and Zhang, L and Wang, T},
title = {Particulate matter increases connexin 43 expression and exacerbates endothelial barrier disruption.},
journal = {American journal of translational research},
volume = {15},
number = {8},
pages = {5099-5109},
pmid = {37692924},
issn = {1943-8141},
abstract = {OBJECTIVES: Particulate Matter (PM) air pollution is known to exacerbate cardiopulmonary diseases. We previously demonstrated that PM mediates endothelial injury and barrier disruption by modulating the endothelial cytoskeleton and cell-cell junctions, but the effects of PM exposure on cell-cell communication and gap junction activity are still unknown.

METHODS: This study focused on the characterization of PM-regulated endothelial dysfunction through connexin 43 (Cx43), the most abundant gap junction protein expressed in lung endothelial cells (ECs), using cultured human lung endothelial cells and a well-characterized PM sample.

RESULTS: PM exposure induced a time-dependent increase of Cx43 in human lung ECs at both the mRNA and protein levels. N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, significantly suppressed PM-induced Cx43 expression. Cx43 proteins on the plasma membrane and ER/Golgi apparatus were elevated in response to a PM challenge. In addition, PM induced gap junction activity, which was indicated by green fluorescence dye transfer between two adjacent ECs. Moreover, GAP27, a selective Cx43 channel inhibitor, attenuated PM-induced human lung EC barrier disruption, which was reflected by rescued trans-endothelial electrical resistance (TER) with an electric cell-substrate impedance sensing system. Moreover, knocking down Cx43 alleviated PM-induced myosin light chain (MLC) phosphorylation.

CONCLUSIONS: These results strongly suggest that Cx43 plays a key role in PM-mediated endothelial barrier disruption and signal transduction. Cx43 may be a therapeutic target in PM-mediated cardiopulmonary disorders.},
}

@article {pmid37685966,
year = {2023},
author = {Muñoz-Sánchez, G and Godínez-Méndez, LA and Fafutis-Morris, M and Delgado-Rizo, V},
title = {Effect of Antioxidant Supplementation on NET Formation Induced by LPS In Vitro; the Roles of Vitamins E and C, Glutathione, and N-acetyl Cysteine.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37685966},
issn = {1422-0067},
mesh = {Horses ; Animals ; *Antioxidants/pharmacology ; *Vitamin E/pharmacology ; Acetylcysteine/pharmacology ; Lipopolysaccharides/pharmacology ; Glutathione Disulfide ; Reactive Oxygen Species ; Glutathione ; Ascorbic Acid/pharmacology ; Vitamins ; Dietary Supplements ; },
abstract = {Neutrophil extracellular traps (NETs) require reactive oxygen species (ROS) to eliminate pathogens by inducing oxidative stress. However, this process can also cause tissue damage to the host. Neutrophils contain high concentrations of vitamin C (1.5 mM) compared to the bloodstream (0.1 mM), and this antioxidant can interact with vitamin E and glutathione (GSH) inside the cell to maintain the redox balance. Previous studies have investigated the effect of vitamins E or C and N-acetyl cysteine (NAC) on NET formation, but the interactions of these molecules in neutrophils remain unknown. In this study, we investigated the effect of antioxidants alone and two combinations on NET formation and oxidative stress. Neutrophils were pre-loaded with GSH + NAC or vitamin E + vitamin C + GSH + NAC (termed ALL), and LPS-induced NET formation was assessed using fluorometry and immunofluorescence. Antioxidant effects were evaluated by measuring the total antioxidant capacity (TAC), GSH/GSSG ratio, ROS production, nitrite + nitrate levels, and lipid peroxidation. Our results showed that even low doses of antioxidants are capable of decreasing NETs. Furthermore, the combinations augmented TAC and GSH/GSSG ratio and decreased ROS, nitrites + nitrates, and malondialdehyde (MDA) levels in supplemented neutrophils in vitro.},
}

Horses
Animals
*Antioxidants/pharmacology
*Vitamin E/pharmacology
Acetylcysteine/pharmacology
Lipopolysaccharides/pharmacology
Glutathione Disulfide
Reactive Oxygen Species
Glutathione
Ascorbic Acid/pharmacology
Vitamins
Dietary Supplements

@article {pmid37684590,
year = {2023},
author = {Liu, S and Guan, Y and Weng, Y and Liao, B and Tong, L and Hao, Z and Chen, J and Shi, J and Cheng, T},
title = {Genome-wide identification of the NAC gene family and its functional analysis in Liriodendron.},
journal = {BMC plant biology},
volume = {23},
number = {1},
pages = {415},
pmid = {37684590},
issn = {1471-2229},
support = {32101546//National Natural Science Foundation of China/ ; 32071784//National Natural Science Foundation of China/ ; 2021YFD2200103//National Key Research and Development Program of China during the 14th Five-year Plan Period/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; },
mesh = {*Liriodendron ; Acetylcysteine ; Cell Nucleus ; Cytoplasm ; },
abstract = {As one of the largest plant specific transcription factor families, NAC family members play an important role in plant growth, development and stress resistance. To investigate the function of NAC transcription factors during abiotic stress, as well as during somatic embryogenesis, we identified and characterized the NAC gene family in Liriodendron chinense. We found that most LcNAC members contain more than three exons, with a relatively conserved gene and motif structure, especially at the N-terminus. Interspecies collinearity analysis revealed a closer relationship between the L. chinense NACs and the P. trichocarpa NACs. We analyzed the expression of LcNAC in different tissues and under three abiotic stresses. We found that 12 genes were highly expressed during the ES3 and ES4 stages of somatic embryos, suggesting that they are involved in the development of somatic embryos. 6 LcNAC genes are highly expressed in flower organs. The expression pattern analysis of LcNACs based on transcriptome data and RT-qPCR obtained from L. chinense leaves indicated differential expression responses to drought, cold, and heat stress. Genes in the NAM subfamily expressed differently during abiotic stress, and LcNAC6/18/41/65 might be the key genes in response to abiotic stress. LcNAC6/18/41/65 were cloned and transiently transformed into Liriodendron protoplasts, where LcNAC18/65 was localized in cytoplasm and nucleus, and LcNAC6/41 was localized only in nucleus. Overall, our findings suggest a role of the NAC gene family during environmental stresses in L. chinense. This research provides a basis for further study of NAC genes in Liriodendron chinense.},
}

*Liriodendron
Acetylcysteine
Cell Nucleus
Cytoplasm

@article {pmid37683599,
year = {2023},
author = {Prescott, LF},
title = {PARACETAMOL (ACETAMINOPHEN) POISONING: THE EARLY YEARS.},
journal = {British journal of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bcp.15903},
pmid = {37683599},
issn = {1365-2125},
abstract = {Paracetamol (acetaminophen) was marketed in the 1950s as a non-prescription analgesic/antipyretic without any preclinical toxicity studies. It became used increasingly for self-poisoning, particularly in the UK and was belatedly found to cause acute liver damage which could be fatal. Management of poisoned patients was difficult as maximum abnormalities of liver function were delayed for 3 days or more after an overdose. There was no treatment and the mechanism of hepatotoxicity was not known. The paracetamol half-life was prolonged with liver damage occurring when it exceeded 4 hours and the Rumack-Matthew nomogram was an important advance that allowed stratification of patients into separate zones of risk. It is used to guide prognosis and treatment and its predictive value could be increased by combining it with the paracetamol half-life. The problems of a sheep farmer in Australia in the early 1970s led to the discovery of the mechanism of paracetamol hepatotoxicity, and the first effective treatment of overdosage with intravenous (IV) cysteamine. This had unpleasant side effects and administration was difficult. N-acetylcysteine soon became the treatment of choice for paracetamol overdose and given early it was very effective when administered either IV or orally. N-acetylcysteine could cause "anaphylactoid" reactions, particularly early during IV administration when the concentrations were highest. Simpler and shorter regimes with slower initial rates of infusion have now been introduced with a reduced incidence of these adverse effects. In addition, there has been a move to use larger doses of N-acetylcysteine given over longer periods for patients who are more severely poisoned and those with risk factors. There has been much interest recently in the search for novel biomarkers such as microRNAs, procalcitonin and cyclophilin that promise to have greater specificity and sensitivity than transaminases. Paracetamol-protein adducts predict hepatotoxicity and are specific biomarkers of toxic paracetamol metabolite exposure. Another approach would be measurement of the plasma levels of cysteine and inorganic sulphate. It is 50 years since the first effective treatment for paracetamol poisoning and apart from liver transplantation there is still no effective treatment for patients who present late.},
}

@article {pmid37681263,
year = {2023},
author = {Pepin, L and Matsler, N and Fontes, A and Heard, K and Flaherty, BF and Monte, AA},
title = {Fomepizole Therapy for Acetaminophen-Induced Liver Failure in an Infant.},
journal = {Pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1542/peds.2022-061033},
pmid = {37681263},
issn = {1098-4275},
abstract = {Acetaminophen overdose is common in the pediatric population. N-acetylcysteine (NAC) is effective at preventing liver injury in most patients when started shortly after the overdose. Delays to therapy increase risk of hepatotoxicity and liver failure that may necessitate organ transplant. Animal studies have demonstrated fomepizole may provide added benefit in acetaminophen overdose because of its ability to block the metabolic pathway that produces the toxic acetaminophen metabolite and downstream inhibition of oxidative stress pathways that lead to cell death. Several adult case reports describe use of fomepizole in patients at higher risk for poor outcomes despite NAC. We describe a case of a 7-month-old female who presented in acute liver failure with persistently elevated acetaminophen concentration secondary to repeated supratherapeutic doses of acetaminophen to manage fever. Fomepizole and NAC antidotes were used in the management of the patient. She fully recovered despite demonstrating multiple markers of poor outcome on initial presentation. Although randomized trials are lacking, this case suggests that fomepizole may safely provide additional benefit in pediatric patients at risk for severe acetaminophen toxicity.},
}

@article {pmid37680754,
year = {2023},
author = {Alqahtani, QH and Fadda, LM and Alhusaini, AM and Hasan, IH and Ali, HM},
title = {Involvement of Nrf2, JAK and COX pathways in acetaminophen-induced nephropathy: Role of some antioxidants.},
journal = {Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society},
volume = {31},
number = {10},
pages = {101752},
pmid = {37680754},
issn = {1319-0164},
abstract = {OBJECTIVES: Acetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury.

DESIGN AND METHOD: Rats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP.

RESULTS: Treatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree.

CONCLUSION: The combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.},
}

@article {pmid37670970,
year = {2023},
author = {Zhang, Z and Luan, Q and Hao, W and Cui, Y and Li, Y and Li, X},
title = {NOX4-derived ROS Regulates Aerobic Glycolysis of Breast Cancer through YAP Pathway.},
journal = {Journal of Cancer},
volume = {14},
number = {13},
pages = {2562-2573},
pmid = {37670970},
issn = {1837-9664},
abstract = {Background: NOX4 is highly expressed in breast cancer and is closely associated with cell invasion and metastasis. The involvement of NOX4 in glycolysis in breast cancer remains unclear. The aim of this study was to investigate the role and mechanism of NOX4 in glycolysis in breast cancer. Methods: NOX4 expression in breast cancer cells was detected by qRT-PCR and western blotting. siRNAs and plasmids were used to silence or enhance the expression of NOX4. The mRNA and protein expression of HK2, GLUT1, PKM2, LDHA, and YAP was detected by qRT-PCR and western blotting, and the [18]F-FDG uptake rate was detected by γ-radiometer. Detection of reactive oxygen species (ROS) in cells was performed using a commercial ROS kit. After transfection, CCK8, EDU and Transwell experiments were conducted to detect cell proliferation and migration ability. MicroPET imaging was used to detect the effects of NOX4 on tumor metabolism. Immunohistochemistry was used to detect the expression of NOX4, glycolytic enzymes HK2, GLUT1, PKM2, LDHA, the proliferation index KI67, and the activation of YAP pathway molecule. Results: In this study, the expression of NOX4 in MDA-MB-231 and MDA-MB-453 was higher than in MCF10A. qRT-PCR and western blotting experiments showed that NOX4 downregulation decreased the expression of glycolytic enzymes HK2, GLUT1, PKM2, LDHA, and 18F-FDG uptake. Conversely, the overexpression of NOX4 enhanced the expression of HK2, GLUT1, PKM2, LDHA, and 18F-FDG uptake. Proliferation and migration experiments showed that after down-regulation of NOX4, cell proliferation and migration ability decreased, while NOX4 overexpression promoted cell proliferation and migration ability. Additionally, ROS content and YAP expression decreased after NOX4 down-regulation, while ROS content and YAP expression increased following NOX4 overexpression, which was reversed by N-acetyl cysteine (NAC), a ROS inhibitor. Furthermore, exposure to NAC and Peptide17, a YAP inhibitor, blocked the increase in glycolytic enzyme expression, and the enhancement of proliferation and migration caused by NOX4 overexpression. In addition, in animal experiments, the results of the MicroPET imaging showed that the glucose metabolism rate of the NOX4 inhibitor group was significantly lower than that of the control group. ROS levels in the NOX4 inhibitor group was lower than that in the control group. Immunohistochemistry showed that the expression of HK2, GLUT1, PKM2, LDHA, KI67, and YAP in the NOX4 knock-down group were decreased. Conclusions: NOX4 affects breast cancer glycolysis through ROS-induced activation of the YAP pathway, further promoting the proliferation and migration of breast cancer cells.},
}

@article {pmid37670199,
year = {2023},
author = {Kaya, S and Yalcın, T and Tektemur, A and Kuloğlu, T},
title = {N-Acetylcysteine may exert hepatoprotective effect by regulating Meteorin-Like levels in Adriamycin-induced liver injury.},
journal = {Cell stress & chaperones},
volume = {},
number = {},
pages = {},
pmid = {37670199},
issn = {1466-1268},
support = {TF.21.11//Firat University Scientific Research Projects Management Unit/ ; },
abstract = {Adriamycin (ADR) is an important chemotherapeutic drug, but it has serious side effects such as hepatotoxicity. This study aimed to evaluate whether N-acetylcysteine (NAC) has hepatoprotective effects against ADR-induced hepatotoxicity in rats. In addition, it was aimed to determine how Meteorin-Like (MtrnL), which has pleiotropic effects on immunology, inflammation, and metabolism, is affected by ADR and/or NAC applications in liver tissue. 28 rats were randomly assigned to one of four equal groups in the study: control (no treatment), NAC (150 mg/kg/day of NAC intraperitoneally (i.p), ADR (15 mg/kg only on the first day of the experiment), and ADR + NAC (ADR 15 mg/kg on the first day of the experiment + 150 mg/kg/day NAC i.p). After 15 days, liver enzyme levels in serum, oxidant/antioxidant parameters in liver tissue, histopathological changes, caspase 3 (Casp3) and heat shock protein 70 (HSP-70) immunoreactivities, and MtrnL levels were examined. Histopathological changes, liver enzyme levels, as well as HSP-70, and Casp3 immunoreactivities increased due to ADR application. Additionally, MtrnL levels in liver tissue were significantly increased as a result of ADR application. However, it was detected that the NAC application significantly regulated the ADR-induced changes. Furthermore, it was determined that NAC administration regulated the changes in ADR-induced oxidative stress parameters. We propose that NAC may exert a hepatoprotective effect by regulating ADR-induced altered oxidative stress parameters, MtrnL levels, Casp3, and HSP-70 immunoreactivities in the liver.},
}

@article {pmid37666440,
year = {2023},
author = {Wang, X and Zhou, P and Zhang, Z and Huang, Q and Chen, X and Ji, L and Cheng, X and Shi, Y and Yu, S and Tang, J and Sun, C and Zhao, X and Yu, J},
title = {A Drosophila model of gestational antimony exposure uncovers growth and developmental disorders caused by disrupting oxidative stress homeostasis.},
journal = {Free radical biology & medicine},
volume = {208},
number = {},
pages = {418-429},
doi = {10.1016/j.freeradbiomed.2023.09.002},
pmid = {37666440},
issn = {1873-4596},
abstract = {The toxic heavy metal antimony (Sb) is ubiquitous in our daily lives. Various models have shown that Sb induces neuronal and reproductive toxicity. However, little is known about the developmental toxicity of Sb exposure during gestation and the underlying mechanisms. To study its effects on growth and development, Drosophila stages from eggs to pupae were exposed to different Sb concentrations (0, 0.3, 0.6 and 1.2 mg/mL Sb); RNA sequencing was used to identify the underlying mechanism. The model revealed that prenatal Sb exposure significantly reduced larval body size and weight, the pupation and eclosion rates, and the number of flies at all stages. With 1.2 mg/mL Sb exposure in 3rd instar larvae, 484 genes were upregulated and 694 downregulated compared to controls. Biological analysis showed that the disrupted transcripts were related to the oxidative stress pathway, as verified by reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and glutathione (GSH) intervention experiments. Sb exposure induced oxidative stress imbalance could be rectified by chelation and antioxidant effects of NAC/GSH. The Drosophila Schneider 2 (S2) model further demonstrated that NAC and GSH greatly ameliorated cell death induced by Sb exposure. In conclusion, gestational Sb exposure disrupted oxidative stress homeostasis, thereby impairing growth and development.},
}

@article {pmid37662796,
year = {2023},
author = {Çavuş, UY and Yılmaz, A and Tascanov, MB and Ocak, M},
title = {Efficacy of combination of N-acetylcysteine and primrose in spinal cord injury; an experimental study.},
journal = {Heliyon},
volume = {9},
number = {9},
pages = {e19350},
pmid = {37662796},
issn = {2405-8440},
abstract = {INTRODUCTION: Spinal cord trauma represents a major cause of emergency department admissions, with high morbidity and mortality rates. It requires early and urgent treatment. This experimental study assessed the effectiveness of a combination of primrose and N-acetylcysteine (NAC) in managing spinal cord injury (SCI).

METHODS: We divided 46 adult male Wistar albino rats (6-8 months old, weighing 300-350 g) into five groups. Group 1 (n = 10) received only primrose; group 2 (n = 10) received only NAC; group 3 (n = 10) received a combination of NAC and primrose; group 4 (n = 10) received no intervention (first control group); group 5 (n = 10) underwent laminectomy only (second control group). Intergroup neurological and motor function were evaluated on days 1, 7, and 14. Oxidative biochemical markers, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA), were measured.

RESULTS: Significant differences were recorded in the GPX, SOD, and MDA values of groups 1, 2, 3, and 4 (p < 0.001, p = 0.005, and p = 0.097, respectively). Groupwise comparisons were conducted to identify the clinical significance of these markers. GPX and SOD levels were significantly higher in group 1 than in group 2; MDA levels were lower in group 1. GPX and SOD levels were significantly higher than in group 3 than in group 1; MDA levels were lower in group 3. Compared with group 5, group 1 demonstrated significantly higher GPX and SOD levels and lower MDA levels. Results in group 2 were similar to results in group 5. In group 3, GPX and SOD levels were significantly higher than in groups 2 and 5; MDA levels were significantly lower. Comparisons according to inclined plane angle level and motor function values revealed significant results on day 14, in favor of group 3 rats that had received the combined treatment.

CONCLUSION: The combined administration of NAC and primrose for traumatic SCI was more effective than either treatment alone in terms of improving biochemical and neurological functions. These findings suggest that the combination of NAC and primrose can serve as an effective treatment option for traumatic SCI.},
}

@article {pmid37661403,
year = {2023},
author = {Kadota, Y and Yamanokuchi, R and Ohnishi, N and Matsuoka, M and Kawakami, T and Sato, M and Suzuki, S},
title = {Metallothionein Gene Deficiency Facilitates the Differentiation of C2C12 Myoblasts into Slow-Twitch Myotubes.},
journal = {Biological & pharmaceutical bulletin},
volume = {46},
number = {9},
pages = {1240-1248},
doi = {10.1248/bpb.b23-00165},
pmid = {37661403},
issn = {1347-5215},
mesh = {Animals ; Mice ; *Muscle Fibers, Skeletal ; Cell Differentiation ; *Muscle, Skeletal ; Myoblasts ; Muscular Atrophy ; Acetylcysteine ; Antioxidants ; },
abstract = {Metallothionein (MT) 1 and 2 are ubiquitously expressed cysteine-rich, low molecular weight proteins. MT expression is upregulated in skeletal muscle during aging. MTs also play role in multiple types of skeletal muscle atrophy. Meanwhile, it has been reported that MT1 and MT2 gene deficiency increases myogenesis in MT knockout (MTKO) mice. However, little is known about the effect of MTs on muscle formation and atrophy. In this study, we investigated the effect of MT1 and MT2 gene knock-out using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CRISPR-Cas9) system in an in vitro skeletal muscle differentiation model (C2C12 cell line). MT deficiency promoted myogenic differentiation and myotube formation in C2C12 cells. Muscle-specific transcription factors MyoD and myogenin were found to be upregulated at the late stage of myotube differentiation in MTKO cells. Furthermore, the fast-twitch myosin heavy chain (MyHC) protein expression was similar in MTKO and mock-transfected myotubes, but slow-MyHC expression was higher in MTKO cells than in mock cells. The MT gene deletion did not affect the number of fast MyHC-positive myotubes but increased the number of slow MyHC-positive myotubes. Treatment with the antioxidant N-acetylcysteine (NAC) inhibited the increase in the number of slow MyHC-positive myotubes as well as slow-MyHC expression in MTKO cells. In contrast, NAC treatment did not alter the number of fast MyHC-positive myotubes or the expression of fast-MyHC in MTKO cells. These results suggest that the antioxidant effects of MTs may be involved in slow-twitch myofiber formation in skeletal muscle.},
}

Animals
Mice
*Muscle Fibers, Skeletal
Cell Differentiation
*Muscle, Skeletal
Myoblasts
Muscular Atrophy
Acetylcysteine
Antioxidants

@article {pmid37659111,
year = {2023},
author = {Fraternale, A and Green, KA and Schiavano, GF and Bruschi, M and Retini, M and Magnani, M and Green, WR},
title = {Inhibition of myeloid-derived suppressor cell (MDSC) activity by redox-modulating agents restores T and B cell proliferative responses in murine AIDS.},
journal = {International immunopharmacology},
volume = {124},
number = {Pt A},
pages = {110882},
doi = {10.1016/j.intimp.2023.110882},
pmid = {37659111},
issn = {1878-1705},
abstract = {The mechanisms by which myeloid-derived suppressor cells (MDSCs) mediate inhibition prominently include the production of reactive nitrogen species, in particular those generated by inducible nitric oxide synthase (iNOS), and reactive oxygen species. LP-BM5 murine retroviral infection results in a profound immunodeficiency, known as murine AIDS, as well as in increased numbers and activity of monocytic-type MDSCs (M-MDSCs) that suppress both T and B cell responses. While M-MDSCs suppress T cells ex vivo in a fully iNOS/NO-dependent manner, M-MDSC suppression of B cell responses is only partially due to iNOS/NO. This study preliminarily explored the role of two redox-modulating compounds in inhibiting the M-MDSC suppressive activity in LP-BM5 infection. The tested molecules were: I-152 consisting in a conjugate of N-acetyl-cysteine (NAC) and S-acetyl-cysteamine (SMEA) and C4-GSH that is the n-butanoyl glutathione (GSH) derivative. The results show that both molecules, tested in a concentration range between 3 and 20 mM, blocked the M-MDSC suppression of activated B and T cells ex vivo and restored their proliferative capacity in vivo. Ex vivo I-152 blockade of M-MDSC suppressiveness was more significant for T cell (about 70%) while M-MDSC blockade by C4-GSH was preferential for B cell responsiveness (about 60%), which was also confirmed by in vivo investigation. Beyond insights into redox-dependent suppressive effector mechanism(s) of M-MDSCs in LP-BM5 infection, these findings may ultimately be important to identify new immunotherapeutics against infectious diseases.},
}

@article {pmid37654348,
year = {2023},
author = {Veeraiyan, M and Kumar, YP and Chandhar, CY and Priyanka, Y and Jaiswal, M and Kemasaram, D},
title = {Evaluation of Smear Layer Removal and Micro Hardness Alteration of Radicular Dentin after Using Various Chelating Agents - An Atomic Force Microscopic Study.},
journal = {Journal of pharmacy & bioallied sciences},
volume = {15},
number = {Suppl 1},
pages = {S582-S587},
pmid = {37654348},
issn = {0976-4879},
abstract = {BACKGROUND AND AIMS: For endodontic therapy to be successful, the smear layer produced by the root canal instruments must be removed. The study's objective is to evaluate the effectiveness of radicular dentin microhardness modification and smear layer removal utilizing various chelating agents.

MATERIALS AND METHODS: Extracted human mandibular single-rooted premolar teeth were selected for the study. The specimens were sectioned to obtain a standard root length and, working length determination was done. Cleaning and shaping were done in all the samples till the size F3 (Protaper universal). Based on the chelating agents using samples were randomly divided into four groups, Group-I: Saline (negative control), Group-II: 17% EDTA (DeSmear, Ahmedabad, Gujarat) (positive control), Group-III: 0.2% Chitosan (Everest-Biotech, Bengaluru), Group-IV: 20% N-Acetyl cysteine (NAC) (Sisco Research Laboratories, Mumbai), Group-V: 5% Pentetic acid (New Alliance Fine chem Pvt Ltd, Mumbai). All the samples were prepared for smear layer removal and surface roughness evaluation using an atomic force microscope.

RESULTS: It was observed that significantly (P = 0.000) the mean roughness average was higher among group II EDTA (148 ± 8.5) followed by group III 0.2% Chitosan (92.5 ± 3.42), group IV 20% NAC (85.2 ± 2.17), and group V 5% Pentetic acid (73.3 ± 3.39) and least by group I Saline (59.3 ± 3.31). The highest smear layer removal was seen with group II (EDTA) followed by group III (0.2% Chitosan), group IV (20% NAC), and group V (Pentetic acid).

CONCLUSION: All the chelating agents removed smear layer in coronal third, middle third whereas none of them were able to entirely eliminate from the apical third. Chitosan with smear layer removal capacity equal to EDTA with limited roughness can be considered as a valid alternative as final irrigant.},
}

@article {pmid37654090,
year = {2023},
author = {Frediani, JK and Lal, AA and Kim, E and Leslie, SL and Boorman, DW and Singh, V},
title = {The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.},
journal = {Pain practice : the official journal of World Institute of Pain},
volume = {},
number = {},
pages = {},
doi = {10.1111/papr.13291},
pmid = {37654090},
issn = {1533-2500},
abstract = {BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases.

OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults.

EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence.

FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.

CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.},
}

@article {pmid37652392,
year = {2023},
author = {Xu, Y and Zhao, Z and Geng, Z and Zhou, H and Yang, C and Wang, Y and Kuerban, B and Xiao, Y and Luo, G},
title = {Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.},
journal = {Protein expression and purification},
volume = {212},
number = {},
pages = {106360},
doi = {10.1016/j.pep.2023.106360},
pmid = {37652392},
issn = {1096-0279},
abstract = {Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.},
}

@article {pmid37647428,
year = {2023},
author = {Sun, X and Sun, Y and Cao, S and Liu, X},
title = {Effects of N-acetyl-L-cysteine polysulfides on periodontitis in a mouse model.},
journal = {Immunity, inflammation and disease},
volume = {11},
number = {8},
pages = {e959},
pmid = {37647428},
issn = {2050-4527},
mesh = {Animals ; Mice ; *Acetylcysteine/pharmacology ; Lipopolysaccharides/toxicity ; Toll-Like Receptor 4/genetics ; *Periodontitis/drug therapy ; Tumor Necrosis Factor-alpha ; Disease Models, Animal ; },
abstract = {BACKGROUND: Polysulfides are reported to be involved in various important biological processes. N-acetyl-l-cysteine polysulfide with 2 sulfane sulfur atoms (NAC-S2) regulates diverse toll-like receptor (TLR) signaling pathways. Here, we aimed to determine the role of NAC-S2 in periodontitis and explore the potential mechanism.

METHODS: A periodontitis mouse model was established by ligating the subgingival between the first and second molars in wild-type, TLR4[-/-] , and Myd88[-/-] mice.

RESULTS: NAC-S2 did not affect the proportion of macrophages (CD11b[+] F4/80[+]) or neutrophils (CD11b[+] GR-1[+]) in the bone marrow. Mechanically, lipopolysaccharides (LPS), Zymosan A, or poly I: C induced tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1β expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of IκB-α, p65, and IκB kinase (IKK)-β induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor β-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cemento-enamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1β, while such phenomena could not be observed in TLR4 deficiency or Myd88 deficiency mice.

CONCLUSIONS: All of these results indicate that NAC-S2 ameliorates TLR4/NF-κB pathway mediated inflammation in mouse periodontitis model.},
}

Animals
Mice
*Acetylcysteine/pharmacology
Lipopolysaccharides/toxicity
Toll-Like Receptor 4/genetics
*Periodontitis/drug therapy
Tumor Necrosis Factor-alpha
Disease Models, Animal

@article {pmid37645523,
year = {2023},
author = {Mi, K and Wu, S and Lv, C and Meng, Y and Yin, W and Li, H and Li, J and Yuan, H},
title = {Comparing the efficacy and safety of medications in adults with hypertrophic cardiomyopathy: a systematic review and network meta-analysis.},
journal = {Frontiers in cardiovascular medicine},
volume = {10},
number = {},
pages = {1190181},
pmid = {37645523},
issn = {2297-055X},
abstract = {BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. The purpose of this study was to evaluate the efficacy and safety of several medications and recommend better drug treatments for adults with HCM.

METHODS: A review of PubMed, Embase, the Cochrane Controlled Register of Trials (CENTRAL), ClinicalTrials.gov and CNKI databases was conducted for studies on the efficacy and safety of drugs for adults with HCM. A frequentist random effects model was used in this network analysis.

RESULTS: This network meta-analysis included 7 studies assessing seven medications, 6 studies evaluating monotherapy and 1 study evaluating combination therapy. Based on the network meta-analysis results, xiaoxinbi formula plus metoprolol (MD -56.50% [-72.43%, -40.57%]), metoprolol (MD -47.00% [-59.07%, -34.93%]) and mavacamten (MD -34.50% [-44.75%, -24.25%]) significantly reduced the resting left ventricular outflow tract gradient (LVOTG) in comparison with placebo. Resting LVOTG could also be reduced with N-acetylcysteine (NAC). The incidence of adverse drug reactions was not significantly different between the placebo group and the treatment group.

CONCLUSION: For adults with HCM, the top 4 treatments included xiaoxinbi formula plus metoprolol, metoprolol, mavacamten and NAC.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=374222], identifier [CRD42022374222].},
}

@article {pmid37635852,
year = {2023},
author = {Ng, WW and Tong, HF and Ng, WY and Yeung, JK and Young, JK and Woo, RK and Wong, MM},
title = {Pyroglutamic Acidosis - An Underrecognised Entity Associated with Acetaminophen Use.},
journal = {Romanian journal of anaesthesia and intensive care},
volume = {30},
number = {1},
pages = {26-30},
pmid = {37635852},
issn = {2392-7518},
abstract = {Pyroglutamic acidosis (PGA) is an underrecognized entity characterised by raised anion gap metabolic acidosis (RAGMA) and urinary hyper-excretion of pyroglutamic acid. It is frequently associated with chronic acetaminophen (APAP) ingestion. We report the case of a 73-year-old man with invasive pulmonary aspergillosis treated with voriconazole and APAP for analgesia with a cumulative dose of 160 g over 40 days. PGA was suspected as he developed severe RAGMA and common causes were excluded. Diagnosis was confirmed via urinary organic acid analysis which showed significant hyper-excretion of pyroglutamic acid. APAP was discontinued, and N-acetylcysteine (NAC) was administered. His RAGMA rapidly resolved following treatment.},
}

@article {pmid37634582,
year = {2023},
author = {Feng, C and Bai, H and Chang, X and Wu, Z and Dong, W and Ma, Q and Yang, J},
title = {Aflatoxin B1-induced early developmental hepatotoxicity in larvae zebrafish.},
journal = {Chemosphere},
volume = {340},
number = {},
pages = {139940},
doi = {10.1016/j.chemosphere.2023.139940},
pmid = {37634582},
issn = {1879-1298},
mesh = {Animals ; Aflatoxin B1/toxicity ; Zebrafish/genetics ; *Fatty Liver ; Acetylcysteine ; Larva/genetics ; *Chemical and Drug Induced Liver Injury ; },
abstract = {Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.},
}

Animals
Aflatoxin B1/toxicity
Zebrafish/genetics
*Fatty Liver
Acetylcysteine
Larva/genetics
*Chemical and Drug Induced Liver Injury

@article {pmid37632646,
year = {2023},
author = {Chen, HY and Chen, RLC and Hsieh, BC and Cheng, TJ},
title = {Determination of o-phthalaldehyde for dose verification of the clinical disinfectant by fluorescent sequential injection analysis.},
journal = {Analytical sciences : the international journal of the Japan Society for Analytical Chemistry},
volume = {},
number = {},
pages = {},
pmid = {37632646},
issn = {1348-2246},
support = {MOST-105-2313-B-002-022//Ministry of Science and Technology of Taiwan/ ; MOST-107-2313-B-002-015//Ministry of Science and Technology of Taiwan/ ; },
abstract = {A new automated, generic analytical approach for determining the clinical disinfectant o-phthalaldehyde (OPA) is reported in this study. The proposed sequential injection analysis (SIA) is based on the online reaction of the OPA with glycine/N-acetylcysteine (NAC) in a neutral medium (pH = 7.0) to form a highly fluorescent isoindole derivative. All critical flow and reaction variables were investigated, while validation was carried out in the linearity detection range (0.0075-0.02%). As a result, excellent linearity (R[2] > 0.99) and precision (1.5-2.4% for repeatability and 0.7-2.2% for reproducibility) were achieved for the reference OPA solutions. Furthermore, reasonable concentration verification of OPA disinfection (0.2-0.6%) in healthcare institutes can be achieved using the developed fluorescent SIA due to its good sensitivity (0.111 V/%) and precision (1.0-2.3% for intermediate precision) around the minimum effective concentration (MEC) of 0.3% for Cidex-OPA disinfectant.},
}

@article {pmid37631065,
year = {2023},
author = {Blagov, AV and Orekhova, VA and Sukhorukov, VN and Melnichenko, AA and Orekhov, AN},
title = {Potential Use of Antioxidant Compounds for the Treatment of Inflammatory Bowel Disease.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {8},
pages = {},
pmid = {37631065},
issn = {1424-8247},
support = {23-65-10014//Russian Science Foundation/ ; },
abstract = {Since inflammatory bowel diseases (IBDs) are chronic, the development of new effective therapeutics to combat them does not lose relevance. Oxidative stress is one of the main pathological processes that determines the progression of IBD. In this regard, antioxidant therapy seems to be a promising approach. The role of oxidative stress in the development and progression of IBD is considered in detail in this review. The main cause of oxidative stress in IBD is an inadequate response of leukocytes to dysbiosis and food components in the intestine. Passage of immune cells through the intestinal barrier leads to increased ROS concentration and the pathological consequences of exposure to oxidative stress based on the development of inflammation and impaired intestinal permeability. To combat oxidative stress in IBD, several promising natural (curcumin, resveratrol, quercetin, and melatonin) and artificial antioxidants (N-acetylcysteine (NAC) and artificial superoxide dismutase (aSOD)) that had been shown to be effective in a number of clinical trials have been proposed. Their mechanisms of action on pathological events in IBD and clinical manifestations from their impact have been determined. The prospects for the use of other antioxidants that have not yet been tested in the treatment of IBD, but have the properties of potential therapeutic candidates, have been also considered.},
}

@article {pmid37628913,
year = {2023},
author = {Alkandari, AF and Madhyastha, S and Rao, MS},
title = {N-Acetylcysteine Amide against Aβ-Induced Alzheimer's-like Pathology in Rats.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37628913},
issn = {1422-0067},
support = {YM07/19//Kuwait University/ ; },
mesh = {Male ; Rats ; Animals ; Acetylcysteine/pharmacology ; Rats, Wistar ; *Alzheimer Disease/chemically induced/drug therapy ; Synaptophysin ; *Neuroprotective Agents/pharmacology ; Amyloid beta-Peptides ; Gliosis/chemically induced/drug therapy ; Glutathione ; },
abstract = {Oxidative stress with a depletion of glutathione is a key factor in the initiation and progression of Alzheimer's disease (AD). N-Acetylcysteine (NAC), a glutathione precursor, provides neuroprotective effects in AD animal models. Its amide form, N-Acetylcysteine amide (NACA), has an extended bioavailability compared to NAC. This study evaluates the neuroprotective effects of NACA against Aβ1-42 peptide-induced AD-like pathology in rats. Male Wistar rats (2.5 months old) were divided into five groups: Normal Control (NC), Sham (SH), Aβ, Aβ + NACA and NACA + Aβ + NACA (n = 8 in all groups). AD-like pathology was induced by the intracerebroventricular infusion of Aβ1-42 peptide into the lateral ventricle. NACA (75 mg/kg) was administered either as a restorative (i.e., injection of NACA for 7 consecutive days after inducing AD-like pathology (Aβ + N group)), or as prophylactic (for 7 days before and 7 days after inducing the pathology (N + Aβ + N group)). Learning and memory, neurogenesis, expression of AD pathology markers, antioxidant parameters, neuroprotection, astrogliosis and microgliosis were studied in the hippocampus and the prefrontal cortex. All data were analyzed with a one-way ANOVA test followed by Bonferroni's multiple comparison test. NACA treatment reversed the cognitive deficits and reduced oxidative stress in the hippocampus and prefrontal cortex. Western blot analysis for Tau, Synaptophysin and Aβ, as well as a histopathological evaluation through immunostaining for neurogenesis, the expression of neurofibrillary tangles, β-amyloid peptide, synaptophysin, neuronal morphology and gliosis, showed a neuroprotective effect of NACA. In conclusion, this study demonstrates the neuroprotective effects of NACA against β-amyloid induced AD-like pathology.},
}

Male
Rats
Animals
Acetylcysteine/pharmacology
Rats, Wistar
*Alzheimer Disease/chemically induced/drug therapy
Synaptophysin
*Neuroprotective Agents/pharmacology
Amyloid beta-Peptides
Gliosis/chemically induced/drug therapy
Glutathione

@article {pmid37628819,
year = {2023},
author = {Heiserman, JP and Minhas, Z and Nikpayam, E and Cheon, DJ},
title = {Targeting Heat Shock Protein 27 and Fatty Acid Oxidation Augments Cisplatin Treatment in Cisplatin-Resistant Ovarian Cancer Cell Lines.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37628819},
issn = {1422-0067},
support = {1/CX/CSRD VA/United States ; },
mesh = {Humans ; Female ; *Cisplatin/pharmacology ; HSP27 Heat-Shock Proteins/genetics ; Reactive Oxygen Species ; Neoplasm Recurrence, Local ; *Ovarian Neoplasms/drug therapy ; Cell Line ; Fatty Acids ; },
abstract = {Most ovarian cancer patients develop recurrent cancers which are often resistant to commonly employed chemotherapy agents, such as cisplatin. We have previously shown that the inhibition of heat shock protein 27 (HSP27) or fatty acid oxidation (FAO) sensitizes cisplatin-resistant ovarian cancer cell lines to cisplatin and dual inhibition of both HSP27 and FAO induces substantial cell death in vitro. However, it is unclear how HSP27 and FAO promote cisplatin resistance, and if dual inhibition of both HSP27 and FAO would augment cisplatin treatment in vivo. Here we showed that HSP27 knockdown in two cisplatin-resistant ovarian cancer cell lines (A2780CIS and PEO4) resulted in more ROS production upon cisplatin treatment. HSP27-knockdown cancer cells exhibited decreased levels of reduced glutathione (GSH) and glucose6phosphate dehydrogenase (G6PD), a crucial pentose phosphate pathway enzyme. ROS depletion with the compound N-acetyl cysteine (NAC) attenuated cisplatin-induced upregulation of HSP27, FAO, and markers of apoptosis and ferroptosis in cisplatin-resistant ovarian cancer cell lines. Finally, inhibition of HSP27 and FAO with ivermectin and perhexiline enhanced the cytotoxic effect of cisplatin in A2780CIS xenograft tumors in vivo. Our results suggest that two different cisplatin-resistant ovarian cancer cell lines upregulate HSP27 and FAO to deplete cisplatin-induced ROS to attenuate cisplatin's cytotoxic effect.},
}

Humans
Female
*Cisplatin/pharmacology
HSP27 Heat-Shock Proteins/genetics
Reactive Oxygen Species
Neoplasm Recurrence, Local
*Ovarian Neoplasms/drug therapy
Cell Line
Fatty Acids

@article {pmid37628771,
year = {2023},
author = {Staskiewicz, A and Wong, E and Tucker, M and Farhin, R and Park, J and Saade, R and Alkhazali, T and Dang, T and Wang, X},
title = {Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37628771},
issn = {1422-0067},
mesh = {Humans ; Bortezomib/pharmacology ; Caspase 3 ; *Multiple Myeloma/drug therapy ; Antioxidants ; *Antineoplastic Agents ; Resveratrol/pharmacology ; Tumor Microenvironment ; },
abstract = {Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 μM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells.},
}

Humans
Bortezomib/pharmacology
Caspase 3
*Multiple Myeloma/drug therapy
Antioxidants
*Antineoplastic Agents
Resveratrol/pharmacology
Tumor Microenvironment

@article {pmid37627587,
year = {2023},
author = {Cuevas-López, B and Romero-Ramirez, EI and García-Arroyo, FE and Tapia, E and León-Contreras, JC and Silva-Palacios, A and Roldán, FJ and Campos, ONM and Hernandez-Esquivel, L and Marín-Hernández, A and Gonzaga-Sánchez, JG and Hernández-Pando, R and Pedraza-Chaverri, J and Sánchez-Lozada, LG and Aparicio-Trejo, OE},
title = {NAC Pre-Administration Prevents Cardiac Mitochondrial Bioenergetics, Dynamics, Biogenesis, and Redox Alteration in Folic Acid-AKI-Induced Cardio-Renal Syndrome Type 3.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {8},
pages = {},
pmid = {37627587},
issn = {2076-3921},
support = {21-1252//Instituto Nacional de Cardiología/ ; },
abstract = {The incidence of kidney disease is increasing worldwide. Acute kidney injury (AKI) can strongly favor cardio-renal syndrome (CRS) type 3 development. However, the mechanism involved in CRS development is not entirely understood. In this sense, mitochondrial impairment in both organs has become a central axis in CRS physiopathology. This study aimed to elucidate the molecular mechanisms associated with cardiac mitochondrial impairment and its role in CRS development in the folic acid-induced AKI (FA-AKI) model. Our results showed that 48 h after FA-AKI, the administration of N-acetyl-cysteine (NAC), a mitochondrial glutathione regulator, prevented the early increase in inflammatory and cell death markers and oxidative stress in the heart. This was associated with the ability of NAC to protect heart mitochondrial bioenergetics, principally oxidative phosphorylation (OXPHOS) and membrane potential, through complex I activity and the preservation of glutathione balance, thus preventing mitochondrial dynamics shifting to fission and the decreases in mitochondrial biogenesis and mass. Our data show, for the first time, that mitochondrial bioenergetics impairment plays a critical role in the mechanism that leads to heart damage. Furthermore, NAC heart mitochondrial preservation during an AKI event can be a valuable strategy to prevent CRS type 3 development.},
}

@article {pmid37625774,
year = {2023},
author = {Jhuo, JY and Tong, ZJ and Ku, PH and Cheng, HW and Wang, HT},
title = {Acrolein induces mitochondrial dysfunction and insulin resistance in muscle and adipose tissues in vitro and in vivo.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {336},
number = {},
pages = {122380},
doi = {10.1016/j.envpol.2023.122380},
pmid = {37625774},
issn = {1873-6424},
abstract = {Type 2 diabetes mellitus (DM) is a common chronic condition characterized by persistent hyperglycemia and is associated with insulin resistance (IR) in critical glucose-consuming tissues, including skeletal muscle and adipose tissue. Oxidative stress and mitochondrial dysfunction are known to play key roles in IR. Acrolein is a reactive aldehyde found in the diet and environment that is generated as a fatty acid product through the glucose autooxidation process under hyperglycemic conditions. Our previous studies have shown that acrolein impairs insulin sensitivity in normal and diabetic mice, and this effect can be reversed by scavenging acrolein. This study demonstrated that acrolein increased oxidative stress and inhibited mitochondrial respiration in differentiated C2C12 myotubes and differentiated 3T3-L1 adipocytes. As a result, insulin signaling pathways were inhibited, leading to reduced glucose uptake. Treatment with acrolein scavengers, N-acetylcysteine, or carnosine ameliorated mitochondrial dysfunction and inhibited insulin signaling. Additionally, an increase in acrolein expression correlated with mitochondrial dysfunction in the muscle and adipose tissues of diabetic mice. These findings suggest that acrolein-induced mitochondrial dysfunction contributes to IR, and scavenging acrolein is a potential therapeutic approach for treating IR.},
}

@article {pmid37625683,
year = {2023},
author = {Zhao, S and Li, Y and Li, G and Ye, J and Wang, R and Zhang, X and Li, F and Gao, C and Li, J and Jiang, J and Mi, Y},
title = {PI3K/mTOR inhibitor VS-5584 combined with PLK1 inhibitor exhibits synergistic anti-cancer effects on non-small cell lung cancer.},
journal = {European journal of pharmacology},
volume = {957},
number = {},
pages = {176004},
doi = {10.1016/j.ejphar.2023.176004},
pmid = {37625683},
issn = {1879-0712},
abstract = {Small molecule drugs are of significant importance in the treatment of non-small cell lung cancer (NSCLC). Here, we explored biological effects of the PI3K/mTOR inhibitor VS-5584 on NSCLC. Our findings indicated that VS-5584 administration resulted in a dose-dependent inhibition of NSCLC cell proliferation, as well as the induction of apoptosis and cycle arrest. Additionally, we observed a significant increase in intracellular reactive oxygen species (ROS) levels following VS-5584 treatment. The use of the ROS inhibitor N-acetylcysteine (NAC) effectively reduced ROS levels and decreased the proportion of apoptotic cells. Treatment with VS-5584 led to an upregulation of genes associated with apoptosis and cell cycle, such as c-caspase 3 and P21. Conversely, a downregulation of cyclin-dependent kinase 1 (CDK1) expression was observed. Next, transcriptome analyses revealed that VS-5584 treatment altered the abundance of 1520 genes/transcripts in PC-9 cells, one of which was polo-like kinase 1 (PLK1). These differentially expressed genes were primarily enriched in biological processes such as cell cycle regulation and cell apoptosis, which are closely linked to the P53 and apoptosis pathways. Co-treatment with VS-5584 and PLK1 inhibitor NMS-P937 resulted in enhanced cancer cell death, exhibiting synergistic inhibitory activity. Notably, VS-5584 inhibited the growth of NSCLC in a patient-derived xenograft (PDX) mouse model without observable abnormalities in major organs. Overall, VS-5584 effectively suppressed the growth of NSCLC cells both in vitro and in vivo. VS-5584 combined with NMS-P937 exhibited a synergistic effect in inhibiting NSCLC cell growth. These findings suggest that VS-5584 has potential as a therapeutic strategy for treating NSCLC.},
}

@article {pmid37621062,
year = {2023},
author = {Chen, H and Zhou, H and Luo, C and Zong, K and Fu, Y and Li, W and Luo, C and Xue, G and Jiang, E and Duan, Y and Luo, T and Jiang, Y},
title = {Efficacy of treatment with N-acetylcysteine inhalation for AECOPD: A propensity-score-matched cohort study.},
journal = {The clinical respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/crj.13690},
pmid = {37621062},
issn = {1752-699X},
support = {2021-55//Social Undertakings and Livelihood Security Special Projects, the Science and Technology Bureau of Banan District, Chongqing/ ; },
abstract = {INTRODUCTION: N-acetylcysteine (NAC) prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the value of NAC inhalation in the treatment of patients with AECOPD is still poorly understood. The study was conducted to evaluate the efficacy of NAC inhalation in AECOPD patients requiring hospitalization.

METHODS: In this single institutional, retrospective cohort study, all patients with AECOPD requiring hospitalization between January 2021 and January 2022 were included. Patients were divided into NAC group and Non-NAC group according to whether being treated with NAC inhalation and were matched using the propensity score. The primary outcome was a composite of progression to ventilation requirement, in-hospital mortality and readmission for AECOPD within 30 days. The effect on the mean hospitalized days, blood gas indexes and the incidence rate of adverse drug events were compared between the two groups.

RESULTS: Ninety-six patients in the NAC group were matched with 96 patients in the Non-NAC group. The differences in the primary composite end point (NAC group vs Non-NAC group, 5.2% vs 16.7%; P = 0.011) were significant. The median time to discharge was shorter in the NAC group (8.3 vs. 9.1 days, P = 0.030). The NAC group presented a larger increase in partial pressure of arterial oxygen (Pa O2) and a higher ratio of self-reported symptomatic improvement from admission to day 5. There was no definite difference between the two groups in the frequency of adverse event.

CONCLUSION: NAC inhalation is associated with an improved clinical outcome. A further study should be conducted to confirm the clinical usefulness of NAC inhalation in AECOPD patients.},
}

@article {pmid37611476,
year = {2023},
author = {Sun, S and Zhang, C and Zhang, Q and Li, C and Huang, D and Ding, R and Cao, J and Hao, J},
title = {Role of ROS-mediated PERK/ATF4 signaling activation in extracorporeal tube formation injury of human umbilical vein endothelial cells induced by cooking oil fume PM2.5 exposure.},
journal = {Ecotoxicology and environmental safety},
volume = {263},
number = {},
pages = {115332},
doi = {10.1016/j.ecoenv.2023.115332},
pmid = {37611476},
issn = {1090-2414},
abstract = {Cooking oil fume-derived PM2.5 (COF-PM2.5) is a major source of indoor air contamination in China, which has been demonstrated to be a hazard factor of cardiovascular and cerebrovascular diseases. This study aimed to investigate the role of ROS-mediated PERK/ATF4 signaling activation in COF-PM2.5-inhibited extracorporeal tube formation in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 100 μg/mL COF-PM2.5 at different times, with or without 100 nM PERK activity inhibitor GSK2606414 (GSK) or 200 μM antioxidant N-acetylcysteine (NAC) pretreatment. Our results showed that COF-PM2.5 exposure can inhibit extracorporeal tube formation and down-regulate VEGFR2 expression in HUVECs. Furthermore, our data indicated that COF-PM2.5 exposure can activate the PERK/ATF4 signaling in HUVECs. Mechanistically, pretreatment with GSK interdicted PERK/ATF4 signaling, thereby reversing COF-PM2.5-downregulated VEGFR2 protein expression in HUVECs. Furthermore, NAC reversed VEGFR2 expression downregulated induced by COF-PM2.5 by inhibiting the upregulation of intracellular ROS levels and PERK/ATF4 signaling in HUVECs. As above, COF-PM2.5 exposure could induce ROS release from HUVECs, which in turn activate the endoplasmic reticulum PERK/ATF4 signaling and inhibit tube formation of HUVECs.},
}

@article {pmid37609158,
year = {2023},
author = {Gupta, K and Chen, D and Wells, RG},
title = {Microcystin-RR is a biliary toxin selective for neonatal cholangiocytes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37609158},
abstract = {BACKGROUND AND AIMS: Biliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to be caused by a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in toxin-induced biliary atresia in Australian livestock, but is found in a limited location and is highly unlikely to be a significant human toxin. We hypothesized that other molecules with α-methylene ketone groups, some with the potential for significant human exposure, might also be biliary toxins.

APPROACH AND RESULTS: We focused on the family of microcystins, cyclic peptide toxins from blue-green algae that have an α-methylene ketone group and are found worldwide, particularly during harmful algal blooms. We found that microcystin-RR, but not 6 other microcystins, caused damage to cell spheroids made using cholangiocytes isolated from 2-3-day-old mice, but not from adult mice. We also found that microcystin- RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice, but not 18-day-old mice. Microcystin-RR caused elevated reactive oxygen species in neonatal cholangiocytes, and treatment with N-acetyl cysteine partially prevented microcystin-RR- induced lumen closure, suggesting a role for redox homeostasis in its mechanism of action.

CONCLUSIONS: This study highlights the potential for environmental toxins to cause neonatal biliary disease and identifies microcystin-RR acting via increased redox stress as a possible neonatal bile duct toxin.},
}

@article {pmid37607187,
year = {2023},
author = {da Silva, RHS and de Moura, M and de Paula, L and Arantes, KC and da Silva, M and de Amorim, J and Miguel, MP and Martins, DB and de Melo E Silva, D and Melo, MM and Botelho, AFM},
title = {Effects of coenzyme Q10 and N-acetylcysteine on experimental poisoning by paracetamol in Wistar rats.},
journal = {PloS one},
volume = {18},
number = {8},
pages = {e0290268},
pmid = {37607187},
issn = {1932-6203},
mesh = {Adult ; Humans ; Rats ; Animals ; *Acetylcysteine/pharmacology/therapeutic use ; *Acetaminophen ; Rats, Wistar ; Saline Solution ; },
abstract = {Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common clinical signs result from damage to red blood cells and hepatocytes, and this intoxication is considered a model for the induction of acute liver failure. In the present study, the hepatoprotective effects of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC) against experimental paracetamol (PAR) poisoning were analysed. Thirty-five adult Wistar rats (Rattus novergicus albinus) were randomly assigned to five groups, and thirty-one of these survived the treatments. Negative control group (CON-) received 1mL of 0.9% NaCl orally (PO). Other groups received 1.2g/kg of PAR (PO). Positive control group (CON+) received only PAR. NAC group received 800 mg/kg intraperitoneally (IP) of NAC 1h after the administration of PAR and at 12 h received 1mL of 0.9% NaCl, IP. The fourth group (CoQ10) received 1h and 12 h after intoxication, CoQ10 (10mg/kg IP). And the fifth group (NAC+CoQ10) received NAC (800mg/kg, IP) and CoQ10 (10mg/kg, IP). After 12 hours, the rats were euthanized and necropsied to collect liver and kidney tissues for histopathological evaluation and electronic microscopy. A single dose of PAR caused severe acute hepatitis. NAC couldn't reverse the liver and kidney damages. The group that received CoQ10 and NAC had moderate liver damage, while the group that received only CoQ10 had lower values of liver enzymes and mild liver and kidney damage. Animals that received treatment with CoQ10 or NAC+CoQ10 presented normal hepatocyte mitochondria and nuclei. Although CoQ10 couldn't reverse PAR organ damage, results indicate promising hepatoprotection in Wistar rats.},
}

Adult
Humans
Rats
Animals
*Acetylcysteine/pharmacology/therapeutic use
*Acetaminophen
Rats, Wistar
Saline Solution

@article {pmid37604367,
year = {2023},
author = {Wang, X and Tian, X and Yan, H and Zhu, T and Ren, H and Zhou, Y and Zhao, D and Xu, D and Lian, X and Fang, L and Yu, Y and Liao, X and Liu, Y and Sun, J},
title = {Exposure to salinomycin dysregulates interplay between mitophagy and oxidative response to damage the porcine jejunal cells.},
journal = {The Science of the total environment},
volume = {900},
number = {},
pages = {166441},
doi = {10.1016/j.scitotenv.2023.166441},
pmid = {37604367},
issn = {1879-1026},
abstract = {Salinomycin (SAL) has caused widespread pollution as a feed additive and growth promoter in livestock such as pigs, exerting a negative impact on public health. The toxicity mechanism of SAL has been widely studied in chickens, but the underlying mechanisms of SAL-induced toxicity to pigs and the ecosystem remain undefined. In this study, we explored the potential damage of SAL in IPEC-J2 cells to identify the effects of excessive SAL on the interplay between mitophagy and oxidative stress. The results showed that a concentration-dependent response was observed for SAL in altering cellular morphology and inducing cell death in IPEC-J2 cells, including the induction of cell cycle arrest and lactic dehydrogenase (LDH) release. Meanwhile, we found that excessive SAL led to oxidative damage by activating the Nrf2/Keap1/HO-1 pathway, accompanied by reactive oxygen species (ROS) elevation and the reduction of antioxidant enzyme activity. We also found that PINK1/Parkin-dependent mitophagy was activated by SAL exposure, particularly with mitochondrial membrane potential reduction. Interestingly, SAL-induced oxidative damages were prevented after the autophagy inhibitor 3-methyladenine (3-MA) treatment, and mitophagy was alleviated following ROS scavenger (N-acetylcysteine, NAC) treatment. Overall, our findings showed that SAL stimulated oxidative stress and mitophagy in IPEC-J2 cells resulting in cellular injury, and there was a strong connection between SAL-induced oxidative stress and mitophagy. Targeting ROS/PINK1/Parkin-dependent mitophagy and oxidative stress could be a novel protective mechanism in SAL-induced cell damage.},
}

@article {pmid37598316,
year = {2023},
author = {Etemadi, Y and Akakpo, JY and Ramachandran, A and Jaeschke, H},
title = {Nrf2 as a therapeutic target in acetaminophen hepatotoxicity: A case study with sulforaphane.},
journal = {Journal of biochemical and molecular toxicology},
volume = {},
number = {},
pages = {e23505},
doi = {10.1002/jbt.23505},
pmid = {37598316},
issn = {1099-0461},
support = {R01 DK102142/DK/NIDDK NIH HHS/United States ; DK125465/DK/NIDDK NIH HHS/United States ; P20 GM103549/GM/NIGMS NIH HHS/United States ; P30 GM118247/GM/NIGMS NIH HHS/United States ; },
abstract = {Acetaminophen (APAP) overdose can cause severe liver injury and acute liver failure. The only clinically approved antidote, N-acetylcysteine (NAC), is highly effective but has a narrow therapeutic window. In the last 2 decades, activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates acute phase proteins and antioxidant defense genes, has emerged as a putative new therapeutic target against APAP hepatotoxicity. However, virtually all studies that propose Nrf2 activation as mechanism of protection used prolonged pretreatment, which is not a clinically feasible approach to treat a drug overdose. Therefore, the objective of this study was to assess if therapeutic activation of Nrf2 is a viable approach to treat liver injury after APAP overdose. We used the water-soluble Nrf2 activator sulforaphane (SFN; 5 mg/kg) in a murine model of APAP hepatotoxicity (300 mg/kg). Our results indicate that short-term treatment (≤3 h) with SFN alone did not activate Nrf2 or its target genes. However, posttreatment with SFN after APAP partially protected at 6 h likely due to more rapid activation of the Nrf2-target gene heme oxygenase-1. A direct comparison of SFN with NAC given at 1 h after APAP showed a superior protection with NAC, which was maintained at 24 h unlike with SFN. Thus, Nrf2 activators have inherent problems like the need to create a cellular stress to activate Nrf2 and delayed adaptive responses which may hamper sustained protection against APAP hepatotoxicity. Thus, compared to the more direct acting antidote NAC, Nrf2 activators are less suitable for this indication.},
}

@article {pmid37596428,
year = {2023},
author = {Clark, RSB and Empey, PE and Kochanek, PM and Bell, MJ},
title = {N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {},
pmid = {37596428},
issn = {1878-7479},
support = {R01 NS069247/NS/NINDS NIH HHS/United States ; },
abstract = {N-Acetylcysteine (NAC) has shown promise as a putative neurotherapeutic for traumatic brain injury (TBI). Yet, many such promising compounds have limited ability to cross the blood-brain barrier (BBB), achieve therapeutic concentrations in brain, demonstrate target engagement, among other things, that have hampered successful translation. A pharmacologic strategy for overcoming poor BBB permeability and/or efflux out of the brain of organic acid-based, small molecule therapeutics such as NAC is co-administration with a targeted or nonselective membrane transporter inhibitor. Probenecid is a classic ATP-binding cassette and solute carrier inhibitor that blocks transport of organic acids, including NAC. Accordingly, combination therapy using probenecid as an adjuvant with NAC represents a logical neurotherapeutic strategy for treatment of TBI (and other CNS diseases). We have completed a proof-of-concept pilot study using this drug combination in children with severe TBI-the Pro-NAC Trial (ClinicalTrials.gov NCT01322009). In this review, we will discuss the background and rationale for combination therapy with probenecid and NAC in TBI, providing justification for further clinical investigation.},
}

@article {pmid37595880,
year = {2023},
author = {Yang, L and Mei, G and Yang, Y and Cui, J and Peng, S and Peng, Z and Cheng, Y},
title = {Hexachlorocyclohexane impairs human sperm motility by affecting lysine glutarylation and mitochondrial functions.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {179},
number = {},
pages = {113991},
doi = {10.1016/j.fct.2023.113991},
pmid = {37595880},
issn = {1873-6351},
mesh = {Humans ; Male ; *Hexachlorocyclohexane ; *Lysine ; Reactive Oxygen Species ; Sperm Motility ; Semen ; Acetylcysteine ; Mitochondria ; },
abstract = {Decreased sperm motility is a leading cause of male infertility and persistent organic pollutants are known to contribute significantly to the development of this disease. The effects of organochlorine pesticides such as hexachlorocyclohexane (HCH) on human sperm function and their mechanisms of action have received much attention, but are still not fully understood. Herein, we discovered that HCH has a concentration- and time-dependent inhibitory effect on human sperm motility in vitro. Moreover, HCH could reduce the levels of lysine glutarylation (Kglu) and glucose-6-phosphate dehydrogenase activity in sperm. Meanwhile, HCH could increase reactive oxygen species and thereby lead to mitochondrial depolarization and the down-regulation of adenosine triphosphate levels. In particular, we observed that sodium glutarate (Na-glu), the precursor of glutaryl-CoA, could alleviate the inhibitory effect of HCH on sperm Kglu levels, whereas the ROS scavenger N-acetyl-L-cysteine (NAC) had no effect. Intriguingly, both Na-glu and NAC were able to partially inhibit the HCH-induced increase in sperm ROS levels and impaired sperm motility. In conclusion, we propose that HCH inhibits sperm Kglu, leading to the disruption of mitochondrial energy metabolism, which in turn adversely affects sperm motility.},
}

Humans
Male
*Hexachlorocyclohexane
*Lysine
Reactive Oxygen Species
Sperm Motility
Semen
Acetylcysteine
Mitochondria

@article {pmid37595477,
year = {2023},
author = {Zhu, X and Song, Y and Wang, X and Zhou, Y and Chai, Y and Yuan, R},
title = {Copper nanoclusters electrochemiluminescence with tunable near-infrared emission wavelength for ultrasensitive detection of matrix metalloproteinase-2.},
journal = {Biosensors & bioelectronics},
volume = {238},
number = {},
pages = {115580},
doi = {10.1016/j.bios.2023.115580},
pmid = {37595477},
issn = {1873-4235},
mesh = {Humans ; *Copper ; Matrix Metalloproteinase 2 ; *Biosensing Techniques ; Methionine ; Racemethionine ; Acetylcysteine ; },
abstract = {Herein, the methionine (Met)/N-acetyl-L-cysteine (NAC) templated copper nanoclusters (Met/NAC-Cu NCs) with tunable near-infrared region (NIR) electrochemiluminescence (ECL) emission wavelength was firstly synthesized as emitter for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2). Significantly, the NAC played the role of template and reductant of cupric to acquire Cu NCs, and the surface defect regulator Met was used to connect NAC through -S-S- bond, which could heighten the surface defect of Cu NCs to continuously regulate the maximum ECL emission by successively controlling the molar ratio of Met and NAC, leading to the ECL emission wavelength of Cu NCs ranged from 680 nm to 750 nm. In addition, a rapid target triggered catalyst hairpin assembly (CHA) recycling amplification strategy was constructed through orderly and equidistantly arranging hairpin to increase its local concentration, resulting in greatly accelerated signal amplification efficiency and reaction rate. As a proof of concept, based on Met/NAC-Cu NCs as NIR ECL emitter and effective signal amplification tactic, a super-sensitive ECL biosensor was fabricated to detect target MMP-2 with the detection limit (LOD) as low as 1.65 fg/mL and successfully utilized for detecting of MMP-2 that from Hela and MCF-7 cancer cells. This research provided a wonderful avenue for regulating the optical performance of metal nanoclusters-based ECL emitters, and the developed neoteric NIR ECL emitter with the merits of less photochemical damage and deeper tissue penetration exhibited great potential in ultrasensitive biosensing and high-definition ECL imaging.},
}

Humans
*Copper
Matrix Metalloproteinase 2
*Biosensing Techniques
Methionine
Racemethionine
Acetylcysteine

@article {pmid37594415,
year = {2023},
author = {Le-Vinh, B and Steinbring, C and Nguyen Le, NM and Matuszczak, B and Bernkop-Schnürch, A},
title = {S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.},
journal = {ACS applied materials & interfaces},
volume = {15},
number = {34},
pages = {40304-40316},
pmid = {37594415},
issn = {1944-8252},
mesh = {*Chitosan ; Biocompatible Materials/pharmacology ; Tissue Engineering ; Acetylcysteine ; Carbodiimides ; Cryogels ; },
abstract = {Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio) propanoic acid was covalently attached to Ch via a carbodiimide-mediated reaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2, and Ch-SS-3) with 54, 107 and 140 μmol of ligand per gram of polymer, respectively, were tested. In parallel, three thiolated Chs, namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modification to compare the effectiveness of disulfide versus thiol modification on cell adhesion. Ch-SS-1 showed better cell adhesion capability than Ch-SS-2 and Ch-SS-3. This can be explained by the more lipophilic surfaces of Ch-SS as a higher modification was made. Although Ch-SH-1, Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion, growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymers in the formation of 3D cell cultures. Cryogels structured by Ch-SS-1 (SSg) resulted in homogeneous scaffolds with tunable pore size and mechanical properties by changing the mass ratio between Ch-SS-1 and heparin used as a cross-linker. SSg scaffolds possessing interconnected microporous structures showed good cell migration, adhesion, and proliferation. Therefore, Ch-SS can be used to construct tunable cryogel scaffolds that are suitable for 3D cell culture and TE.},
}

*Chitosan
Biocompatible Materials/pharmacology
Tissue Engineering
Acetylcysteine
Carbodiimides
Cryogels

@article {pmid37591474,
year = {2023},
author = {Singh, S and Wairkar, S},
title = {Long-circulating thiolated chitosan nanoparticles of nintedanib with N-acetyl cysteine for treating idiopathic pulmonary fibrosis: In vitro assessment of cytotoxicity, antioxidant, and antifibrotic potential.},
journal = {International journal of pharmaceutics},
volume = {644},
number = {},
pages = {123322},
doi = {10.1016/j.ijpharm.2023.123322},
pmid = {37591474},
issn = {1873-3476},
mesh = {Humans ; Antioxidants/pharmacology ; Acetylcysteine ; *Chitosan ; *Idiopathic Pulmonary Fibrosis/drug therapy ; },
abstract = {Nintedanib (NIN) is one of the FDA-approved tyrosine kinase inhibitor drugs used to treat idiopathic pulmonary fibrosis (IPF). This study aimed to formulate a long-circulating injection of Nintedanib to treat bedridden patients with IPF. Nintedanib was incorporated into chitosan nanoparticles (NIN-NP) via the ionic gelation method, and N-acetyl cysteine (NAC), a known antioxidant and mucolytic agent, was added to the NIN-NP (NAC-NIN-NP). The lyophilized formulation had a particle size of 174 nm, a polydispersity index of 0.511, and a zeta potential of 18.6 mV. The spherical nanoparticles were observed in transmission electron microscopy, whereas field emission scanning electron microscopy showed irregular clusters of NP. The thiolation of the chitosan in NAC-NIN-NP was confirmed by ATR-FTIR and NMR, which improved drug release profiles showing >90 % drug release that was 2.42-folds greater than NIN-NP lasting for five days. The DPPH assay showed that adding NAC increased the % inhibition of oxidation in blank-NP (from 54.59 % to 87.17 %) and NIN-NP (58.65 %-89.19 %). The MTT assay on A549 cells showed 67.57 % cell viability by NAC-NIN-NP with an IC50 value of 28 μg/mL. The NAC formulation reduced hydroxyproline content (56.77 μg/mL) compared to NIN-NP (69.48 μg/mL) in WI-38 cell lines. Meanwhile, the healthy cells count with NAC-NIN-NP was higher (5.104 × 10[3]) than with NIN-NP (4.878 × 10[3]). In Hoechst staining, no significant damage to DNA was observed by the drug or formulation. Therefore, NAC-NIN-NP could be a promising treatment option for IPF patients and can be studied further clinically.},
}

Humans
Antioxidants/pharmacology
Acetylcysteine
*Chitosan
*Idiopathic Pulmonary Fibrosis/drug therapy

@article {pmid37580920,
year = {2023},
author = {Niloufar Darbandi, - and Samira Moghadasi, - and Hamid Reza Momeni, - and Matin Ramezani, -},
title = {Comparing the acute and chronic effects of metformin and antioxidant protective effects of N-acetyl cysteine on memory retrieval and oxidative stress in rats with Alzheimer's disease.},
journal = {Pakistan journal of pharmaceutical sciences},
volume = {36},
number = {3},
pages = {731-739},
pmid = {37580920},
issn = {1011-601X},
mesh = {Rats ; Animals ; Antioxidants/pharmacology ; Acetylcysteine/pharmacology ; *Alzheimer Disease/chemically induced/drug therapy ; *Metformin/pharmacology ; Oxidative Stress ; Streptozocin/pharmacology ; Disease Models, Animal ; Maze Learning ; },
abstract = {It has been suggested that oxidative stress plays an important role in neural degeneration and Alzheimer's disease. Some studies have shown that metformin has some beneficial effects on the brain and reduces oxidative stress, while others reveal that metformin increases oxidative stress in diabetic patients. In this study acute and chronic effects of metformin and antioxidant protective effects of N-acetyl cysteine in Alzheimeric rats were investigated. Animals were divided into seven groups (n=8): Control, STZ, STZ + metformin (one, three and eleven weeks), STZ+ metformin (eleven weeks) +N-acetyl cysteine (eleven weeks) and N-acetyl cysteine (eleven weeks). ICV injections of saline (1μl/rat) or STZ (3mg/kg) and IP injections of Saline (1ml/kg), metformin (200mg/kg) and/or N-acetyl cysteine (100mg/kg) were done. Memory retrieval, CA1 neurons density and serums oxidative stress were investigated. STZ injections reduced memory retention, intact neurons and increased serum oxidative stress compared to the control (p<0/001). Metformin injection for one and three weeks (but not eleven weeks) improved the effects of STZ (p<0/001). Administration of N-acetylcysteine with metformin (eleven weeks) improved STZ bad effects (p<0/001). It seems that acute and chronic consumption of metformin have different effects on memory retrieval, CA1 neurons and serum oxidative stress factors in AD rats.},
}

Rats
Animals
Antioxidants/pharmacology
Acetylcysteine/pharmacology
*Alzheimer Disease/chemically induced/drug therapy
*Metformin/pharmacology
Oxidative Stress
Streptozocin/pharmacology
Disease Models, Animal
Maze Learning

@article {pmid37579929,
year = {2023},
author = {Kolomaznik, M and Hanusrichterova, J and Mikolka, P and Kosutova, P and Vatecha, M and Zila, I and Mokra, D and Calkovska, A},
title = {Efficiency of exogenous surfactant combined with intravenous N-acetylcysteine in two-hit rodent model of ARDS.},
journal = {Respiratory physiology & neurobiology},
volume = {316},
number = {},
pages = {104138},
doi = {10.1016/j.resp.2023.104138},
pmid = {37579929},
issn = {1878-1519},
mesh = {Rats ; Animals ; Acetylcysteine/pharmacology/therapeutic use ; *Lung Injury ; Antioxidants/pharmacology/therapeutic use ; Surface-Active Agents ; Rodentia ; *Hyperoxia ; Rats, Wistar ; Lung ; *Pulmonary Surfactants/pharmacology ; *Respiratory Distress Syndrome ; },
abstract = {Accumulation of reactive oxygen species during hyperoxia together with secondary bacteria-induced inflammation leads to lung damage in ventilated critically ill patients. Antioxidant N-acetylcysteine (NAC) in combination with surfactant may improve lung function. We compared the efficacy of NAC combined with surfactant in the double-hit model of lung injury. Bacterial lipopolysaccharide (LPS) instilled intratracheally and hyperoxia were used to induce lung injury in Wistar rats. Animals were mechanically ventilated and treated intravenously with NAC alone or in combination with intratracheal surfactant (poractant alfa; PSUR+NAC). Control received saline. Lung functions, inflammatory markers, oxidative damage, total white blood cell (WBC) count and lung oedema were evaluated during 4 hrs. Administration of NAC increased total antioxidant capacity (TAC) and decreased IL-6. This effect was potentiated by the combined administration of surfactant and NAC. In addition, PSUR+NAC reduced the levels of TNFα, IL-1ß, and TAC compared to NAC only and improved lung injury score. The combination of exogenous surfactant with NAC suppresses lung inflammation and oxidative stress in the experimental double-hit model of lung injury.},
}

Rats
Animals
Acetylcysteine/pharmacology/therapeutic use
*Lung Injury
Antioxidants/pharmacology/therapeutic use
Surface-Active Agents
Rodentia
*Hyperoxia
Rats, Wistar
Lung
*Pulmonary Surfactants/pharmacology
*Respiratory Distress Syndrome

@article {pmid37577725,
year = {2023},
author = {da Paz Martins, AS and de Andrade, KQ and de Araújo, ORP and da Conceição, GCM and da Silva Gomes, A and Goulart, MOF and Moura, FA},
title = {Extraintestinal Manifestations in Induced Colitis: Controversial Effects of N-Acetylcysteine on Colon, Liver, and Kidney.},
journal = {Oxidative medicine and cellular longevity},
volume = {2023},
number = {},
pages = {8811463},
pmid = {37577725},
issn = {1942-0994},
mesh = {Humans ; Male ; Mice ; Animals ; Acetylcysteine/pharmacology/therapeutic use/metabolism ; Interleukin-10/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Hydrogen Peroxide/pharmacology ; Glutathione Disulfide/metabolism ; *Colitis/chemically induced/complications/drug therapy ; Colon ; *Colitis, Ulcerative/chemically induced/drug therapy/pathology ; Antioxidants/pharmacology ; Inflammation/pathology ; Oxidative Stress ; Liver/metabolism ; Glutathione/metabolism ; Superoxide Dismutase/metabolism ; Dextran Sulfate/toxicity ; },
abstract = {Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N-acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38[th] day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H2O2)) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF-α, and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF-α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease.},
}

Humans
Male
Mice
Animals
Acetylcysteine/pharmacology/therapeutic use/metabolism
Interleukin-10/metabolism
Tumor Necrosis Factor-alpha/metabolism
Hydrogen Peroxide/pharmacology
Glutathione Disulfide/metabolism
*Colitis/chemically induced/complications/drug therapy
Colon
*Colitis, Ulcerative/chemically induced/drug therapy/pathology
Antioxidants/pharmacology
Inflammation/pathology
Oxidative Stress
Liver/metabolism
Glutathione/metabolism
Superoxide Dismutase/metabolism
Dextran Sulfate/toxicity

@article {pmid37575813,
year = {2023},
author = {Le, D and Hydro, BA and Jones, CL and Beauchamp, GA},
title = {Weight Loss or Liver Loss: A Case Report on Fulminant Hepatic Failure Secondary to Garcinia cambogia Supplementation.},
journal = {Cureus},
volume = {15},
number = {7},
pages = {e41778},
pmid = {37575813},
issn = {2168-8184},
abstract = {This case describes a 56-year-old man with a past medical history including sickle cell trait requiring blood transfusions, who presented to the emergency department (ED) with generalized weakness and fatigue following Garcinia cambogia supplementation. Initial laboratory abnormalities included: aspartate aminotransferase (AST) and alanine transaminase (ALT) 4,222 U/L and 4,664 U/L respectively, alkaline phosphatase 215 U/L, international normalized ratio (INR) 3.2, and his model for end-stage liver disease was 37. Creatinine, hemoglobin and hematocrit, and ferritin levels were all elevated. The differential diagnosis for his acute illness was broad ranging from hemochromatosis, anabolic steroid use, and portal venous thrombosis. The patient was started on N-acetylcysteine (NAC) and his liver function improved. He was discharged on hospital day 10 and instructed to discontinue his supplements and follow up for repeat blood work. This case explores the critical management of G. cambogia toxicity. The patient explored G. cambogia as an herbal supplementation resulting in weight loss, worsening generalized fatigue, and fulminant hepatic failure.},
}

@article {pmid37575276,
year = {2023},
author = {Tanomrat, R and Naktubtim, C and Aimvijarn, P and Suwannalert, P},
title = {N-acetylcysteine improves the inhibitory effect of Quercetin-rich onion extract on HT-29 and HCT-116 colorectal cancer migration and invasion through iNOS suppression.},
journal = {International journal of medical sciences},
volume = {20},
number = {9},
pages = {1123-1134},
pmid = {37575276},
issn = {1449-1907},
mesh = {Humans ; Acetylcysteine/pharmacology/therapeutic use ; *Antineoplastic Agents/pharmacology/therapeutic use ; Antioxidants/pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; *Colorectal Neoplasms/drug therapy/genetics/metabolism ; Glutathione/pharmacology ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2/genetics ; Onions ; Quercetin/pharmacology/therapeutic use ; },
abstract = {As colorectal cancer (CRC) usually presents at an advanced stage, it responds poorly to traditional surgery and chemoradiotherapy. Reactive oxygen species (ROSs) are a critical factor in cancer progression. Quercetin, a bioflavonoid derived from onion peel extract, provides great anti-oxidant and anti-cancer potential. Therefore, quercetin in combination with N-Acetylcysteine (NAC), a well-known anti-oxidant and adjuvant agent in cancer-chemotherapeutic drugs, was considered as a way of increasing treatment efficacy. Thus, this study aimed to evaluate the improvement effect of quercetin in combination with NAC in human CRC (HT-29 and HCT-116) cell progression, migration and invasion. Firstly, the effects of quercetin, NAC, and the combination of quercetin and NAC on cellular oxidants and glutathione levels were evaluated. Cell viability, anti-migrative activity and invasive activity were determined by MTT, wound healing, and Matrigel invasion tests, respectively. Then, the proteins involved in cell migration, invasion, and cellular oxidants were investigated. Moreover, the gene expression and overall survival were further validated by the GEPIA2 database. The results reveal that the combination was most effective in decreasing cellular oxidants and increasing glutathione levels, while there was a significant decrease in cancer cell migration and invasion involved in the suppression of iNOS, ICAM-1, and MMP-2 proteins. Furthermore, bioinformatic analysis verified that iNOS, ICAM-1, and MMP-2 were highly expressed in CRC tissue and also associated with a poor prognosis. This study demonstrated that Quercetin has higher efficacy when used in combination with NAC, representing a potential combination agent for anti-cancer drug development.},
}

Humans
Acetylcysteine/pharmacology/therapeutic use
*Antineoplastic Agents/pharmacology/therapeutic use
Antioxidants/pharmacology/therapeutic use
Cell Line, Tumor
Cell Movement
Cell Proliferation
*Colorectal Neoplasms/drug therapy/genetics/metabolism
Glutathione/pharmacology
Intercellular Adhesion Molecule-1
Matrix Metalloproteinase 2/genetics
Onions
Quercetin/pharmacology/therapeutic use

@article {pmid37573526,
year = {2023},
author = {Rasaeifar, K and Zavareh, S and Hajighasem-Kashani, M and Nasiri, M},
title = {Effects of pulsed electromagnetic fields and N-acetylcysteine on transplantation of vitrified mouse ovarian tissue.},
journal = {Electromagnetic biology and medicine},
volume = {42},
number = {2},
pages = {67-80},
doi = {10.1080/15368378.2023.2246503},
pmid = {37573526},
issn = {1536-8386},
mesh = {Mice ; Female ; Animals ; *Acetylcysteine/pharmacology ; *Tumor Necrosis Factor-alpha/genetics ; Electromagnetic Fields ; Fibroblast Growth Factor 2 ; Interleukin-6 ; Vascular Endothelial Growth Factor A/genetics ; Antioxidants/pharmacology/metabolism ; },
abstract = {In this experimental study, adult female NMRI mice were randomly assigned to five groups: control ;(fresh ovarian transplantation, OT); sham ;(vitrified OT); NAC ;(vitrified OT treated with N-acetyl cysteine, NAC); EMF ;(vitrified OT treated with pulsed electromagnetic fields, PEMF); and NAC+EMF ;(vitrified OT combined with NAC and PEMF). We conducted histological assessments to evaluate follicle reservation and vascularization. Furthermore, we examined the relative expression of Fgf-2, Vegf, Tnf-α, Il-6, Il-1, and Cd31 genes on days 2 and 7 after OT. Additionally, we measured total antioxidant capacity (TAC), malondialdehyde (MDA) levels, as well as the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Our results demonstrated that NAC, PEMF, and NAC+PEMF treatments significantly increased the number of follicles. Moreover, we observed a more pronounced development of vascularization in the NAC, PEMF, and PEMF+NAC groups. The relative expression levels of Fgf-2, Vegf, Tnf-α, Il-1β, and Il-6 were significantly elevated in the NAC, PEMF, and NAC+PEMF groups. Notably, TAC levels decreased significantly in the NAC group compared to the control group. Additionally, the MDA level showed a significant decrease in the PEMF+NAC group when compared to the other groups. Overall, the combination of NAC and PEMF exhibited a synergistic effect in promoting angiogenesis and protecting against oxidative stress and inflammation during OT.},
}

Mice
Female
Animals
*Acetylcysteine/pharmacology
*Tumor Necrosis Factor-alpha/genetics
Electromagnetic Fields
Fibroblast Growth Factor 2
Interleukin-6
Vascular Endothelial Growth Factor A/genetics
Antioxidants/pharmacology/metabolism

@article {pmid37572985,
year = {2023},
author = {Kim, D and Oh, E and Kim, H and Baek, SM and Cho, J and Kim, EH and Choi, S and Bian, Y and Kim, W and Bae, ON},
title = {Mono-(2-ethylhexyl)-phthalate potentiates methylglyoxal-induced blood-brain barrier damage via mitochondria-derived oxidative stress and bioenergetic perturbation.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {179},
number = {},
pages = {113985},
doi = {10.1016/j.fct.2023.113985},
pmid = {37572985},
issn = {1873-6351},
mesh = {Rats ; Animals ; *Diethylhexyl Phthalate/toxicity ; Pyruvaldehyde ; Blood-Brain Barrier/metabolism ; Endothelial Cells/metabolism ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism ; },
abstract = {Phthalates in contaminated foods and personal care products are one of the most frequently exposed chemicals with a public health concern. Phthalate exposure is related to cardiovascular diseases, including diabetic vascular complications and cerebrovascular diseases, yet the mechanism is still unclear. The blood-brain barrier (BBB) integrity disruption is strongly associated with cardiovascular and neurological disease exacerbation. We investigated BBB damage by di-(2-ethylhexyl) phthalate (DEHP) or its metabolite mono-(2-ethylhexyl) phthalate (MEHP) using brain endothelial cells and rat models. BBB damage by the subthreshold level of MEHP, but not a DEHP, significantly increased by the presence of methylglyoxal (MG), a reactive dicarbonyl compound whose levels increase in the blood in hyperglycemic conditions in diabetic patients. Significant potentiation in apoptosis and autophagy activation, mitochondria-derived reactive oxygen species (ROS) production, and mitochondrial metabolic disturbance were observed in brain ECs by co-exposure to MG and MEHP. N-acetyl cysteine (NAC) restored autophagy activation as well as tight junction protein impairment induced by co-exposure to MG and MEHP. Intraperitoneal administration of MG and MEHP significantly altered mitochondrial membrane potential and tight junction integrity in rat brain endothelium. This study may provide novel insights into enhancing phthalate toxicity in susceptible populations, such as diabetic patients.},
}

Rats
Animals
*Diethylhexyl Phthalate/toxicity
Pyruvaldehyde
Blood-Brain Barrier/metabolism
Endothelial Cells/metabolism
Oxidative Stress
Energy Metabolism
Mitochondria/metabolism

@article {pmid37569897,
year = {2023},
author = {Khashab, R and Gutman-Sharabi, N and Shabtai, Z and Landau, R and Halperin, R and Fay-Karmon, T and Leibowitz, A and Sharabi, Y},
title = {Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson's Disease.},
journal = {International journal of molecular sciences},
volume = {24},
number = {15},
pages = {},
pmid = {37569897},
issn = {1422-0067},
mesh = {Rats ; Animals ; *Parkinson Disease/drug therapy/etiology/metabolism ; Rotenone/pharmacology ; Dopamine/metabolism ; Selegiline ; Aldehyde Dehydrogenase/metabolism ; Monoamine Oxidase Inhibitors/pharmacology ; Acetylcysteine/pharmacology ; },
abstract = {The catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease centers on accumulation of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in dopaminergic neurons. To test the hypothesis, it is necessary to reduce DOPAL and assess if this improves locomotor abnormalities. Systemic administration of rotenone to rats reproduces the motor and central neurochemical abnormalities characterizing Parkinson's disease. In this study, we used the monoamine oxidase inhibitor (MAOI) deprenyl to decrease DOPAL production, with or without the antioxidant N-acetylcysteine (NAC). Adult rats received subcutaneous vehicle, rotenone (2 mg/kg/day via a minipump), or rotenone with deprenyl (5 mg/kg/day i.p.) with or without oral NAC (1 mg/kg/day) for 28 days. Motor function tests included measures of open field activity and rearing. Striatal tissue was assayed for contents of dopamine, DOPAL, and other catechols. Compared to vehicle, rotenone reduced locomotor activity (distance, velocity and rearing); increased tissue DOPAL; and decreased dopamine concentrations and inhibited vesicular sequestration of cytoplasmic dopamine and enzymatic breakdown of cytoplasmic DOPAL by aldehyde dehydrogenase (ALDH), as indicated by DA/DOPAL and DOPAC/DOPAL ratios. The addition of deprenyl to rotenone improved all the locomotor indices, increased dopamine and decreased DOPAL contents, and corrected the rotenone-induced vesicular uptake and ALDH abnormalities. The beneficial effects were augmented when NAC was added to deprenyl. Rotenone evokes locomotor and striatal neurochemical abnormalities found in Parkinson's disease, including DOPAL buildup. Administration of an MAOI attenuates these abnormalities, and NAC augments the beneficial effects. The results indicate a pathogenic role of DOPAL in the rotenone model and suggest that treatment with MAOI+NAC might be beneficial for Parkinson's disease treatment.},
}

Rats
Animals
*Parkinson Disease/drug therapy/etiology/metabolism
Rotenone/pharmacology
Dopamine/metabolism
Selegiline
Aldehyde Dehydrogenase/metabolism
Monoamine Oxidase Inhibitors/pharmacology
Acetylcysteine/pharmacology

@article {pmid37569463,
year = {2023},
author = {Pieri, BLDS and Rodrigues, MS and Farias, HR and Silveira, GB and Ribeiro, VSGDC and Silveira, PCL and De Souza, CT},
title = {Role of Oxidative Stress on Insulin Resistance in Diet-Induced Obesity Mice.},
journal = {International journal of molecular sciences},
volume = {24},
number = {15},
pages = {},
pmid = {37569463},
issn = {1422-0067},
abstract = {Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.},
}

@article {pmid37569345,
year = {2023},
author = {Kang, M and Kang, JH and Sim, IA and Seong, DY and Han, S and Jang, H and Lee, H and Kang, SW and Kim, SY},
title = {Glucose Deprivation Induces Cancer Cell Death through Failure of ROS Regulation.},
journal = {International journal of molecular sciences},
volume = {24},
number = {15},
pages = {},
pmid = {37569345},
issn = {1422-0067},
support = {NRF- 2019M3A9G1104345//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Glucose/metabolism ; Reactive Oxygen Species/metabolism ; Antioxidants ; NADP/metabolism ; Cell Death ; Glutathione/metabolism ; *Neoplasms/metabolism ; Adenosine Triphosphate/metabolism ; },
abstract = {In previous work, we showed that cancer cells do not depend on glycolysis for ATP production, but they do on fatty acid oxidation. However, we found some cancer cells induced cell death after glucose deprivation along with a decrease of ATP production. We investigated the different response of glucose deprivation with two types of cancer cells including glucose insensitive cancer cells (GIC) which do not change ATP levels, and glucose sensitive cancer cells (GSC) which decrease ATP production in 24 h. Glucose deprivation-induced cell death in GSC by more than twofold after 12 h and by up to tenfold after 24 h accompanied by decreased ATP production to compare to the control (cultured in glucose). Glucose deprivation decreased the levels of metabolic intermediates of the pentose phosphate pathway (PPP) and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) in both GSC and GIC. However, glucose deprivation increased reactive oxygen species (ROS) only in GSC, suggesting that GIC have a higher tolerance for decreased NADPH than GSC. The twofold higher ratio of reduced/oxidized glutathione (GSH/GSSG) in GIS than in GSC correlates closely with the twofold lower ROS levels under glucose starvation conditions. Treatment with N-acetylcysteine (NAC) as a precursor to the biologic antioxidant glutathione restored ATP production by 70% and reversed cell death caused by glucose deprivation in GSC. The present findings suggest that glucose deprivation-induced cancer cell death is not caused by decreased ATP levels, but rather triggered by a failure of ROS regulation by the antioxidant system. Conclusion is clear that glucose deprivation-induced cell death is independent from ATP depletion-induced cell death.},
}

Humans
*Glucose/metabolism
Reactive Oxygen Species/metabolism
Antioxidants
NADP/metabolism
Cell Death
Glutathione/metabolism
*Neoplasms/metabolism
Adenosine Triphosphate/metabolism

@article {pmid37567958,
year = {2023},
author = {Bhattacharya, R and Saini, S and Ghosh, S and Roy, P and Ali, N and Parvez, MK and Al-Dosari, MS and Mishra, AK and Singh, LR},
title = {Organosulfurs, S-allyl cysteine and N-acetyl cysteine sequester di-carbonyls and reduces carbonyl stress in HT22 cells.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {13071},
pmid = {37567958},
issn = {2045-2322},
mesh = {*Acetylcysteine/pharmacology ; *Cysteine/metabolism ; Glycation End Products, Advanced/metabolism ; Antioxidants/pharmacology ; Maillard Reaction ; },
abstract = {Diabetes, characterized by high blood glucose level, is a progressive metabolic disease that leads to serious health complications. One of the major pathological consequences associated with diabetes is the accumulation of highly reactive carbonyl compounds called advanced glycation end products (AGEs). Most of the AGEs are dicarbonyls and have the potential to covalently modify proteins especially at the lysine residues in a non-enzymatic fashion (a process termed as glycation) resulting in the functional impairment and/or toxic gain in function. Therefore, non-toxic small molecules that can inhibit glycation are of interest for the therapeutic intervention of diabetes. In the present communication, we have investigated the effect of organosulfurs (S-allyl cysteine, SAC and N-acetyl cysteine, NAC) that are major principal components of Allium sativa against the glycation of different proteins. We discovered that both SAC and NAC are potent anti-glycating agents. We also found that both SAC and NAC reduce ROS level and inhibit apoptosis caused by protein glycation.},
}

*Acetylcysteine/pharmacology
*Cysteine/metabolism
Glycation End Products, Advanced/metabolism
Antioxidants/pharmacology
Maillard Reaction

@article {pmid37567916,
year = {2023},
author = {Naushad, SM and Mandadapu, G and Ramaiah, MJ and Almajhdi, FN and Hussain, T},
title = {The role of TLR7 agonists in modulating COVID-19 severity in subjects with loss-of-function TLR7 variants.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {13078},
pmid = {37567916},
issn = {2045-2322},
mesh = {Male ; Humans ; *Toll-Like Receptor 7/genetics/metabolism ; Myeloid Differentiation Factor 88/genetics/metabolism ; RNA, Viral ; *COVID-19/genetics ; SARS-CoV-2/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adjuvants, Immunologic ; },
abstract = {We investigate the mechanism associated with the severity of COVID-19 in men with TLR7 mutation. Men with loss-of-function (LOF) mutations in TLR7 had severe COVID-19. LOF mutations in TLR7 increased the risk of critical COVID by 16.00-fold (95% confidence interval 2.40-106.73). The deleterious mutations affect the binding of SARS-CoV2 RNA (- 328.66 ± 26.03 vs. - 354.08 ± 27.70, p = 0.03) and MYD88 (β: 40.279, p = 0.003) to TLR7 resulting in the disruption of TLR7-MyD88-TIRAP complex. In certain hypofunctional variants and all neutral/benign variants, there is no disruption of TLR7-MyD88-TIRAP complex and four TLR7 agonists showed binding affinity comparable to that of wild protein. N-acetylcysteine (NAC) also showed a higher binding affinity for the LOF variants (p = 0.03). To conclude, TLR7 LOF mutations increase the risk of critical COVID-19 due to loss of viral RNA sensing ability and disrupted MyD88 signaling. Majority of hypofunctional and neutral variants of TLR7 are capable of carrying MyD88 signaling by binding to different TLR7 agonists and NAC.},
}

Male
Humans
*Toll-Like Receptor 7/genetics/metabolism
Myeloid Differentiation Factor 88/genetics/metabolism
RNA, Viral
*COVID-19/genetics
SARS-CoV-2/genetics
Adaptor Proteins, Signal Transducing/metabolism
Adjuvants, Immunologic

@article {pmid37567457,
year = {2023},
author = {Zheng, X and Su, F and Lei, M and Li, J and Zhang, C and Zhang, Y and Wei, M and Li, W and Chen, S and Liu, Y and Gao, Q and Hao, L},
title = {The novel peptide athycaltide-1 attenuates Ang II-induced pathological myocardial hypertrophy by reducing ROS and inhibiting the activation of CaMKII and ERK1/2.},
journal = {European journal of pharmacology},
volume = {957},
number = {},
pages = {175969},
doi = {10.1016/j.ejphar.2023.175969},
pmid = {37567457},
issn = {1879-0712},
abstract = {Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology. The results showed that the differentially expressed genes (DEGs) were significantly enriched in cell response to oxidative stress, regulation of reactive oxygen species metabolism and calmodulin binding. Then, the oxidation level of mouse hearts and H9c2 cardiomyocytes in each group and the expression of key proteins of CaMKII/HDAC/MEF2C and ERK1/2 signaling pathways were detected to preliminarily verify the positive effect of ATH-1. At the same time, the effect of ATH-1 was further determined by adding reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) and CaMKII inhibitor AIP in vitro. The results showed that ATH-1 could significantly reduce the level of oxidative stress in hypertrophic cardiomyocytes and inhibiting the activation of CaMKII and ERK1/2.},
}

@article {pmid37562904,
year = {2023},
author = {Sukumaran, D and Usharani, P and Paramjyothi, GK and Subbalaxmi, MVS and Sireesha, K and Abid Ali, M},
title = {A study to evaluate the hepatoprotective effect of N- acetylcysteine on anti tuberculosis drug induced hepatotoxicity and quality of life.},
journal = {The Indian journal of tuberculosis},
volume = {70},
number = {3},
pages = {303-310},
doi = {10.1016/j.ijtb.2022.05.012},
pmid = {37562904},
issn = {0019-5707},
mesh = {Humans ; Acetylcysteine/therapeutic use/pharmacology ; Quality of Life ; Prospective Studies ; *Tuberculosis/drug therapy ; *Chemical and Drug Induced Liver Injury/etiology/prevention & control ; Bilirubin ; Biomarkers ; },
abstract = {BACKGROUND: Drug induced liver injury (DILI) is a serious adverse effect caused by first-line anti-TB (ATT) drugs, limiting the TB-treatment. The tissue inflammation induced by free radical burst and poor dietary intake in TB induces oxidative stress, which was proposed as one of the mechanisms responsible for ATT induced DILI. N-acetylcysteine (NAC) exerts a hepato-protective effect by enhancing the cellular antioxidant defense mechanism. There are few studies evaluating the effect of NAC on ATT induced DILI in Indian-population.

METHODS: This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study. Thirty-eight newly diagnosed TB patients on first-line ATT with normal liver function test (LFT) were recruited and randomized to receive either NAC 600 mg tablet or placebo twice daily for 4 weeks and followed-up for next 4 weeks. LFT [AST, ALT, ALP and Total bilirubin] was assessed at baseline, 2, 4 and 8 weeks. Oxidative-stress biomarkers [Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH)] and quality of life (QOL) by SF-36 questionnaire were assessed at baseline, 4 and 8 weeks. Adverse Drug Reactions (ADRs) were monitored at every visit. Compliance was assessed by pill-count method.

RESULTS: Baseline characteristics were homogenous among both the groups. In the NAC group, there was significant reduction in ALT (p < 0.01), ALP (p < 0.01), total bilirubin (p < 0.001) at 4 weeks compared to baseline. AST, MDA and NO showed a reduction of 19%, 21.6% and 5.5% respectively from baseline and GSH at showed an increase of 2.6% from baseline at 4 weeks in the NAC group, however these were not statistically significant. These effects in LFT and oxidative biomarkers persisted even at the end of 8 weeks. Significant improvement from baseline in QOL was observed in both the groups (p < 0.05). Between group analysis showed, significant reduction in ALT (p < 0.05) and AST (p < 0.05) in NAC group at 4 weeks, whereas bilirubin, MDA, NO and GSH showed improvement at 4 weeks compared to placebo in NAC group, however it was not statistically significant. This improvement in the LFT and oxidative biomarkers continued even at the end of 8 weeks. Itching and rashes were the most common ADRs, with similar incidence in both the groups. Compliance to treatment was good in both the groups.

CONCLUSION: Significant improvement in liver function parameters is suggestive of hepatoprotective effect of NAC. This observed effect at 4 weeks was found to be persistent at 8 weeks, which signifies prolonged hepato-protective effect of NAC. Long duration studies with large sample size are required for further confirmation of hepato-protective action of NAC.},
}

Humans
Acetylcysteine/therapeutic use/pharmacology
Quality of Life
Prospective Studies
*Tuberculosis/drug therapy
*Chemical and Drug Induced Liver Injury/etiology/prevention & control
Bilirubin
Biomarkers

@article {pmid37562091,
year = {2023},
author = {Geng, Y and Liu, P and Xie, Y and Liu, Y and Zhang, X and Hou, X and Zhang, L},
title = {Xanthatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {119},
number = {},
pages = {155004},
doi = {10.1016/j.phymed.2023.155004},
pmid = {37562091},
issn = {1618-095X},
mesh = {Humans ; Mice ; Animals ; Reactive Oxygen Species/metabolism ; Mice, Nude ; Cell Line, Tumor ; *Signal Transduction ; Cell Proliferation ; Apoptosis ; Cell Transformation, Neoplastic ; *Pancreatic Neoplasms/drug therapy ; },
abstract = {BACKGROUND: As a malignant digestive system tumor, pancreatic cancer has a high mortality rate. Xanthatin is a sesquiterpene lactone monomer compound purified from the traditional Chinese herb Xanthium strumarium L. It has been reported that Xanthatin exhibits inhibitory effects on various cancer cells in retinoblastoma, glioma, hepatoma, colon cancer, lung cancer, as well as breast cancer. However, in pancreatic cancer cells, only one report exists on the suppression of Prostaglandin E2 synthesis and the induction of caspase 3/7 activation in Xanthatin-treated MIA PaCa-2 cells, while systematic in vitro and in vivo investigations and related mechanisms have yet to be explored.

PURPOSE: This research aims to explore the in vitro and in vivo effects of Xanthatin on pancreatic cancer and its molecular mechanisms.

METHODS: The anticancer effects and mechanisms of Xanthatin on pancreatic cancer cells were assessed through employing cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, carboxyfluorescein diacetate succinimidyl ester (CFDA SE) cell proliferation assay, colony formation assay, wound healing assay, transwell assay, Annexin V-FITC/propidium iodide (PI) dual staining, Hoechst nuclear staining, Western blot analysis, phosphoproteomics, and reactive oxygen species (ROS) measurement. The in vivo anticancer effects of Xanthatin on pancreatic cancer cells were studied using a nude mouse model.

RESULTS: The present study showed that Xanthatin can prevent the proliferation and metastasis of pancreatic cancer cells and trigger the exposure of phosphatidylserine (PS), chromatin condensation, and caspase activation, thereby inducing apoptosis. Phosphoproteomic analysis indicated that Xanthatin inhibits the phosphorylation of the proliferation-associated protein RBL1, and oxidative stress can lead to RBL1 dephosphorylation. Further investigation revealed that Xanthatin significantly upregulates ROS levels in pancreatic cancer cells, and the antioxidant N-acetylcysteine (NAC) can reverse Xanthatin-induced cell proliferation inhibition and apoptosis. In addition, Xanthatin can suppress pancreatic cancer cell growth in a xenograft nude mouse model with low toxicity to the mice.

CONCLUSION: Xanthatin may inhibit the proliferation of pancreatic cancer cells and trigger apoptosis through the ROS/RBL1 signaling pathway.},
}

Humans
Mice
Animals
Reactive Oxygen Species/metabolism
Mice, Nude
Cell Line, Tumor
*Signal Transduction
Cell Proliferation
Apoptosis
Cell Transformation, Neoplastic
*Pancreatic Neoplasms/drug therapy

@article {pmid37561633,
year = {2023},
author = {Yao, H and Chen, X and Wang, T and Kashif, M and Qiao, X and Tüksammel, E and Larsson, LG and Okret, S and Sayin, VI and Qian, H and Bergo, MO},
title = {A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis.},
journal = {Cell reports},
volume = {42},
number = {8},
pages = {112961},
doi = {10.1016/j.celrep.2023.112961},
pmid = {37561633},
issn = {2211-1247},
abstract = {Refractory and relapsed B cell lymphomas are often driven by the difficult-to-target oncogene MYC. Here, we report that high MYC expression stimulates proliferation and protects B lymphoma cells from apoptosis under normal oxidative stress levels and that compounds including N-acetylcysteine (NAC) and vitamin C (VitC) induce apoptosis by reducing oxidative stress. NAC and VitC injections effectively reduce tumor growth in lymphoma cells with high MYC expression but not in those with low MYC expression. MYC knockdown confers tumor resistance to NAC and VitC, while MYC activation renders B cells sensitive to these compounds. Mechanistically, NAC and VitC stimulate MYC binding to EGR1 through Cys117 of MYC, shifting its transcriptional output from cell cycle to apoptosis gene expression. These results identify a redox-controlled mechanism for MYC's role in maintaining proliferation and preventing apoptosis, offering a potential therapeutic rationale for evaluating NAC or VitC in patients with MYC-driven B cell lymphoma.},
}

@article {pmid37559860,
year = {2023},
author = {Mitchell, MC and Rogers, C},
title = {A Case of Cocaine-Induced Acute Liver Failure Reversed With N-Acetylcysteine.},
journal = {Cureus},
volume = {15},
number = {7},
pages = {e41579},
pmid = {37559860},
issn = {2168-8184},
abstract = {Acute liver failure (ALF) is a life-threatening injury that is most often caused by drug-induced injury, including acetaminophen overdose, in the United States. The hallmarks of ALF are hepatic encephalopathy and coagulopathy in a patient without an established history of liver disease. While acetaminophen overdose has an antidote, that is N-acetylcysteine (NAC), when given acutely, most other causes of hepatic failure require an urgent liver transplant. In this paper, we report a case of cocaine-induced acute liver failure that was reversed with the administration of NAC. Our case began when a middle-aged male presented to the emergency department complaining of nausea, vomiting, fatigue, and confusion for the past three days. His past medical history was pertinent for a history of opioid use disorder and his physical exam was remarkable for somnolence, asterixis, and periumbilical ecchymoses. His initial lab results showed markedly elevated liver function tests, prolonged coagulation studies, and a urine drug screen that was positive for cocaine. During the patient's interview, his vital signs became unstable. He was intubated for airway protection and transferred to a tertiary care facility for liver transplant evaluation with the diagnosis of cocaine-induced acute liver failure. There he received NAC, lactulose, rifaximin, and vasopressors. On day two of treatment, his clinical condition greatly improved, and he was extubated. He continued to receive NAC until day five when his liver function tests and coagulopathy improved enough to stop treatment. This case report highlights the clinical benefit of NAC in a case of cocaine-induced acute liver failure, improving the patient's survival and eliminating his need for a liver transplant.},
}

@article {pmid37558010,
year = {2023},
author = {Zhong, G and Guo, Y and Gong, X and Xu, M and Wang, Q and Wu, M and Zhang, X and Liang, Y and Zhao, W and Wang, H and Ye, J},
title = {Enhanced glycolysis by ATPIF1 gene inactivation increased the anti-bacterial activities of neutrophils through induction of ROS and lactic acid.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1869},
number = {8},
pages = {166820},
doi = {10.1016/j.bbadis.2023.166820},
pmid = {37558010},
issn = {1879-260X},
mesh = {Humans ; *Neutrophils/metabolism ; Reactive Oxygen Species/metabolism ; Escherichia coli/metabolism ; *Peritonitis ; Glycolysis ; Nitric Oxide Synthase/metabolism ; Gene Silencing ; Adenosine Triphosphate/metabolism ; },
abstract = {ATP synthase inhibitory factor 1 (ATPIF1) is a mitochondrial protein that regulates the activity of FoF1-ATP synthase. Mice lacking ATPIF1 throughout their bodies (Atpif1[-/-]) exhibit a reduction in the number of neutrophils. However, it remains unclear whether the inactivation of ATPIF1 impairs the antibacterial function of mice, this study aimed to evaluate it using a mouse peritonitis model. Mice were intraperitoneally injected with E. coli to induce peritonitis, and after 24 h, the colonies of E. coli were counted in agarose plates containing mice peritoneal lavage fluids (PLF) or extract from the liver. Neutrophils were analyzed for glucose metabolism in glycolysis following LPS stimulation. Reactive oxygen species (ROS) and lactic acid (LA) levels in neutrophils were measured using flow cytometry and Seahorse analysis, respectively. N-Acetylcysteine (NAC) and 2-Deoxy-d-glucose (2-DG) were employed to assess the role of ROS and LA in neutrophil bactericidal activity. RNA-seq analysis was conducted in neutrophils to investigate potential mechanisms. In ATPIF1[-/-] neutrophils, bactericidal activity was enhanced, accompanied by increased levels of ROS and LA compared to wildtype neutrophils. The augmented bactericidal activity of ATPIF1[-/-] neutrophils was reversed by pretreatment with NAC or 2-DG. RNA-seq analysis revealed downregulation of multiple genes involved in glutathione metabolism, pyruvate oxidation, and heme synthesis, along with increased expression of inflammatory and apoptotic genes. This study suggests that the inactivation of the Atpif1 gene enhances glucose metabolism in neutrophils, resulting in increased bactericidal activity mediated by elevated levels of ROS and LA. Inhibiting ATPIF1 may be a potential approach to enhance antibacterial immunity.},
}

Humans
*Neutrophils/metabolism
Reactive Oxygen Species/metabolism
Escherichia coli/metabolism
*Peritonitis
Glycolysis
Nitric Oxide Synthase/metabolism
Gene Silencing
Adenosine Triphosphate/metabolism

@article {pmid37556466,
year = {2023},
author = {Yu, H and Lv, M and Zhang, S and Zou, K and Qian, Y and Lv, S},
title = {Combination therapy with budesonide and acetylcysteine alleviates LPS-induced acute lung injury via the miR-381/NLRP3 molecular axis.},
journal = {PloS one},
volume = {18},
number = {8},
pages = {e0289818},
pmid = {37556466},
issn = {1932-6203},
mesh = {Animals ; Rats ; *Acetylcysteine/therapeutic use ; *Acute Lung Injury/chemically induced/drug therapy/metabolism ; *Budesonide/therapeutic use ; Lipopolysaccharides/adverse effects ; Lung/pathology ; *MicroRNAs/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; *Pulmonary Edema/pathology ; Signal Transduction ; },
abstract = {BACKGROUND: Acute lung injury (ALI) usually has a high morbidity and mortality rate, but the current treatment is relatively scarce. Both budesonide (Bud) and N-acetylcysteine (NAC) exhibit protective effects in ALI, so we further investigated whether they have a synergistic effect on ALI when used together.

METHODS: Establishment of a rat model of ALI with Lipopolysaccharide (LPS). Bud and NAC were administered by nebulized inhalation alone or in combination. Subsequently, HE staining was performed to observe the pathological changes in lungs of rat. Evans blue staining was implemented to assess alveolar permeability, and the pulmonary edema was assessed by measuring the ratio of wet to dry weight of the lung. Moreover, a TUNEL kit was served to test apoptosis in lung tissues. Western blot and immunohistochemistry were analyzed for expression of scorch-related proteins and NLRP3 in lung tissue, respectively. ELISA was implemented to detect inflammatory factor levels in BALF. and RT-qPCR was utilized to assess the expression level of miR-381. After stable transfection of miR-381 inhibitor or OE-NLRP3 in BEAS-2B treated with LPS, Bud and NAC, miR-381 expression was assessed by RT-qPCR, scorch death-related protein expression was measured by western blot, cell proliferation/viability was assayed by CCK-8, apoptosis was measured by flow cytometry, and ELISA was implemented to assess inflammatory factor levels. Furthermore, the Dual-luciferase assay was used to verify the targeting relationship.

RESULTS: Bud and NAC treatment alone or in combination with nebulized inhalation attenuated the increased alveolar permeability, pulmonary edema, inflammatory response and scorching in LPS-induced ALI rats, and combined treatment with Bud and NAC was the most effective. In addition, combined treatment with Bud and NAC upregulated miR-381 expression and inhibited NLRP3 expression in cellular models and LPS-induced ALI rats. Transfection of the miR-381 inhibitor and OE-NLRP3 partially reversed the protective effects of Bud and NAC combination treatment on BEAS-2B cell proliferation inhibition, apoptosis, focal death and the inflammatory response.

CONCLUSION: Combined Bud and NAC nebulization therapy alleviates LPS-induced ALI by modulating the miR-381/NLRP3 molecular axis.},
}

Animals
Rats
*Acetylcysteine/therapeutic use
*Acute Lung Injury/chemically induced/drug therapy/metabolism
*Budesonide/therapeutic use
Lipopolysaccharides/adverse effects
Lung/pathology
*MicroRNAs/metabolism
NLR Family, Pyrin Domain-Containing 3 Protein/genetics
*Pulmonary Edema/pathology
Signal Transduction

@article {pmid37555614,
year = {2023},
author = {Stannard, L and Doherty, A and Chapman, K and Doak, S and Jenkins, G},
title = {Multi-endpoint analysis of Cadmium Chloride induced genotoxicity shows role for reactive oxygen species and p53 activation in DNA damage induction, cell cycle irregularities and cell size aberrations.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/gead025},
pmid = {37555614},
issn = {1464-3804},
abstract = {Cadmium chloride (CdCl2) is a known genotoxic carcinogen, with a mechanism of action thought to partly involve the generation of reactive oxygen species (ROS). We applied here a multi-endpoint approach in vitro to explore the impact of CdCl2 on both the genome and on wider cell biology pathways relevant to cancer. Multi-endpoint approaches are believed to offer greater promise in terms of understanding the holistic effects of carcinogens in vitro. This richer understanding may help better classification of carcinogens as well as allowing detailed mechanisms of action to be identified. We found that CdCl2 caused DNA damage (micronuclei; MN) in both TK6 and NH32 cells in a dose dependent manner after 4 hours exposure (plus 23 hours recovery), with lowest observable effect levels (LOELs) for MN induction of 1μM (TK6) and 1.6μM (NH32). This DNA damage induction in TK6 cells was ROS dependent as pre-treatment with the antioxidant N Acetyl Cysteine (1mM), abrogated this effect. However, DCFDA was not capable of detecting the ROS induced by CdCl2. The use of NH32 cells allowed an investigation of the role of p53 as they are a p53 null cell line derived from TK6. NH32 showed a 10-fold increase in MN in untreated cells and a similar dose dependent effect after CdCl2 treatment. In TK6 cells, CdCl2 also caused activation of p53 (accumulation of total and phosphorylated p53), imposition of cell cycle checkpoints (G2/M) and intriguingly the production of smaller and more eccentric (elongated) cells. Overall, this multi-endpoint study suggests a carcinogenic mechanism of CdCl2 involving ROS generation, oxidative DNA damage and p53 activation, leading to cell cycle abnormalities and impacts of cell size and shape. This study shows how the integration of multiple cell biology endpoints studied in parallel in vitro can help mechanistic understanding of how carcinogens disrupt normal cell biology.},
}

@article {pmid37554797,
year = {2023},
author = {Zhou, Q and Zhou, Q and Xia, R and Zhang, P and Xie, Y and Yang, Z and Khan, A and Zhou, Z and Tan, W and Liu, L},
title = {Swertiamarin or heat-transformed products alleviated APAP-induced hepatotoxicity via modulation of apoptotic and Nrf-2/NF-κB pathways.},
journal = {Heliyon},
volume = {9},
number = {8},
pages = {e18746},
pmid = {37554797},
issn = {2405-8440},
abstract = {OBJECTIVE: Swertiamarin (STM) belongs to iridoid class of compounds, and the heat-transformed products (HTPS) are produced by STM in the process of drug processing. The purpose of this study was to explore the protective effect and mechanism of STM or HTPS on acetaminophen (APAP)-induced hepatotoxicity.

METHODS: Mice and L-O2 cells were given APAP to establish the hepatotoxicity model in vivo and in vitro. The effects of STM or HTPS on oxidative stress, inflammation, and apoptosis induced by APAP were evaluated, with N-acetylcysteine (NAC) as a positive control.

RESULTS: STM or HTPS reduced the APAP-induced apoptosis of L-O2 cells and significantly alleviated the liver injury index induced by APAP (p < 0.01, 0.005) Interestingly, HTPS had better protective effect against APAP-induced hepatotoxicity than STM (p < 0.05). In addition STM or HTPS improved the histological abnormalities; inhibited lipid peroxidation and reduced the level of inflammatory mediators. They also activated the defense system of nuclear factor erythroid 2 related factor 2 (Nrf-2) and inhibited nuclear factor-κ B (NF-κB).},
}

@article {pmid37547958,
year = {2023},
author = {Wang, X and Liu, B and Liu, Y and Wang, Y and Wang, Z and Song, Y and Xu, J and Xue, C},
title = {Antioxidants ameliorate oxidative stress in alcoholic liver injury by modulating lipid metabolism and phospholipid homeostasis.},
journal = {Lipids},
volume = {58},
number = {5},
pages = {229-240},
doi = {10.1002/lipd.12377},
pmid = {37547958},
issn = {1558-9307},
support = {202012018//Ministry of Education of the People's Republic of China/ ; 2018YFD0901101//Ministry of Science and Technology of the People's Republic of China/ ; },
mesh = {Mice ; Animals ; *Antioxidants/pharmacology/metabolism ; Lipid Metabolism ; Mice, Inbred C57BL ; Liver/metabolism ; Oxidative Stress ; *Liver Diseases, Alcoholic/drug therapy/metabolism ; Ethanol/metabolism/pharmacology ; Ascorbic Acid/metabolism/pharmacology ; Triglycerides/metabolism ; Homeostasis ; Phospholipids/metabolism ; },
abstract = {Alcoholic liver disease (ALD) is a significant risk factor in the global disease burden. The antioxidants vitamin C (Vc) and N-acetyl cysteine (NAC) have shown hepatoprotective effects in preventing and treating ALD. However, the correlation between the improved effect of antioxidants and lipid metabolism is still unclear. In this study, AML12 cells and C57BL/6 mice stimulated with alcohol were used to investigate the protective effects and potential mechanisms of two antioxidants (Vc and NAC) on alcoholic liver injury. Results showed that Vc and NAC attenuated intracellular lipid accumulation and oxidative damage induced by excessive alcohol exposure in hepatic AML12 cells. The in vivo results indicated that antioxidants ameliorated alcohol-induced changes in histopathology, reducing the levels of alcohol metabolizing factors and aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) contents, which demonstrated that antioxidants effectively mitigated liver injury in ALD mice. Further studies showed that antioxidants reversed the disruption of fatty acid (FA) synthesis and lipid transport induced by alcohol exposure, and restored phospholipid levels. Especially, Vc and NAC increased the endogenous antioxidant plasmenyl phosphatidylethanolamine (PlsEtn). Additionally, antioxidants ameliorated the alcohol-impaired mitochondrial function and inhibited excessive oxidative stress. In conclusion, antioxidants can regulate lipid metabolism and phospholipid homeostasis, which in turn inhibit oxidative stress and thereby exert protective effects against ALD.},
}

Mice
Animals
*Antioxidants/pharmacology/metabolism
Lipid Metabolism
Mice, Inbred C57BL
Liver/metabolism
Oxidative Stress
*Liver Diseases, Alcoholic/drug therapy/metabolism
Ethanol/metabolism/pharmacology
Ascorbic Acid/metabolism/pharmacology
Triglycerides/metabolism
Homeostasis
Phospholipids/metabolism

@article {pmid37547194,
year = {2023},
author = {Summerlin, JA and Wang, KM and McMahon, AJ and Lund, JA},
title = {Effect of a pharmacist-based toxicology consult service on appropriate use of intravenous N-acetylcysteine for acetaminophen toxicity: A retrospective cohort study.},
journal = {International journal of critical illness and injury science},
volume = {13},
number = {2},
pages = {54-59},
pmid = {37547194},
issn = {2229-5151},
abstract = {BACKGROUND: Incorporating clinical pharmacists on the medical team has been associated with fewer medication errors and increased error interception. Due to the logistical complexities of the intravenous (IV) N-acetylcysteine (NAC) regimen for acetaminophen toxicity, many opportunities for medication errors exist. A pharmacist-based toxicology consultation service was implemented at our institution, allowing pharmacists to formally aid in the management of toxicology patients throughout their hospital admission, including those with acetaminophen toxicity. The purpose of this study was to evaluate the effect of a house-wide pharmacist-based toxicology consult service on errors associated with IV NAC treatment for patients admitted with acetaminophen toxicity.

METHODS: A retrospective, pre-post cohort study was conducted on patients who received IV NAC for acetaminophen toxicity. The intervention evaluated was the implementation of a pharmacist-based toxicology consult service, known as the pharmacy toxicology team. The primary end point was the incidence of an error associated with IV NAC. An error was defined as the composite of inappropriate dose, administration rate, initiation, continuation, or discontinuation.

RESULTS: Eighty-four patients were included; 30 patients in the pregroup, and 54 patients in the postgroup. Fewer patients experienced an error in the postgroup compared to the pregroup (30% vs 63%, P = 0.003).

CONCLUSION: The implementation of this unique pharmacist-based toxicology consult service was associated with fewer patients experiencing an error related to IV NAC therapy for acetaminophen toxicity. Application of this data may aid in the justification for development of clinical pharmacist-based toxicology consult services at other institutions.},
}

@article {pmid37545886,
year = {2023},
author = {Pimentel, BNADS and De Annunzio, SR and Assis, M and Barbugli, PA and Longo, E and Vergani, CE},
title = {Biocompatibility and inflammatory response of silver tungstate, silver molybdate, and silver vanadate microcrystals.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {11},
number = {},
pages = {1215438},
pmid = {37545886},
issn = {2296-4185},
abstract = {Silver tungstate (α-Ag2WO4), silver molybdate (β-Ag2MoO4), and silver vanadate (α-AgVO3) microcrystals have shown interesting antimicrobial properties. However, their biocompatibility is not yet fully understood. Cytotoxicity and the inflammatory response of silver-containing microcrystals were analyzed in THP-1 and THP-1 differentiated as macrophage-like cells, with the alamarBlue™ assay, flow cytometry, confocal microscopy, and ELISA. The present investigation also evaluated redox signaling and the production of cytokines (TNFα, IL-1β, IL-6, and IL-8) and matrix metalloproteinases (MMP-8 and -9). The results showed that α-AgVO3 (3.9 μg/mL) did not affect cell viability (p > 0.05). α-Ag2WO4 (7.81 μg/mL), β-Ag2MoO4 (15.62 μg/mL), and α-AgVO3 (15.62 μg/mL) slightly decreased cell viability (p ≤ 0.003). All silver-containing microcrystals induced the production of O2 [-] and this effect was mitigated by Reactive Oxygen Species (ROS) scavenger and N-acetylcysteine (NAC). TNFα, IL-6 and IL-1β were not detected in THP-1 cells, while their production was either lower (p ≤ 0.0321) or similar to the control group (p ≥ 0.1048) for macrophage-like cells. The production of IL-8 by both cellular phenotypes was similar to the control group (p ≥ 0.3570). The release of MMP-8 was not detected in any condition in THP-1 cells. Although MMP-9 was released by THP-1 cells exposed to α-AgVO3 (3.9 μg/mL), no significant difference was found with control (p = 0.7). Regarding macrophage-like cells, the release of MMP-8 and -9 decreased in the presence of all microcrystals (p ≤ 0.010). Overall, the present work shows a promising biocompatibility profile of, α-Ag2WO4, β-Ag2MoO4, and α-AgVO3 microcrystals.},
}

@article {pmid37545163,
year = {2023},
author = {Nayak, J and P, SV and Sahoo, SK and Kumar, M and Vashistha, VK and Kumar, R},
title = {Computational insight of antioxidant and doxorubicin combination for effective cancer therapy.},
journal = {Journal of biomolecular structure & dynamics},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/07391102.2023.2242507},
pmid = {37545163},
issn = {1538-0254},
abstract = {Doxorubicin (DOX) is the most effective antineoplastic agent, destroys cancer cells by interrupting cellular function. However, the serious side effects on the heart limits its utility. To curb these unwanted side effects, nutritionist recommend antioxidants use along with DOX while chemotherapy. But it was not supported by various oncologists as it can alter the toxicity of DOX towards cancer cells. Therefore, here we explored the in silico pharmacokinetics and combination effect of DOX and antioxidants on topoisomerases-II (Top-II) and cyclophilin D (Cyp-D) therapeutic targets involved in cancer proliferation and post-myocardial infarction, respectively. The molecular docking study was conducted on target proteins and DOX including most prescribed antioxidants (melatonin, N-acetylcysteine (NAC), glutathione (GSH), β-carotene and vitamin C). GSH showed effective binding potential for Top-II and Cyp-D active sites, but other considered antioxidants possess low binding affinity. The highest docked conformations were subjected to molecular dynamics (MD) simulations to understand conformer stability of DOX and GSH with Cyp-D and Top-II for 100 ns. The results revealed that ligands pose at Top-II active sites where DOX showed strong binding affinity to DNA binding pocket and GSH to a buried site. The computational data summarised and proposed the GSH and DOX combination as antagonist effects on Top-II. Conversely, the binding compactness of GSH improved due to surface fit at the active pocket of Cyp-D and completely blocking DOX binding affinity, suppress adverse reactions of post-myocardial infarction.Communicated by Ramaswamy H. Sarma.},
}

@article {pmid37544576,
year = {2023},
author = {Su, AL and Lash, LH and Loch-Caruso, R},
title = {N-Acetyl-L-cysteine and aminooxyacetic acid differentially modulate toxicity of the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine in human placental villous trophoblast BeWo cells.},
journal = {Toxicology},
volume = {495},
number = {},
pages = {153611},
doi = {10.1016/j.tox.2023.153611},
pmid = {37544576},
issn = {1879-3185},
support = {T32 ES007062/ES/NIEHS NIH HHS/United States ; P42 ES017198/ES/NIEHS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; T32 HD079342/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; Female ; Pregnancy ; *Acetylcysteine/pharmacology/metabolism ; Cysteine ; *Trichloroethylene/toxicity/metabolism ; Placenta/metabolism ; Aminooxyacetic Acid/metabolism/pharmacology ; Trophoblasts/metabolism ; Cytochrome P-450 CYP3A/metabolism ; Hydrogen Peroxide/metabolism ; RNA, Messenger/metabolism ; },
abstract = {Trichloroethylene (TCE) is a known human carcinogen with toxicity attributed to its metabolism. S-(1,2-Dichlorovinyl)-L-cysteine (DCVC) is a metabolite of TCE formed downstream in TCE glutathione (GSH) conjugation and is upstream of several toxic metabolites. Despite knowledge that DCVC stimulates reactive oxygen species (ROS) generation and apoptosis in placental cells, the extent to which these outcomes are attributable to DCVC metabolism is unknown. The current study used N-acetyl-L-cysteine (NAC) at 5 mM and aminooxyacetic acid (AOAA) at 1 mM as pharmacological modifiers of DCVC metabolism to investigate DCVC toxicity at concentrations of 5-50 µM in the human placental trophoblast BeWo cell model capable of forskolin-stimulated syncytialization. Exposures of unsyncytialized BeWo cells, BeWo cells undergoing syncytialization, and syncytialized BeWo cells were studied. NAC pre/co-treatment with DCVC either failed to inhibit or exacerbated DCVC-induced H2O2 abundance, PRDX2 mRNA expression, and BCL2 mRNA expression. Although NAC increased mRNA expression of CYP3A4, which would be consistent with increased generation of the toxic metabolite N-acetyl-DCVC sulfoxide (NAcDCVCS), a CYP3A4 inhibitor ketoconazole did not significantly alter BeWo cell responses. Moreover, AOAA failed to inhibit cysteine conjugate β-lyase (CCBL), which bioactivates DCVC, and did not affect the percentage of nuclei condensed or fragmented, a measure of apoptosis, in all BeWo cell models. However, syncytialized cells had higher CCBL activity compared to unsyncytialized cells, suggesting that the former may be more sensitive to DCVC toxicity. Together, although neither NAC nor AOAA mitigated DCVC toxicity, differences in CCBL activity and potentially CYP3A4 expression dictated the differential toxicity derived from DCVC.},
}

Humans
Female
Pregnancy
*Acetylcysteine/pharmacology/metabolism
Cysteine
*Trichloroethylene/toxicity/metabolism
Placenta/metabolism
Aminooxyacetic Acid/metabolism/pharmacology
Trophoblasts/metabolism
Cytochrome P-450 CYP3A/metabolism
Hydrogen Peroxide/metabolism
RNA, Messenger/metabolism

@article {pmid37540942,
year = {2023},
author = {Kanaan, RA and Oliver, G and Dharan, A and Sendi, S and Maier, A and Mohebbi, M and Ng, C and Back, SE and Kalivas, P and Berk, M},
title = {A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD.},
journal = {Psychiatry research},
volume = {327},
number = {},
pages = {115398},
doi = {10.1016/j.psychres.2023.115398},
pmid = {37540942},
issn = {1872-7123},
mesh = {Adult ; Humans ; *Acetylcysteine/pharmacology/therapeutic use ; *Stress Disorders, Post-Traumatic/drug therapy ; Double-Blind Method ; Treatment Outcome ; },
abstract = {BACKGROUND: PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD.

METHODS: A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks.

RESULTS: 133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC.

CONCLUSION: This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial.

TRIAL REGISTRATION: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.},
}

Adult
Humans
*Acetylcysteine/pharmacology/therapeutic use
*Stress Disorders, Post-Traumatic/drug therapy
Double-Blind Method
Treatment Outcome

@article {pmid37540386,
year = {2023},
author = {Zhang, J and Sun, J and Zhang, Y and Zhang, M and Liu, X and Yang, L and Yin, Y},
title = {Dehydrocostus lactone inhibits Candida albicans growth and biofilm formation.},
journal = {AMB Express},
volume = {13},
number = {1},
pages = {82},
pmid = {37540386},
issn = {2191-0855},
support = {2019SCZT053//the Special Fund for Medical Professionals of Jilin Province/ ; },
abstract = {Candida albicans infections are threatening public health but there are only several antifungal drugs available. This study was to assess the effects of dehydrocostus lactone (DL) on the Candida albicans growth and biofilms Microdilution assays revealed that DL inhibits a panel of standard Candida species, including C. albicans, as well as 9 C. albicans clinical isolates. The morphological transition of C. albicans in RPMI-1640 medium and the adhesion to polystyrene surfaces can also be decreased by DL treatment, as evidenced by microscopic, metabolic activity and colony forming unit (CFU) counting assays. The XTT assay and microscopy inspection demonstrated that DL can inhibit the biofilms of C. albicans. Confocal microscopy following propidium iodide (PI) staining and DCFH-DA staining after DL treatment revealed that DL can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. N-acetyl-cysteine could mitigate the inhibitory effects of DL on growth, morphological transition and biofilm formation, further confirming that ROS production induced by DL contributes to its antifungal and antibiofilm effects. This study showed that DL demonstrated antifungal and antibiofilm activity against C. albicans. The antifungal mechanisms may involve membrane damage and ROS overproduction. This study shows the potential of DL to fight Candida infections.},
}

@article {pmid37537647,
year = {2023},
author = {Refsnes, M and Skuland, T and Jørgensen, R and Sæter-Grytting, V and Snilsberg, B and Øvrevik, J and Holme, JA and Låg, M},
title = {Role of different mechanisms in pro-inflammatory responses triggered by traffic-derived particulate matter in human bronchiolar epithelial cells.},
journal = {Particle and fibre toxicology},
volume = {20},
number = {1},
pages = {31},
pmid = {37537647},
issn = {1743-8977},
mesh = {Humans ; *Particulate Matter/toxicity ; Reactive Oxygen Species/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Cyclooxygenase 2 ; Cytochrome P-450 CYP1A1/genetics ; Plasminogen Activator Inhibitor 2/metabolism/pharmacology ; Cytokines/metabolism ; Epithelial Cells ; Vehicle Emissions/toxicity ; *Air Pollutants/toxicity/metabolism ; },
abstract = {BACKGROUND: Traffic-derived particles are important contributors to the adverse health effects of ambient particulate matter (PM). In Nordic countries, mineral particles from road pavement and diesel exhaust particles (DEP) are important constituents of traffic-derived PM. In the present study we compared the pro-inflammatory responses of mineral particles and DEP to PM from two road tunnels, and examined the mechanisms involved.

METHODS: The pro-inflammatory potential of 100 µg/mL coarse (PM10-2.5), fine (PM2.5-0.18) and ultrafine PM (PM0.18) sampled in two road tunnels paved with different stone materials was assessed in human bronchial epithelial cells (HBEC3-KT), and compared to DEP and particles derived from the respective stone materials. Release of pro-inflammatory cytokines (CXCL8, IL-1α, IL-1β) was measured by ELISA, while the expression of genes related to inflammation (COX2, CXCL8, IL-1α, IL-1β, TNF-α), redox responses (HO-1) and metabolism (CYP1A1, CYP1B1, PAI-2) was determined by qPCR. The roles of the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) were examined by treatment with the AhR-inhibitor CH223191 and the anti-oxidant N-acetyl cysteine (NAC).

RESULTS: Road tunnel PM caused time-dependent increases in expression of CXCL8, COX2, IL-1α, IL-1β, TNF-α, COX2, PAI-2, CYP1A1, CYP1B1 and HO-1, with fine PM as more potent than coarse PM at early time-points. The stone particle samples and DEP induced lower cytokine release than all size-fractionated PM samples for one tunnel, and versus fine PM for the other tunnel. CH223191 partially reduced release and expression of IL-1α and CXCL8, and expression of COX2, for fine and coarse PM, depending on tunnel, response and time-point. Whereas expression of CYP1A1 was markedly reduced by CH223191, HO-1 expression was not affected. NAC reduced the release and expression of IL-1α and CXCL8, and COX2 expression, but augmented expression of CYP1A1 and HO-1.

CONCLUSIONS: The results indicate that the pro-inflammatory responses of road tunnel PM in HBEC3-KT cells are not attributed to the mineral particles or DEP alone. The pro-inflammatory responses seem to involve AhR-dependent mechanisms, suggesting a role for organic constituents. ROS-mediated mechanisms were also involved, probably through AhR-independent pathways. DEP may be a contributor to the AhR-dependent responses, although other sources may be of importance.},
}

Humans
*Particulate Matter/toxicity
Reactive Oxygen Species/metabolism
Tumor Necrosis Factor-alpha/metabolism
Cyclooxygenase 2
Cytochrome P-450 CYP1A1/genetics
Plasminogen Activator Inhibitor 2/metabolism/pharmacology
Cytokines/metabolism
Epithelial Cells
Vehicle Emissions/toxicity
*Air Pollutants/toxicity/metabolism

@article {pmid37537538,
year = {2023},
author = {Duan, Y and Wu, W and Cui, J and Matsubara, JA and Kazlauskas, A and Ma, G and Li, X and Lei, H},
title = {Ligand-independent activation of platelet-derived growth factor receptor β promotes vitreous-induced contraction of retinal pigment epithelial cells.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {344},
pmid = {37537538},
issn = {1471-2415},
support = {2020004//Health Commission of Shanxi Province/ ; 2022-203//Research Project Supported by Shanxi Scholarship Council of China/ ; 2021RC005//Shanxi Bethune Hospital Foundation/ ; 2022Jx22//Shanxi Bethune Hospital Education and Teaching Reform Foundation/ ; 202103021224345//Natural Science Foundation of Shanxi province/ ; 2021JJ41030//Natural Science Foundation of Hunan Province/ ; 82171085//National Natural Science Foundation of China/ ; 82070989//National Natural Science Foundation of China/ ; 19JCZDJC64000//Natural Science Foundation of Tianjin City/ ; G2022026027L//Introduction plan of high-level foreign experts/ ; },
mesh = {Humans ; *Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism ; Retinal Pigment Epithelium/pathology ; Proto-Oncogene Proteins c-akt ; Ligands ; Reactive Oxygen Species/metabolism ; *Vitreoretinopathy, Proliferative/genetics/metabolism ; Platelet-Derived Growth Factor/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; Cell Movement ; },
abstract = {BACKGROUND: Epiretinal membranes in patients with proliferative vitreoretinopathy (PVR) consist of extracellular matrix and a number of cell types including retinal pigment epithelial (RPE) cells and fibroblasts, whose contraction causes retinal detachment. In RPE cells depletion of platelet-derived growth factor (PDGF) receptor (PDGFR)β suppresses vitreous-induced Akt activation, whereas in fibroblasts Akt activation through indirect activation of PDGFRα by growth factors outside the PDGF family (non-PDGFs) plays an essential role in experimental PVR. Whether non-PDGFs in the vitreous, however, were also able to activate PDGFRβ in RPE cells remained elusive.

METHODS: The CRISPR/Cas9 technology was utilized to edit a genomic PDGFRB locus in RPE cells derived from an epiretinal membrane (RPEM) from a patient with PVR, and a retroviral vector was used to express a truncated PDGFRβ short of a PDGF-binding domain in the RPEM cells lacking PDGFRβ. Western blot was employed to analyze expression of PDGFRβ and α-smooth muscle actin, and signaling events (p-PDGFRβ and p-Akt). Cellular assays (proliferation, migration and contraction) were also applied in this study.

RESULTS: Expression of a truncated PDGFRβ lacking a PDGF-binding domain in the RPEM cells whose PDGFRB gene has been silent using the CRISPR/Cas9 technology restores vitreous-induced Akt activation as well as cell proliferation, epithelial-mesenchymal transition, migration and contraction. In addition, we show that scavenging reactive oxygen species (ROS) with N-acetyl-cysteine and inhibiting Src family kinases (SFKs) with their specific inhibitor SU6656 blunt the vitreous-induced activation of the truncated PDGFRβ and Akt as well as the cellular events related to the PVR pathogenesis. These discoveries suggest that in RPE cells PDGFRβ can be activated indirectly by non-PDGFs in the vitreous via an intracellular pathway of ROS/SFKs to facilitate the development of PVR, thereby providing novel opportunities for PVR therapeutics.

CONCLUSION: The data shown here will improve our understanding of the mechanism by which PDGFRβ can be activated by non-PDGFs in the vitreous via an intracellular route of ROS/SFKs and provide a conceptual foundation for preventing PVR by inhibiting PDGFRβ transactivation (ligand-independent activation).},
}

Humans
*Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism
Retinal Pigment Epithelium/pathology
Proto-Oncogene Proteins c-akt
Ligands
Reactive Oxygen Species/metabolism
*Vitreoretinopathy, Proliferative/genetics/metabolism
Platelet-Derived Growth Factor/metabolism
Epithelial Cells/metabolism
Retinal Pigments/metabolism
Cell Movement

@article {pmid37536438,
year = {2023},
author = {Martis, RM and Grey, AC and Wu, H and Wall, GM and Donaldson, PJ and Lim, JC},
title = {N-Acetylcysteine amide (NACA) and diNACA inhibit H2O2-induced cataract formation ex vivo in pig and rat lenses.},
journal = {Experimental eye research},
volume = {234},
number = {},
pages = {109610},
doi = {10.1016/j.exer.2023.109610},
pmid = {37536438},
issn = {1096-0007},
mesh = {Rats ; Animals ; Swine ; Acetylcysteine/adverse effects ; Hydrogen Peroxide/pharmacology ; Cystine/adverse effects ; Chromatography, Liquid ; Rats, Wistar ; Tandem Mass Spectrometry ; *Lens, Crystalline/metabolism ; *Cataract/chemically induced ; Antioxidants ; Oxidative Stress ; Glutathione/metabolism ; Proteins ; Glutathione Disulfide ; },
abstract = {Oxidative stress plays a central role in cataract formation suggesting that antioxidants might slow cataract progression. The anticataract activity of N-acetylcysteine amide (NACA) and (2 R, 2 R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA) and/or N-acetylcysteine (NAC), were evaluated in porcine and rat lens models. Cataractogenesis via oxidation was induced with H2O2 and/or glucose oxidase (GO). Porcine lenses were incubated in 0.1 mM, 1 mM, or 10 mM NAC, NACA or diNACA for 24 h. Lenses were then transferred to media containing 0.75 mM H2O2 and 4.63U of GO in order to maintain a constant H2O2 level for an additional 8 h. At the end of incubation, lenses were imaged under darkfield microscopy. Separately, rat lenses were extracted from 3-week-old Wistar rats and incubated with either 10 mM NACA or 10 mM diNACA for 24 h prior to treatment with 0.2U GO to generate a steady source of ∼0.6 mM H2O2. Rat lenses were analyzed by LC-MS/MS to quantify changes in cysteine, cystine, glutathione (GSH) or oxidised glutathione (GSSG) levels in the lens epithelium, cortex or core. Pre-treatment with NACA or diNACA followed by oxidation with H2O2 and/or GO to stimulate cataract formation afforded rapid assessment in ex vivo porcine (32 h) and rat (48 h) lens models. Pre-treatment of isolated porcine lenses with 0.1 mM, 1 mM or 10 mM of either NAC, NACA or diNACA followed by H2O2/GO treatment resulted in reduced lens opacity relative to the lenses exposed to H2O2/GO, with NACA and diNACA reducing opacities to a greater extent than NAC. Rat lenses incubated with 10 mM NACA or 10 mM diNACA without exposure to H2O2 showed no signs of opacities. Pre-treatment of rat lenses with 10 mM NACA or 10 mM diNACA, followed by GO cataract induction resulted in reduced opacities compared to control (GO alone). LC-MS/MS analyses revealed that NACA, but not diNACA, increased cysteine, cystine and GSH levels in rat lens epithelium and cortex regions. Taken together, both NACA and diNACA inhibited cataract formation to a greater extent than NAC (all at 1-10 mM) in an ex vivo porcine lens model. Both NACA and diNACA (both at 10 mM) reduced cataract formation in rat lenses. Based on LC-MS/MS analyses, NACA-induced reduction in opacity observed in rat lenses was attributed to enhanced cysteine and GSH levels while the diNACA-induced reduction in opacity induced did not consistently increase cysteine, cystine and GSH levels and, therefore, appears to involve a different antioxidant mechanism. These screening studies warrant further testing of NACA and diNACA as anticataract agents.},
}

Rats
Animals
Swine
Acetylcysteine/adverse effects
Hydrogen Peroxide/pharmacology
Cystine/adverse effects
Chromatography, Liquid
Rats, Wistar
Tandem Mass Spectrometry
*Lens, Crystalline/metabolism
*Cataract/chemically induced
Antioxidants
Oxidative Stress
Glutathione/metabolism
Proteins
Glutathione Disulfide

@article {pmid37536084,
year = {2023},
author = {Takeda, H and Murakami, S and Liu, Z and Sawa, T and Takahashi, M and Izumi, Y and Bamba, T and Sato, H and Akaike, T and Sekine, H and Motohashi, H},
title = {Sulfur metabolic response in macrophage limits excessive inflammatory response by creating a negative feedback loop.},
journal = {Redox biology},
volume = {65},
number = {},
pages = {102834},
pmid = {37536084},
issn = {2213-2317},
mesh = {Mice ; Animals ; *Cystine ; Feedback ; *Lipopolysaccharides ; Macrophages/metabolism ; Acetylcysteine ; Sulfur/metabolism ; Amino Acid Transport System y+/genetics/metabolism ; },
abstract = {The excessive inflammatory response of macrophages plays a vital role in the pathogenesis of various diseases. The dynamic metabolic alterations in macrophages, including amino acid metabolism, are known to orchestrate their inflammatory phenotype. To explore a new metabolic pathway that regulates the inflammatory response, we examined metabolome changes in mouse peritoneal macrophages (PMs) in response to lipopolysaccharide (LPS) and found a coordinated increase of cysteine and its related metabolites, suggesting an enhanced demand for cysteine during the inflammatory response. Because Slc7a11, which encodes a cystine transporter xCT, was remarkably upregulated upon the pro-inflammatory challenge and found to serve as a major channel of cysteine supply, we examined the inflammatory behavior of Slc7a11 knockout PMs (xCT-KO PMs) to clarify an impact of the increased cysteine demand on inflammation. The xCT-KO PMs exhibited a prolonged upregulation of pro-inflammatory genes, which was recapitulated by cystine depletion in the culture media of wild-type PMs, suggesting that cysteine facilitates the resolution of inflammation. Detailed analysis of the sulfur metabolome revealed that supersulfides, such as cysteine persulfide, were increased in PMs in response to LPS, which was abolished in xCT-KO PMs. Supplementation of N-acetylcysteine tetrasulfide (NAC-S2), a supersulfide donor, attenuated the pro-inflammatory gene expression in xCT-KO PMs. Thus, activated macrophages increase cystine uptake via xCT and produce supersulfides, creating a negative feedback loop to limit excessive inflammation. Our study highlights the finely tuned regulation of macrophage inflammatory response by sulfur metabolism.},
}

Mice
Animals
*Cystine
Feedback
*Lipopolysaccharides
Macrophages/metabolism
Acetylcysteine
Sulfur/metabolism
Amino Acid Transport System y+/genetics/metabolism

@article {pmid37534881,
year = {2023},
author = {Ding, W and Fan, JH and Zhong, LR and Wang, NX and Liu, LH and Zhang, HB and Wang, L and Wang, MQ and He, BL and Wei, AY},
title = {N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.},
journal = {Asian journal of andrology},
volume = {},
number = {},
pages = {},
doi = {10.4103/aja202324},
pmid = {37534881},
issn = {1745-7262},
abstract = {Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.},
}

@article {pmid37534078,
year = {2023},
author = {Alam, MS and Hasan, MN and Maowa, Z and Khatun, F and Nazir, KHMNH and Alam, MZ},
title = {N-acetylcysteine reduces severity and mortality in COVID-19 patients: A systematic review and meta-analysis.},
journal = {Journal of advanced veterinary and animal research},
volume = {10},
number = {2},
pages = {157-168},
pmid = {37534078},
issn = {2311-7710},
abstract = {OBJECTIVES: Recent clinical studies suggest that oxidative stress is one of the key players in the pathogenesis of coronavirus disease 2019 (COVID-19), and N-acetylcysteine (NAC), a potent antioxidant, has been shown to improve clinical outcomes in COVID-19 patients. We conducted a systematic review and meta-analysis of the literature published on the therapeutic intervention of NAC on COVID-19 infection.

METHODS: We searched PubMed, Google Scholar, and Science Direct. We identified and screened eight studies with 20,503 participants, including 2,852 in the NAC-treated group and 17,651 in the placebo group, which reported the effect of NAC on COVID-19 infection. A meta-analysis was performed using forest plots under fixed effect estimates based on the standardized mean difference (SMD) and risk ratio (RR).

RESULTS: Pooled analysis showed that NAC was associated with lower mortality in patients with COVID-19 compared with the placebo group [RR, 0.65; (95% CI: 0.56 to 0.75); p < 0.0001]. Similarly, C-reactive protein (CRP) [SMD, -0.32; (95% CI: -56 to -0.09); p = 0.0070] and D-dimer [SMD, -0.35, (95% CI: -0.59 to -0.10; p = 0.0062] levels were significantly decreased, and the oxygenation marker, PaO2/FiO2 ratio, was increased in the NAC-treated group compared with the placebo group [SMD, 0.76; (95% CI: 0.48 to 1.03); p < 0.0001].

CONCLUSION: Although the number of included studies was minimal, this meta-analysis suggests that NAC may have a positive effect on COVID-19 outcomes, specifically, a significant decrease in CRP and D-dimer levels and a significant increase in oxygen saturation, which decreased mortality. We have also presented a comprehensive review of the role and mechanisms of NAC in patients with COVID-19.},
}

@article {pmid37532734,
year = {2023},
author = {Chen, W and Yin, Y and Zhang, Z},
title = {Effects of N-acetylcysteine on CG8005 gene-mediated proliferation and apoptosis of Drosophila S2 embryonic cells.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {12502},
pmid = {37532734},
issn = {2045-2322},
mesh = {Animals ; Male ; *Acetylcysteine/pharmacology ; *Antioxidants/pharmacology ; Apoptosis ; Cell Proliferation ; *Drosophila/embryology ; Reactive Oxygen Species/metabolism ; Signal Transduction ; *Drosophila Proteins/genetics/physiology ; },
abstract = {To investigate the effect of the antioxidant N-acetylcysteine (NAC) on the proliferation and apoptosis in CG8005 gene-interfering Drosophila S2 embryonic cells by scavenging intracellular reactive oxygen species (ROS). The interfering efficiency of CG8005 gene in Drosophila S2 embryonic cells was verified by real-time quantitative PCR (qRT-PCR). Different concentrations of NAC and phosphate buffered saline (PBS) were used to affect the Drosophila S2 embryonic cells. The growth state of Drosophila S2 embryonic cells was observed by light microscope. Two probes dihydroethidium (DHE) and 2,7-dichlorodihydrofluorescein-acetoacetate (DCFH-DA) were used to observe the ROS production in each group after immunofluorescence staining. TUNEL staining and flow cytometry were used to investigate the apoptosis level of Drosophila S2 embryos, and CCK-8 (Cell Counting Kit-8) was used to detect the cell viability of Drosophila S2 embryos. The knockdown efficiency of siCG8005-2 fragment was high and stable, which was verified by interference efficiency (P < 0.05). There was no significant change in the growth of Drosophila S2 embryonic cells after the treatment of NAC as compared to PBS group. Moreover, knockdowning CG8005 gene resulted in an increase in ROS and apoptosis in Drosophila S2 embryonic cells (P < 0.05) and a decrease in proliferation activity (P < 0.05). In addition, the pretreatment of antioxidant NAC could inhibit ROS production in Drosophila S2 embryonic cells (P < 0.05), reduce cell apoptosis (P < 0.05), and improve cell survival (P < 0.05). The CG8005 gene in Drosophila S2 embryonic cells could regulate the proliferation and apoptosis of S2 embryonic cells by disrupting the redox homeostasis, and antioxidant NAC could inhibit cell apoptosis and promotes cell proliferation by scavenging ROS in Drosophila S2 embryonic cells, which is expected to provide novel insights for the pathogenesis of male infertility and spermatogenesis.},
}

Animals
Male
*Acetylcysteine/pharmacology
*Antioxidants/pharmacology
Apoptosis
Cell Proliferation
*Drosophila/embryology
Reactive Oxygen Species/metabolism
Signal Transduction
*Drosophila Proteins/genetics/physiology

@article {pmid37531905,
year = {2023},
author = {Zhai, BW and Zhao, H and Zhu, HL and Huang, H and Zhang, MY and Fu, YJ},
title = {Triterpene acids from Rosa roxburghii Tratt fruits exert anti-hepatocellular carcinoma activity via ROS/JNK signaling pathway-mediated cell cycle arrest and mitochondrial apoptosis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {119},
number = {},
pages = {154960},
doi = {10.1016/j.phymed.2023.154960},
pmid = {37531905},
issn = {1618-095X},
mesh = {Humans ; Reactive Oxygen Species/metabolism ; MAP Kinase Signaling System ; *Rosa ; Fruit ; *Carcinoma, Hepatocellular/pathology ; Cell Cycle Checkpoints ; Apoptosis ; Hep G2 Cells ; *Triterpenes/pharmacology ; *Liver Neoplasms/pathology ; Cell Line, Tumor ; },
abstract = {BACKGROUND: Rosa roxburghii Tratt (RRT) is a famous healthy and medicinal edible fruit in southwest China and has been shown to have some hepatoprotective properties. However, whether the active components, such as the triterpene acids from Rosa roxburghii Tratt fruits (TAR), have anti-hepatocellular carcinoma (HCC) effects and the potential molecular mechanisms are still unclear.

PURPOSE: This study aimed to investigate the anti-HCC effects and potential action mechanisms of triterpene components in RRT fruits.

METHODS: The triterpene acids in TAR were analyzed by using UPLC-Q-Exactive Orbitrap/MS, and the main components were virtual screening for targets based on pharmacophore and then performed enrichment analysis. HepG2 cells were used for in vitro experiments, including MTT assay, wound healing assay, and flow cytometry to detect cell cycle, reactive oxygen species (ROS) level, caspase-3 activity, and mitochondrial membrane potential (MMP) changes. Moreover, the western blot was used to detect mitochondrial apoptosis and ROS/ c-Jun N-terminal kinase (JNK) signaling pathway-related proteins.

RESULTS: The main components in TAR are pentacyclic triterpene acids (mainly euscaphic acid and roxburic acid). TAR could inhibit cell viability, cell migration ability and suppress the proliferation of HepG2 cells through G2/M cell cycle arrest. On the other hand, TAR could induce HepG2 cells apoptosis, which was achieved by causing the accumulation of ROS and activation of the JNK signaling pathway, and our research showed that this apoptosis was mediated through the mitochondrial pathway. In addition, the free radical scavenger N-acetyl cysteine (NAC) could attenuate TAR-induced ROS accumulation and JNK signaling pathway activation, which ultimately reversed mitochondrial apoptosis.

CONCLUSION: TAR could activate the ROS/JNK signaling pathway, which could inhibit the proliferation through G2/M cell cycle arrest and promote apoptosis through the mitochondrial pathway in HCC cells. This supports the anti-tumor potential in RRT fruits.},
}

Humans
Reactive Oxygen Species/metabolism
MAP Kinase Signaling System
*Rosa
Fruit
*Carcinoma, Hepatocellular/pathology
Cell Cycle Checkpoints
Apoptosis
Hep G2 Cells
*Triterpenes/pharmacology
*Liver Neoplasms/pathology
Cell Line, Tumor

@article {pmid37522559,
year = {2023},
author = {Kaur, K and Chen, PC and Ko, MW and Huerta-Yepez, S and Maharaj, D and Jewett, A},
title = {The Potential Role of Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis (ALS); A Longitudinal Case Study Comparing Patients with Genetically Identical Healthy Twin.},
journal = {Critical reviews in immunology},
volume = {43},
number = {1},
pages = {27-39},
doi = {10.1615/CritRevImmunol.2023047233},
pmid = {37522559},
issn = {1040-8401},
abstract = {Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neurons. The causes of ALS are heterogeneous, and are only partially understood to date. We studied percentage and function of immune cell subsets in particular natural killer (NK) and CD8+ T cells in an ALS patient and compared the results to those obtained from his genetically identical healthy twin in a longitudinal study. We found several basic mechanisms which were potentially involved in the disease induction and progression. Our findings demonstrate that ALS patient's peripheral blood contained higher NK and B cells and, lower T cell percentages compared with the healthy twin brother's peripheral blood. Significantly increased interferon-gamma secretion by anti-CD3/28 monoclonal antibody-treated peripheral blood mononuclear cells, and sorted CD8+ T cells were observed in the ALS patient, suggesting that hyper-responsiveness of T cell compartment could be a potential mechanism of ALS progression. Significant increase in NK cell function due to genetic mutations in ALS associated genes may partly be responsible for the increase expansion and function of CD8+ T cells with effector/memory phenotype, in addition to direct activation and expansion of antigen specific T cells by such mutations. Weekly N-acetyl cysteine infusion to block cell death in patient in addition to a number of other therapies listed in this paper were not effective, and even though the treatments might have extended the patient's life, it was not curative. Therefore, activated CD8+ T and NK cells are likely cells targeting motor neurons in the patient, and strategies should be designed to decrease the aggressive nature of these cells to achieve longer lasting therapeutic benefits.},
}