@article {pmid42774381,
year = {2026},
author = {Wan, S and Huang, T and Li, J and Lv, N and Lu, J and Zhang, Y and Zhou, A and Chen, R},
title = {Spread potential and architectural variant of a multiple-drug resistant Escherichia coli co-producing lipopolysaccharide-modifying determinants and extended-spectrum β-lactamases.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1924788},
pmid = {42774381},
issn = {1664-302X},
abstract = {BACKGROUND: Abuse of β-lactam antibiotics and its spread of drug resistance challenged the applicability of antimicrobial agents, enabling polymyxins as a last-line treatment for anti-infections of multi-drug resistant (MDR) pathogen. Polymyxin is applicable to herb breeding/growth prompting and combatting Gram-negative bacteria by combining other antimicrobials by membrane dysfunction, permeability damage, vesicle-vesicle contacts and oxidative stress, with its increasingly ubiquitous resistance. However, the complex mechanisms and high transmission risk of polymyxin resistance pose a severe threat to public health, such as improved colonization advantages and infection risks of Escherichia coli.

METHODS: In this study, a polymyxin-resistant Escherichia coli strain capable of producing extended-spectrum β-lactamase (ESBL), thereafter designated as EcE.ESBL.COL, was isolated from a urine sample. Antimicrobial susceptibility testing and whole-genome sequencing revealed that this strain likely harbors multiple antibiotic resistance determinants.

RESULTS: Therefore, these candidates were found on one chromosome [an integron-like MDR region not detected in another ST1485 representative strain (O83:H42)] and three plasmids (including bla TEM - 1B and bla CTX - M-55) in this strain, pertaining to multi-locus sequence type (MLST) 1485 and serotype O25:H42. Interestingly, this genomic region of plasticity with similar arrangements located on either chromosome or plasmid in other distantly-related strains [for example, the chromosome of E. coli strain LWY24 (previously as ST93, reclassified into ST457 in our study) and plasmid pFXCREC004-1, harbored by E. coli strain FXCREC004 (ST101)]. Next, an arnBCADTEF operon and no mcr-like determinant was found on EcE.ESBL.COL chromosome, facilitating the 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification of lipid A in lipopolysaccharide (LPS). Interestingly, polymyxin resistance conferred by arn was augmented by additional polysaccharides retrieved from Lycium barbarum (LBP) and antioxidant N-acetylcysteine (NAC), while no significant antimicrobial coordination was observed if combined with colistin. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and comparative transcriptomics demonstrated that the LPS production and morphology significantly varied in response to polymyxin stress, indicating that polymyxin can induce the transcription of arnBCADTEF, thereby promoting L-Ara4N modification and polymyxin resistance.

CONCLUSION: Overall, our finding indicates that the co-occurrence of antibiotic resistance factors (such as MDR candidates and LPS architectural variation in this isolate) involves both chromosomal recombination and plasmid dissemination, thereby highlighting important implications for antimicrobial resistance surveillance, molecular epidemiological retrospection, and precision clinical anti-infection.},
}

@article {pmid42776345,
year = {2026},
author = {Ghafari, BM and Rajabi, A and Geramifar, P and Rahimi, A and Moghadam, HK and Rahmani, K and Rahimmi, A},
title = {Randomized, placebo-controlled trial of N-acetylcysteine in Parkinson's disease patients: a pilot study.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42776345},
issn = {1573-7365},
support = {IR.MUK.REC.1397/348//Kurdistan University Of Medical Sciences/ ; },
mesh = {Humans ; *Acetylcysteine/therapeutic use ; Male ; Pilot Projects ; Female ; *Parkinson Disease/drug therapy/diagnostic imaging ; Aged ; Middle Aged ; *Antiparkinson Agents/therapeutic use ; Double-Blind Method ; Treatment Outcome ; Levodopa/therapeutic use ; Tomography, Emission-Computed, Single-Photon ; },
abstract = {This pilot trial evaluated the one-year tolerability of oral N-acetylcysteine (NAC) 1200 mg/day in Parkinson's disease (PD) and explored associations with clinical progression, levodopa dose, and striatal dopamine-transporter imaging. Forty-two patients were randomized to NAC or matching placebo twice daily for 12 months in addition to usual care. Completers (n = 32) were assessed at baseline and 12 months with the original UPDRS parts I-IV, 99mTc-TRODAT-1 SPECT, prescribed levodopa dose, and liver/kidney tests. Analyses included paired t-tests, Welch tests of change scores, and linear mixed-effects models with a group × time interaction adjusted for age, sex, and disease duration. No multiplicity correction was applied; results are exploratory. Thirty-two of 42 randomized patients completed both visits. Total UPDRS increased in both groups, but less with NAC than placebo (mean Δ + 5.4 vs. + 9.5 points; difference - 4.1, 95% CI - 7.6 to - 0.5; p = 0.028; mixed-model group × time p = 0.024). Mood-item change also differed (difference - 0.64, 95% CI - 1.17 to - 0.11; p = 0.020). TRODAT binding declined less with NAC (difference in change + 5.5 units, 95% CI 1.7 to 9.3; p = 0.006; group × time p = 0.004). The ≤ 4-year subgroup comprised 9/17 (53%) NAC and 7/15 (47%) placebo participants and showed a similar pattern. Levodopa-dose change was not significant between groups after ANCOVA adjustment for baseline dose, age, sex, and disease duration (adjusted difference - 86 mg/day, 95% CI - 235 to + 64; p = 0.25). Completer laboratory values were stable; discontinuations were not characterized for adverse events. One-year oral NAC was associated with more favorable exploratory clinical and imaging trajectories than placebo. Completer laboratories were unremarkable, but safety cannot be established from completers alone. These data do not establish disease modification and require confirmation in a larger, prospectively powered trial.},
}

Humans
*Acetylcysteine/therapeutic use
Male
Pilot Projects
Female
*Parkinson Disease/drug therapy/diagnostic imaging
Aged
Middle Aged
*Antiparkinson Agents/therapeutic use
Double-Blind Method
Treatment Outcome
Levodopa/therapeutic use
Tomography, Emission-Computed, Single-Photon

@article {pmid42780769,
year = {2026},
author = {Amiri, M and Cheraghi, M and Khalili, F and D'Ambrosio, L and Centis, R and Dinh-Xuan, AT and Venketaraman, V and Nasiri, MJ and Migliori, GB},
title = {Clinical effects of N-acetylcysteine in ICU patients with respiratory disease: a systematic review and meta-analysis.},
journal = {Respiratory research & clinical practice},
volume = {52},
number = {1},
pages = {e20250438},
pmid = {42780769},
issn = {3086-3910},
support = {R15 HL143545/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Acetylcysteine/therapeutic use ; *Intensive Care Units/trends ; Hospital Mortality/trends ; Length of Stay ; Respiration, Artificial ; Randomized Controlled Trials as Topic/methods ; *Expectorants/therapeutic use ; Critical Illness ; *Respiratory Tract Diseases/drug therapy/mortality ; },
abstract = {OBJECTIVE: Critically ill patients with respiratory disease often experience impaired airway clearance, which contributes to adverse clinical outcomes. N-acetylcysteine (NAC) has mucolytic and antioxidant properties, and may have therapeutic potential in this setting. This study evaluated the impact of NAC on clinical outcomes in ICU patients with underlying respiratory disease.

METHODS: A systematic literature search was conducted in PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from January of 2000 to July of 2025 in order to identify randomized controlled trials evaluating NAC in ICU patients with respiratory conditions. Primary outcomes included hospital mortality, duration of mechanical ventilation, ICU length of stay (LOS), and hospital LOS. Data were synthesized using fixed- or random-effects models based on heterogeneity. Subgroup analyses were performed based on the route of NAC administration.

RESULTS: Five randomized controlled trials comprising 340 patients were included. Hospital mortality was 44.76% in the NAC group and 47.61% in the control group (OR = 0.87; 95% CI: 0.49-1.53). No significant differences were observed in ventilation duration (mean difference [MD] = 0.79 days; 95% CI: -2.87 to 4.44) or ICU LOS (MD = 0.21 days; 95% CI: -3.75 to 4.17). However, NAC was associated with a shorter hospital stay (MD = -3.84 days; 95% CI: -7.44 to -0.24). Subgroup analysis suggested variability in mortality outcomes based on administration route.

CONCLUSIONS: NAC may reduce hospital LOS in critically ill patients with respiratory disease, although its effects on mortality and ventilation duration remain inconclusive. These findings may inform future research, particularly in patients with post-infectious lung damage such as that seen in COVID-19 or tuberculosis.},
}

Humans
*Acetylcysteine/therapeutic use
*Intensive Care Units/trends
Hospital Mortality/trends
Length of Stay
Respiration, Artificial
Randomized Controlled Trials as Topic/methods
*Expectorants/therapeutic use
Critical Illness
*Respiratory Tract Diseases/drug therapy/mortality

@article {pmid42781143,
year = {2026},
author = {Khorasani, F and Mirabi, P and Esmaeilzadeh, S},
title = {The Effect of N-Acetyl Cysteine on Serum Lipid Profile and Heavy Metals in Women With Endometriosis Undergoing ICSI: A Randomized Controlled Trial.},
journal = {Health science reports},
volume = {9},
number = {10},
pages = {e73026},
pmid = {42781143},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Endometriosis is associated with oxidative stress and heavy metal accumulation. This study evaluated whether N-acetylcysteine (NAC) reduces serum heavy metals and improves lipid profiles in women with endometriosis undergoing fertility treatment.

METHODS: In this randomized controlled trial, 60 women with laparoscopy-confirmed endometriosis were allocated to NAC (1.8-3 g/day, increased to 3 g/day in participants with BMI ≥ 25 kg/m) or control groups for 6 weeks. Serum levels of lead, cadmium, nickel, chromium, and lipid profiles were measured using atomic absorption spectroscopy and enzymatic assays. Primary outcomes were heavy metal changes; secondary outcomes were lipid profile alterations.

RESULTS: Baseline characteristics were comparable between groups. After 6 weeks, NAC significantly reduced serum lead (MD -0.6 μg/dL; Cohen's d = 0.62; p = 0.03) and nickel (MD -0.8 μg/dL; Cohen's d = 0.59; p = 0.04), both with medium effect sizes. Cadmium and chromium changes were not significant. NAC also significantly reduced total cholesterol (MD -28.4 mg/dL; Cohen's d = 2.01; p < 0.001) and triglycerides (MD -19.7 mg/dL; Cohen's d = 1.45; p < 0.001), representing large effects. HDL decreased modestly (MD -5.2 mg/dL; Cohen's d = 0.89; p = 0.001), with no significant change in LDL.

CONCLUSION: NAC supplementation was associated with reduced serum lead and nickel concentrations and improved lipid parameters in women with endometriosis undergoing ICSI. However, the observed reduction in HDL cholesterol warrants cautious interpretation, and further studies are required to confirm these findings and clarify their clinical significance.},
}

@article {pmid42783965,
year = {2026},
author = {Tang, Y and Lian, Y and Li, S and Ling, E and Wei, D and Huang, W},
title = {N-Acetylcysteine Attacks Phenoloxidase to Inhibit Insect Melanization and Boost Fungal Virulence.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {12},
number = {9},
pages = {},
doi = {10.3390/jof12090670},
pmid = {42783965},
issn = {2309-608X},
support = {32372617//National Natural Science Foundation of China/ ; 32070507//National Natural Science Foundation of China/ ; 32070495//National Natural Science Foundation of China/ ; },
abstract = {The prophenoloxidase (PPO) melanization cascade is a cornerstone of insect humoral immunity against fungal pathogens, yet its direct fungicidal mechanism remains undefined, and strategies to safely manipulate this pathway for biological control are lacking. Here, we demonstrate that infection of Drosophila by the entomopathogenic fungus Beauveria bassiana elicits a surge in phenoloxidase (PO) activity directly triggered by the fungal cell wall component β-1,3-Glucan. This activated PO generates reactive oxygen species (ROS) that are essential for restricting fungal proliferation, thereby establishing a mechanistic link between cascade activation and fungicidal outcome. Critically, we uncover that N-acetylcysteine (NAC), a safe, low-cost pharmaceutical in global clinical use, acts as a potent direct inhibitor of PO enzymatic activity, neutralizing the melanization-driven ROS burst. NAC-mediated inhibition significantly accelerates B. bassiana virulence and host mortality in vivo. Our work defines a new molecular function for NAC as a melanization inhibitor and reveals a safe, translatable strategy to suppress host immune defenses, offering a promising approach to enhance the efficacy of fungal biopesticides for sustainable pest control worldwide.},
}

@article {pmid42784428,
year = {2026},
author = {Sachithanandam, SV and Somashekar, N and Dev, A},
title = {Acute Hepatocellular Drug-induced Liver Injury following Cosmetic Liquid Lipo Injection Complicated by Anaphylactic Reaction to N-acetylcysteine.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_878_26},
pmid = {42784428},
issn = {0975-5764},
abstract = {Drug-induced liver injury (DILI) may occur after exposure to prescription medications, supplements, or non-standardized cosmetic preparations. Cosmetic "liquid lipo" injections are increasingly used for localized fat reduction, but systemic hepatic complications are rarely reported. A 31-year-old woman with no prior liver disease presented with nausea, vomiting, jaundice, and generalized pruritus shortly after receiving a cosmetic "liquid lipo" injection containing deoxycholic acid, phosphatidylcholine, and L-carnitine. Initial laboratory evaluation showed severe hepatocellular liver injury with aspartate aminotransferase 1901 U/L, alanine aminotransferase 2227 U/L, alkaline phosphatase 213 U/L, total bilirubin 6.2 mg/dL, and an R ratio of 6.6. Abdominal imaging showed no biliary obstruction or hepatic mass. Viral, HIV, Epstein-Barr virus, cytomegalovirus, and autoimmune workup were unrevealing. Intravenous N-acetylcysteine (NAC) was initiated for suspected severe DILI, but the patient developed an acute anaphylactic reaction requiring discontinuation of the infusion and treatment with epinephrine, diphenhydramine, and methylprednisolone. She remained hemodynamically stable without encephalopathy or progression to acute liver failure. Liver tests improved with supportive management, and biochemical recovery was documented on outpatient follow-up. Cosmetic liquid lipo injection may be associated with severe hepatocellular DILI. Clinicians should obtain a detailed cosmetic procedure exposure history in unexplained acute liver injury and remain alert to hypersensitivity reactions during intravenous NAC therapy.},
}

@article {pmid42784912,
year = {2026},
author = {Ali, F and Wajid, N and Nadeem, MS},
title = {N-acetyl cysteine (NAC) preconditioning enhances the efficacy of bone marrow derived mesenchymal stem cells for healing of skin burn wounds.},
journal = {Injury},
volume = {57},
number = {11},
pages = {113726},
doi = {10.1016/j.injury.2026.113726},
pmid = {42784912},
issn = {1879-0267},
abstract = {Burn injuries are associated with excessive oxidative stress and inflammation that impair mesenchymal stem cell (MSC) survival and regenerative function. This study investigated whether N-acetylcysteine (NAC) preconditioning could enhance the therapeutic efficacy of bone marrow-derived MSCs (BMSCs) in oxidative stress conditions and burn wound healing. In vitro, BMSCs were preconditioned with NAC (5 or 10 mM) prior to H2O2 exposure, and cell viability, proliferation, oxidative stress markers, and regenerative gene and protein expression were evaluated. In vivo, BMSCs isolated from male Sprague Dawley rats were transplanted into second-degree thermal burn wounds induced in female rats, and wound healing was assessed over 21 days using macroscopic, histological, biochemical, and molecular analyses. NAC preconditioning significantly improved BMSC viability, proliferation, and morphology under oxidative stress while reducing LDH release. NAC-treated BMSCs exhibited increased antioxidant enzyme activities (SOD, CAT, and GSH), reduced malondialdehyde (MDA) levels, and enhanced expression of PCNA, SDF-1, CXCR4, VEGF-A, and IGF-1. In vivo, transplantation of NAC-preconditioned BMSCs accelerated wound contraction, improved re-epithelialization, increased hydroxyproline content, and promoted collagen deposition and tissue regeneration. Furthermore, NAC-preconditioned BMSCs enhanced antioxidant defenses and upregulated SDF-1, CXCR4, VEGF-A, and IGF-1 expression in wound tissues. Collectively, these findings demonstrate that NAC preconditioning enhances the survival, antioxidant capacity, paracrine activity, and regenerative potential of BMSCs, resulting in improved burn wound healing. NAC-preconditioned BMSCs may represent a promising strategy for stem cell-based treatment of burn injuries.},
}

@article {pmid42792564,
year = {2026},
author = {Khan, LK and Almutairi, MM and Abdullah, ML and Alali, AS and Alanazi, AK and Alotaibi, MR and As Sobeai, HM and Alotaibi, AF and Alrashedi, FA and AlSharari, SD and Sari, Y and Algahtani, T and Alasmari, F},
title = {N-Acetylcysteine Attenuates Amikacin-Induced Biochemical, Inflammatory, and Histopathological Alterations in Mice.},
journal = {Biology},
volume = {15},
number = {18},
pages = {},
doi = {10.3390/biology15181618},
pmid = {42792564},
issn = {2079-7737},
support = {ORF-2026-235//The Ongoing Resrarch Funding program, (ORF-2026-235), King Saud University, Riyadh, Saudi Arabia/ ; },
abstract = {Background: Amikacin is an effective aminoglycoside antibiotic, but its clinical use is limited by nephrotoxicity, hepatotoxicity, and neurotoxicity. N-acetylcysteine (NAC), a glutathione precursor and antioxidant, may help reduce these side effects. This study evaluated whether NAC attenuated selected amikacin-induced biochemical, inflammatory, and histopathological alterations in mice. Methods: Male Swiss albino mice were divided into four groups: control, amikacin, NAC, and amikacin-NAC, and the behavioral performance was assessed using the light-dark box test. Serum samples were collected for measurements of kidney and liver biomarkers, metabolic markers, and electrolytes (calcium, inorganic phosphate, and uric acid). A multiplex cytokine/chemokine panel was used to assess the effects of amikacin with/without NAC on systemic inflammation. Results: Amikacin-treated mice showed a reduction in the time spent in the light area, and this effect was improved by NAC. Amikacin also altered certain biochemistry parameters, increasing levels of aspartate transferase and albumin; these changes were attenuated by NAC. Amikacin caused marked increases in certain inflammatory cytokines and chemokines, including IL-6, IL-12p70, IL-22, IL-18, CXCL10, and CCL11. Treatment with NAC lowered IL-6, IL-12p70, IL-22, IL-18, CXCL10, and CCL11. The sparse partial least squares discriminant and heatmap analysis of the serum inflammatory profile revealed segregation of the amikacin group from the other three groups. Importantly, the histopathological assays on renal and cerebral cortex showed NAC caused improvements, with well-shaped tissues, attenuating the cortical histopathological alterations observed in animals treated with amikacin. Conclusions: These findings suggest that NAC may have the potential to attenuate certain biochemical, inflammatory, and histopathological alterations associated with high-dose amikacin exposure.},
}

@article {pmid42793131,
year = {2026},
author = {Ayağ, ME and Tuncer, MC and Öztürk, Ş},
title = {Epigallocatechin Gallate Modulates the Cellular Response to Doxorubicin in HeLa Cervical Cancer Cells.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091299},
pmid = {42793131},
issn = {2218-273X},
mesh = {Humans ; *Catechin/analogs & derivatives/pharmacology ; *Doxorubicin/pharmacology ; Female ; HeLa Cells ; *Uterine Cervical Neoplasms/drug therapy/metabolism/pathology ; Apoptosis/drug effects ; Caspase 3/metabolism/genetics ; Cell Survival/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Caspase 7/metabolism/genetics ; ErbB Receptors/metabolism/genetics ; HaCaT Cells ; },
abstract = {Cervical cancer remains a major cause of cancer-related mortality worldwide, highlighting the need for strategies that may improve responses to conventional chemotherapeutics. Epigallocatechin gallate (EGCG), a green-tea polyphenol with diverse biological activities, has been investigated as a potential chemosensitizing agent. This study evaluated the interaction between EGCG and doxorubicin (DOX) in HeLa cervical cancer cells, with HaCaT keratinocytes included as a non-malignant comparator. Cell viability and drug interactions were assessed using the CCK-8 assay and Chou-Talalay combination index (CI) analysis. Complementary assays evaluated membrane integrity, wound closure, apoptosis, cell-cycle distribution, intracellular DCF-associated fluorescence with or without N-acetylcysteine (NAC) pretreatment, caspase-3 immunoreactivity, and EGFR, FOXP3, CASP3, and CASP7 mRNA expression. Network-based analyses were additionally used to identify candidate molecular associations and pathways. CI analysis demonstrated synergistic EGCG-DOX interactions in HeLa cells under the tested conditions, whereas additive or antagonistic interactions predominated in HaCaT cells. Combined treatment produced the greatest reduction in viable cells, increased apoptosis, altered cell-cycle distribution, and reduced wound closure. It also produced the highest viability-normalized DCF-associated fluorescence, which was attenuated by NAC pretreatment, indicating an antioxidant-sensitive change in intracellular oxidative status without establishing a causal role in cytotoxicity. Combined treatment was further associated with increased total caspase-3 immunoreactivity and altered EGFR, FOXP3, CASP3, and CASP7 transcript levels. Overall, EGCG and DOX exhibited synergistic interactions and multiple treatment-associated cellular and transcriptional responses in HeLa cells under the present in vitro conditions. These findings do not establish cancer-specific selectivity or a definitive molecular mechanism but provide a basis for validation in additional cervical cancer models and at clinically relevant exposures.},
}

Humans
*Catechin/analogs & derivatives/pharmacology
*Doxorubicin/pharmacology
Female
HeLa Cells
*Uterine Cervical Neoplasms/drug therapy/metabolism/pathology
Apoptosis/drug effects
Caspase 3/metabolism/genetics
Cell Survival/drug effects
Gene Expression Regulation, Neoplastic/drug effects
Caspase 7/metabolism/genetics
ErbB Receptors/metabolism/genetics
HaCaT Cells

@article {pmid42765310,
year = {2026},
author = {Tuncer, S and Tuncer Peker, T and Dalkılıc, N},
title = {N-acetylcysteine modulates peripheral nerve excitability and conduction in a rat Model of chronic organophosphate exposure.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/01480545.2026.2734923},
pmid = {42765310},
issn = {1525-6014},
abstract = {Chronic low-dose exposure to organophosphate pesticides has been associated with persistent peripheral neurotoxicity, yet the functional mechanisms underlying axonal dysfunction remain insufficiently defined. We investigated the effects of chronic diazinon exposure on peripheral nerve excitability and conduction properties in rats and evaluated the potential protective role of N-acetylcysteine (NAC). Adult male Wistar rats were allocated to four groups (n = 9 each): control (CON), diazinon (COP), combined treatment (COP+NAC), and NAC alone (NAC) for four weeks. Axonal excitability of the caudal nerve was assessed in vivo using threshold tracking, and sciatic nerve compound action potentials were recorded ex vivo with estimation of conduction velocity distributions. Diazinon exposure reduced rheobase and refractoriness, shortened the relative refractory period, increased superexcitability, and decreased the resting I/V slope, consistent with membrane depolarization and altered sodium channel function. Compound action potential amplitude and area were significantly reduced, accompanied by a shift toward slower-conducting fibers, indicating preferential impairment of fast axons. Concurrent NAC treatment partially normalized excitability parameters and attenuated conduction velocity shifts, while NAC alone produced mild hyperpolarizing changes. These findings indicate that chronic diazinon exposure disrupts axonal membrane properties and selectively affects fast-conducting fibers, and that NAC may mitigate these functional alterations.},
}

@article {pmid42767289,
year = {2026},
author = {Haraźna, K and Träger, D and Winiarska, A and Wesołowska, J and Niziołek, K and Słota, D and Lis, K and Sobczak-Kupiec, A},
title = {Enzyme-mediated crosslinking of silk fibroin/ N-acetylcysteine-modified chitosan/hydroxyapatite hydrogel composites for subchondral bone regeneration.},
journal = {International journal of biological macromolecules},
volume = {383},
number = {Pt 1},
pages = {154570},
doi = {10.1016/j.ijbiomac.2026.154570},
pmid = {42767289},
issn = {1879-0003},
abstract = {Composite hydrogels based on N-acetylcysteine-modified chitosan (CHS-NAC), silk fibroin (SF), and hydroxyapatite (HAp) were developed via horseradish peroxidase (HRP)-mediated enzymatic crosslinking for subchondral bone regeneration. The novelty of the system lies in integrating NAC-modified chitosan, characterised by reactive -SH groups and antioxidant activity, with SF and HAp within a single enzymatically crosslinked matrix, while directly comparing synthesised (HAp-syn) and commercial (HAp-com) mineral phases. CHS-NAC contained 225.35 μmol g[-1] -SH groups and exhibited antioxidant activity of 13.91 ± 0.71 μg Trolox equivalents per g[-1]of materials. Although SF reduced antioxidant activity by ∼25%, incorporating either HAp restored it to levels comparable to CHS-NAC. The hydrogels exhibited interconnected porosity, composition-dependent swelling, stability in simulated physiological media, and predominantly elastic behaviour (G' > G″). HAp markedly increased rheological stiffness, with CHS-NAC_SF_5HAp-syn showing the highest G' and the greatest critical strain among HAp-containing composites. HAp-syn also enabled more controlled modulation of surface roughness than HAp-com. Biological evaluation confirmed the absence of sustained cytotoxic effects and progressive MC3T3-E1 proliferation over 7 days. Osteogenic performance was assessed by ALP activity at 7, 14, and 21 days, Alizarin Red S mineralisation, and quantification of OCN and RUNX2. CHS-NAC_SF_5HAp-syn showed the highest mineralisation, while selected HAp-com formulations produced the highest OCN levels. NBT assays further revealed composition- and cell phenotype-dependent modulation of superoxide anion generation in THP-1 monocytes and macrophages. Overall, composites incorporating HAp-syn showed the most balanced combination of controlled surface properties, rheological reinforcement, no sustained cytotoxic effects, and enhanced mineralisation, supporting their potential for subchondral bone regeneration.},
}

@article {pmid42768800,
year = {2026},
author = {Huang, ZS and Chen, Y and Du, ZJ and Li, H and Feng, JX and Tang, BW and Yuan, SS and Luan, HC and Quan, WH and Di, JM and Chen, J},
title = {Trimethylamine N-oxide, a Gut Microbiota Metabolite, Promotes Diabetes-Mediated Erectile Dysfunction via a PANoptotic-Like Process Involving Pyroptosis, Apoptosis, and Necroptosis in CCSMCs.},
journal = {Andrology},
volume = {},
number = {},
pages = {},
doi = {10.1111/andr.70385},
pmid = {42768800},
issn = {2047-2927},
support = {81871158//the National Natural Science Foundation of China/ ; 82272840//the National Natural Science Foundation of China/ ; 2023A1515012925//the Natural Science Foundation of Guangdong Province/ ; 2025A1515012423//the Natural Science Foundation of Guangdong Province/ ; 2023A1515012925//the Natural Science Foundation of Guangdong Province/ ; },
abstract = {BACKGROUND: Trimethylamine N-oxide (TMAO), a key metabolite derived from gut microbiota dysbiosis, is known to influence various diabetic vascular complications. However, its specific role and the programmed cell death mechanisms underlying the development of diabetes-mediated erectile dysfunction (DMED) remain to be fully elucidated.

OBJECTIVE: To investigate the mechanism by which TMAO mediates corpus cavernosum smooth muscle cell (CCSMC) dysfunction and promotes DMED in type 1 diabetic rats, with a focus on the involvement of the PI3K/Akt-regulated PANoptotic-like process.

METHODS: A type 1 diabetes-mediated erectile dysfunction (T1DMED) rat model was established. Fecal samples were collected for gut microbiota analysis, and serum TMAO levels were measured. Primary CCSMCs were isolated, and cell purity was confirmed via immunofluorescence and flow cytometry. An in vitro TMAO-induced CCSMC injury model was constructed, followed by transcriptome sequencing to identify differentially expressed genes (DEGs) and enriched KEGG signaling pathways. Western blotting and immunohistochemistry (IHC) were performed to detect markers of a PANoptotic-like process (encompassing pyroptosis, apoptosis, and necroptosis) and pathway proteins in penile tissues. Human single-cell RNA sequencing (scRNA-seq) data from penile cavernous tissues were analyzed to compare the PI3K/Akt axis and the PANoptotic-like process-related genes in CCSMCs between DMED patients and healthy controls. TMAO-injured CCSMCs were treated with the ROS scavenger N-acetylcysteine (NAC) and the PI3K/Akt inhibitor LY294002. Flow cytometry and Western blotting were used to quantify markers of this death program and pathway activity.

RESULTS: T1DMED rats exhibited reduced gut microbiota diversity, with Dorea as the dominant genus. Serum TMAO levels were significantly elevated in the ED group compared with the normal and diabetic non-ED groups. Parabacteroides was positively correlated with TMAO levels, whereas Oscillospira showed a negative correlation. Transcriptome sequencing of TMAO-treated CCSMCs revealed significant enrichment of the PI3K/Akt signaling pathway. IHC and Western blotting confirmed the marked activation of the PANoptotic-like process in penile tissues of T1DMED rats. Analysis of human scRNA-seq data revealed significant upregulation of PI3K/Akt signaling and genes associated with the PANoptotic-like program (e.g., CASP1, CASP3, CASP8, and MLKL) in CCSMCs from DMED patients. Flow cytometry demonstrated increased Caspase-1 and Caspase-3 positivity in TMAO-treated CCSMCs. NAC significantly reduced both readouts, whereas LY294002 significantly reduced Caspase-3 positivity but not Caspase-1 positivity. Western blotting confirmed that PI3K and PANoptotic-like markers were upregulated in TMAO-treated CCSMCs, while α-SMA and eNOS were downregulated. NAC treatment attenuated the TMAO-induced oxidative stress cascade, leading to a reduction in these death markers and restoration of α-SMA/eNOS expression. Similarly, LY294002 attenuated several TMAO-induced molecular changes associated with the PANoptotic-like process and partially restored the expression of CCSMC-associated functional markers.

CONCLUSION: Gut microbiota dysbiosis in T1DMED rats was associated with elevated serum TMAO, and TMAO triggered a PANoptotic-like process in CCSMCs via PI3K/Akt activation, thereby contributing to the progression of DMED.},
}

@article {pmid42770049,
year = {2026},
author = {Mahapatra, PD and Bhat, VV and Vyas, NA and Dharmadhikari, S and Puppalwar, G and Khandhedia, C and Mane, A and Mehta, S},
title = {Evaluating the Therapeutic Potential of Antioxidants in Polyendocrine Metabolic Ovarian Syndrome (PMOS)-Associated Infertility.},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {619132},
pmid = {42770049},
issn = {1179-1411},
abstract = {INTRODUCTION: Polyendocrine Metabolic Ovarian syndrome (PMOS) formerly known as polycystic ovarian syndrome (PCOS) constitutes the most common endocrinopathy in women of reproductive age group. Evidence from numerous studies in PMOS patients suggests that antioxidants can modulate the ovarian microenvironment, promote folliculogenesis, and increase oocyte competence and yield. This review aims to summarize the existing clinical evidence regarding the application of antioxidants as adjunctive treatment options in the management of PMOS-related infertility.

MATERIALS AND METHODS: This is a structured narrative review. A literature search (1990-2024) was conducted through PubMed, Google Scholar, and Cochrane Library to identify clinical trials evaluating the role of antioxidants specifically Coenzyme Q10 (CoQ10), N-acetylcysteine (NAC), melatonin, and astaxanthin (AST) in PMOS. Studies were identified and screened based on the predefined eligibility criteria. Inclusion criteria were full-text, English-language studies assessing antioxidant interventions in PMOS or related mechanisms; exclusions were reviews, meta-analyses, animal studies, duplicates, and non-English articles. Of 198 records screened, 28 studies met eligibility criteria and were included in this review.

RESULTS: Based on the data included in our review, the available evidence suggests that CoQ10 enhances mitochondrial function and reduces oxidative stress (OS). It has been reported to increase clinical pregnancy rates, improve insulin sensitivity, sex hormone levels, and blood lipids. N-acetylcysteine scavenges free radicals, provides cysteine for glutathione synthesis, breaks disulfide linkages and reduces OS. It may help to improve pregnancy rates, insulin sensitivity, and metabolic parameters. Additionally, it enhances oocyte quality and supports detoxification. Astaxanthin is a potent antioxidant with anti-inflammatory properties and reduces OS, with the potential to improve the development of follicles and oocytes, insulin sensitivity, lipid parameters, and supports mitochondrial health and cellular function. Melatonin regulates circadian rhythms and reduces OS, helps restore regular menstrual cycles, reduces hyperandrogenism, may improve insulin sensitivity and enhance fertility.

CONCLUSION: Antioxidant supplementation may have a complementary role in improving reproductive outcomes in infertile women with PMOS. However, some uncertainty remains given the heterogeneity of the included studies and the limited number of trials for certain antioxidants. Further well-designed randomized controlled studies are required to establish definitive clinical benefit.},
}

@article {pmid42771058,
year = {2026},
author = {Li, J and Chiew, AL and Isbister, GK and Duffull, SB},
title = {A systems pharmacology model for paracetamol overdose and treatment.},
journal = {Journal of pharmacokinetics and pharmacodynamics},
volume = {53},
number = {6},
pages = {},
pmid = {42771058},
issn = {1573-8744},
support = {2022/GNT2016380//NHMRC Investigator Grant/ ; },
mesh = {*Acetaminophen/pharmacokinetics/adverse effects/poisoning ; *Drug Overdose/drug therapy/metabolism ; *Acetylcysteine/therapeutic use/pharmacology ; Humans ; *Chemical and Drug Induced Liver Injury/drug therapy/metabolism/etiology ; *Antidotes/therapeutic use/pharmacology ; *Models, Biological ; *Analgesics, Non-Narcotic/pharmacokinetics ; Biomarkers/metabolism ; },
abstract = {Paracetamol overdose is the leading cause of acute liver failure in many countries, including North America and the United Kingdom. While timely administration with the standard treatment is generally effective, the optimal treatment for scenarios such as "massive" overdose or modified release paracetamol overdose remains unknown. In this work we aim to develop and calibrate a systems pharmacology model for paracetamol-induced hepatotoxicity with the influence of administration of the antidote N-acetylcysteine (NAC). The system model integrates five components, including (1) input of paracetamol, (2) paracetamol metabolism of parent drug and metabolites, (3) physiological turnover of endogenous sulfur-containing substrates, including the metabolism of cysteine to produce glutathione and inorganic sulfate, etc., (4) a general model for the release of biomarkers from injured hepatocytes to blood, and (5) a PK model for NAC and three proposed mechanisms of NAC effect. The final systems model demonstrated a good description of the concentration-time courses of paracetamol, its metabolites and biomarkers after administration of a normal dose to a large overdose of paracetamol. The final model provides a quantitative and comprehensive understanding of the causal pathway of paracetamol-induced liver toxicity and its treatment, which allows the investigation of the 'what if' scenarios in the rescue of paracetamol poisoning.},
}

*Acetaminophen/pharmacokinetics/adverse effects/poisoning
*Drug Overdose/drug therapy/metabolism
*Acetylcysteine/therapeutic use/pharmacology
Humans
*Chemical and Drug Induced Liver Injury/drug therapy/metabolism/etiology
*Antidotes/therapeutic use/pharmacology
*Models, Biological
*Analgesics, Non-Narcotic/pharmacokinetics
Biomarkers/metabolism

@article {pmid42759906,
year = {2026},
author = {Zhang, Y and Li, X and Shen, Y and Yang, L and Yang, M and Meng, X and Al-Hamyari, B and Shi, Y and Meng, S},
title = {Low-dose polysaccharides exert dual redox effects via the ROS-mediated MAPK pathway: Antioxidant alone or pro-oxidant when GLP is combined with doxorubicin in A2780 ovarian cancer cells.},
journal = {Cellular signalling},
volume = {},
number = {},
pages = {112903},
doi = {10.1016/j.cellsig.2026.112903},
pmid = {42759906},
issn = {1873-3913},
abstract = {Ovarian cancer (OC) is a lethal gynecological malignancy. Patients usually consume low doses of natural polysaccharides through their diet as exogenous antioxidants. This study aims to explore the dual effects of low doses of five natural polysaccharides (GLP, LBP, LNT, APS, FUC) on A2780 OC cells, as well as the underlying molecular mechanisms. The redox effects of their individual actions and the combined action of GLP and doxorubicin (DOX) were evaluated by ROS, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) assays; their growth/apoptosis effects were assessed by MTT, colony formation and flow cytometry. Network pharmacology predicted the MAPK pathway, which was verified by Western blot. In vivo, a xenograft model was established to evaluate the effect of the combination of GLP and DOX. The results showed that low doses of polysaccharides reduced ROS levels, promoted cell viability and colony-forming capacity, upregulated p-ERK levels, and downregulated p-p38 and p-JNK. In vitro, the same dose of GLP combined with DOX increased ROS levels, inhibited cell growth, induced apoptosis, and activated all three MAPK subfamilies. The ROS scavenger N-acetylcysteine (NAC) reversed these effects. In vivo, GLP combined with DOX synergistically inhibited tumor growth. Low doses of natural polysaccharides have specific dual effects: when used alone, they have antioxidant effects, but when GLP is combined with DOX, they have pro-oxidant and tumor-suppressive effects. Both of these effects are mediated through the ROS-MAPK pathway. This provides an experimental basis for mechanism studies and clinical applications of chemotherapy combined with polysaccharides in epithelial OC.},
}

@article {pmid42764870,
year = {2026},
author = {Li, ZR and Zheng, Y and Han, C and Wang, L},
title = {Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line.},
journal = {Iranian journal of medical sciences},
volume = {51},
number = {8},
pages = {570-581},
pmid = {42764870},
issn = {1735-3688},
mesh = {*Reactive Oxygen Species/metabolism ; *Janus Kinase 2/antagonists & inhibitors/metabolism/drug effects ; Humans ; *STAT3 Transcription Factor/metabolism/drug effects ; *Apoptosis/drug effects ; Cell Line, Tumor ; Animals ; Zebrafish ; Signal Transduction/drug effects ; *Cell Cycle Checkpoints/drug effects ; *Lung Neoplasms/drug therapy ; Cell Survival/drug effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; },
abstract = {BACKGROUND: Large cell lung carcinoma (LCLC) is an aggressive non-small cell lung cancer subtype. Mulberrofuran G (MG) from Morus alba L. possesses pharmacological properties, but its anticancer mechanisms in LCLC remain unexplored. This study aimed to validate the antitumor activity of MG against NCI-H460 cells and elucidate its dual mechanism involving Janus kinase 2 (JAK2) inhibition and reactive oxygen species (ROS) induction.

METHODS: This study was conducted at the Nanjing University of Chinese Medicine and China Pharmaceutical University, Nanjing, China, from 2023 to 2025. Cell viability was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Flow cytometry using annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) measured apoptosis, cell cycle, ROS, and mitochondrial membrane potential (MMP). Western blot analyzed p21, cyclin B1, caspases3/7/9, cleaved caspases3/7/9, poly(ADP-ribose) polymerase (PARP), cleaved PARP, JAK2, p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3. Interactions were confirmed via docking, cellular thermal shift assay, and ADP-Glo. In vivo efficacy was evaluated in zebrafish. Data analysis was performed using GraphPad Prism 8.0. Statistical significance was determined using Student's t test or one-way/two-way ANOVA followed by Tukey's post hoc test (P<0.05).

RESULTS: MG suppressed proliferation (IC50=9.90 μM), induced G2/M arrest, and triggered mitochondrial apoptosis. MG inhibited JAK2/STAT3 via direct kinase inhibition (IC50=17.17 μM) and ROS-mediated suppression. N-acetylcysteine (NAC) reversed these effects. Zebrafish tumor growth decreased by 19.7% (P<0.05).

CONCLUSION: MG exerts anticancer effects against LCLC by inducing ROS accumulation and dual suppression of the JAK2/STAT3 pathway, highlighting its potential as a therapeutic candidate.},
}

*Reactive Oxygen Species/metabolism
*Janus Kinase 2/antagonists & inhibitors/metabolism/drug effects
Humans
*STAT3 Transcription Factor/metabolism/drug effects
*Apoptosis/drug effects
Cell Line, Tumor
Animals
Zebrafish
Signal Transduction/drug effects
*Cell Cycle Checkpoints/drug effects
*Lung Neoplasms/drug therapy
Cell Survival/drug effects
Carcinoma, Non-Small-Cell Lung/drug therapy

@article {pmid42753170,
year = {2026},
author = {Pillai, NR and Elsbecker, SA and McCarthy, GB and Weisshappel, K and Karachunski, P and Scaglia, F},
title = {L-Cysteine and N-Acetylcysteine Supplementation Improves Clinical Outcome in a Patient With COXPD10.},
journal = {American journal of medical genetics. Part A},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajmg.a.70299},
pmid = {42753170},
issn = {1552-4833},
abstract = {MTO1 is a nuclear gene that encodes a mitochondrial protein essential for modifying mitochondrial transfer RNAs (tRNAs) and stabilizing codon-anticodon interactions to ensure accurate and efficient mitochondrial protein synthesis and oxidative phosphorylation. Mitochondrial tRNA translation optimization 1 (MTO1) plays an important role in the mitochondrial tRNA taurinomethylation modification by using the amino acid taurine, obtained from cysteine metabolism, at the wobble position U34 of the anticodon loop. Biallelic pathogenic variants in MTO1 cause combined oxidative phosphorylation deficiency 10 (COXPD10) (OMIM#614702). In the severe end of the spectrum, COXPD10 is characterized by infantile-onset hypertrophic cardiomyopathy and lactic acidosis with perinatal mortality when associated with nonsense and frameshift variants. The extra cardiac phenotypes include muscle hypotonia, feeding difficulties, psychomotor delay, optic atrophy, encephalopathy, and seizures. Currently, there is no targeted treatment for this condition aside from supportive care. Herein, we report a 22-month-old child, diagnosed early with a genotype predictive of severe COXPD10, who was initiated on treatment with L-cysteine and N-acetylcysteine (NAC) early in life and did not develop cardiac manifestations. This outcome suggests a potential benefit and improved clinical outcome with early disease-specific treatment initiation.},
}

@article {pmid42757872,
year = {2026},
author = {Xu, Y and Pang, X},
title = {Mechanism of IH promoting pulmonary arterial hypertension through ROS-NLRP3 inflammasome mediated endothelial cell pyroptosis.},
journal = {Experimental lung research},
volume = {52},
number = {1},
pages = {196-206},
doi = {10.1080/01902148.2026.2704400},
pmid = {42757872},
issn = {1521-0499},
mesh = {*Pyroptosis/physiology ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Reactive Oxygen Species/metabolism ; *Inflammasomes/metabolism ; *Endothelial Cells/metabolism ; Humans ; Rats ; *Hypoxia/complications/metabolism ; Male ; Rats, Sprague-Dawley ; *Pulmonary Arterial Hypertension/metabolism/etiology ; },
abstract = {OBJECTIVE: To investigate the mechanism by which Intermittent Hypoxia (IH) promotes Pulmonary Arterial Hypertension (PAH), focusing on ROS-NLRP3 inflammasome-mediated endothelial cell pyroptosis.

METHODS: Human Pulmonary Microvascular Endothelial Cells (HPMECs) and a monocrotaline-induced PAH rat model were exposed to an IH environment. Interventions included the ROS inhibitor N-acetylcysteine (NAC) and the NLRP3 inhibitor MCC950. Assessments measured cell survival, LDH activity, ROS levels, apoptosis, inflammatory cytokines (IL-1β, IL-18), and protein expression of NLRP3 inflammasome components. In rats, hemodynamics, right ventricular hypertrophy, and pulmonary vascular remodeling were evaluated.

RESULTS: IH exposure significantly decreased HPMEC survival and increased LDH activity, ROS levels, apoptosis rate, and the expression of NLRP3, Caspase-1, and ASC proteins. These effects, along with elevated IL-1β and IL-18, were reversed by NAC and MCC950 treatment. In PAH rats, IH exacerbated right ventricular systolic pressure, pulmonary artery pressure, vascular remodeling, and serum inflammatory markers, which were similarly ameliorated by NAC and MCC950.

CONCLUSION: IH promotes the progression of PAH by inducing endothelial cell pyroptosis through the activation of the ROS-NLRP3 inflammasome pathway.},
}

*Pyroptosis/physiology
Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Reactive Oxygen Species/metabolism
*Inflammasomes/metabolism
*Endothelial Cells/metabolism
Humans
Rats
*Hypoxia/complications/metabolism
Male
Rats, Sprague-Dawley
*Pulmonary Arterial Hypertension/metabolism/etiology

@article {pmid42759637,
year = {2026},
author = {Wang, G and Ba, R and Liu, B and Wang, Y and Niu, S and Wan, H and Du, Y and Yu, F and Zhou, G and Zhu, J and Ba, Y},
title = {Fluoride-induced testicular spermatogenic dysfunction: The pivotal role of the AIM2-mediated caspase-3/GSDME pyroptosis pathway.},
journal = {Chemico-biological interactions},
volume = {439},
number = {},
pages = {112346},
doi = {10.1016/j.cbi.2026.112346},
pmid = {42759637},
issn = {1872-7786},
abstract = {Endemic fluorosis from high-fluoride groundwater is a global concern. While fluoride exposure is linked to male infertility, the mechanisms remain unclear. This study utilized male Sprague-Dawley (SD) rats and in vitro immortalized human testicular Sertoli (iHTS) cells to investigate the potential mechanisms underlying sodium fluoride (NaF)-induced testicular damage. In vivo, three-month NaF exposure caused testicular tissue disorganization, decreased sperm viability and motility, and increased sperm abnormalities. Furthermore, NaF exposure significantly altered the oxidative stress status in the rat testis, evidenced by decreased total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione (GSH) levels, along with increased malondialdehyde (MDA) content. Meanwhile, levels of pyroptosis-related proteins (AIM2, Cleaved Caspase-3, GSDME, and GSDME-N), as well as LDH, interleukin (IL)-1β, and IL-18, were significantly increased. Similar results were observed in vitro. Interestingly, knocking down AIM2 in NaF-treated iHTS cells significantly decreased the levels of Cleaved Caspase-3, GSDME, GSDME-N, IL-1β, IL-18, and LDH. Furthermore, inhibiting NaF-induced oxidative stress with N-acetylcysteine (NAC) effectively mitigated these NaF-induced protein and biochemical alterations. These findings suggest that excessive fluoride exposure induces oxidative stress in testicular tissue and cells, subsequently activating the AIM2/Caspase-3/GSDME pyroptotic axis, thereby leading to testicular damage.},
}

@article {pmid42746002,
year = {2026},
author = {Shi, BY and Hu, XD and Liu, YC and Hu, SM and Zhang, GX},
title = {Activation of aryl hydrocarbon receptor by cigarette smoke induces oxidative stress, autophagy impairment and cellular senescence.},
journal = {Tobacco induced diseases},
volume = {24},
number = {},
pages = {},
pmid = {42746002},
issn = {1617-9625},
abstract = {INTRODUCTION: Cellular senescence is a core pathogenic mechanism of chronic obstructive pulmonary disease (COPD), and cigarette smoke (CS) acts as its primary risk factor. However, the molecular cascade linking CS exposure to pulmonary cellular senescence remains poorly defined. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor triggered by CS-derived chemicals, has an unclarified function in smoke-induced lung cell senescence. This study aimed to verify whether AhR mediates CS-elicited pulmonary senescence through regulating oxidative stress and autophagy, and to elucidate the complete downstream signaling cascade.

METHODS: We established an 8-week whole-body CS exposure rat COPD model and treated human bronchial epithelial BEAS-2B cells with cigarette smoke extract (CSE). Multiple detection approaches were applied to assess lung pathological lesions, cellular senescence, autophagic flux and intracellular reactive oxygen species (ROS). We further performed transcriptomic sequencing on rat lung tissues and mined three public human COPD Gene Expression Omnibus (GEO) datasets to screen key differential genes. Rescue experiments with rapamycin (autophagy activator), N-acetylcysteine (NAC, ROS scavenger) and CH223191 (specific AhR antagonist) were conducted to validate causal relationships among AhR, ROS, autophagy and senescence.

RESULTS: In vivo CS exposure induced typical COPD-like pathological alterations and prominent cellular senescence in rat lungs. In vitro CSE treatment triggered dose-dependent senescence in BEAS-2B cells, accompanied by impaired autophagic flux and excessive ROS overproduction; rapamycin and NAC separately reversed these two phenotypes. Both in vivo and in vitro data confirmed robust activation of the AhR pathway, evidenced by significant upregulation of AhR target genes CYP1A1 and CYP1B1. Pharmacological inhibition of AhR via CH223191 suppressed ROS accumulation, restored defective autophagy, and ultimately alleviated CSE-induced cellular senescence.

CONCLUSIONS: CS activates pulmonary AhR signaling, which sequentially drives excessive ROS generation, autophagic flux impairment and irreversible lung epithelial senescence. The AhR-ROS-autophagy axis represents a novel pathogenic pathway mediating smoke-related lung aging.},
}

@article {pmid42748693,
year = {2026},
author = {Gaweł, M and Głowacki, R and Piechocka, J},
title = {Analysis of berry superfruits for reduced and total thiol content by LC-UV-based methods.},
journal = {Food chemistry},
volume = {529},
number = {},
pages = {151137},
doi = {10.1016/j.foodchem.2026.151137},
pmid = {42748693},
issn = {1873-7072},
abstract = {The article presents the first methods for determining total and reduced glutathione (GSH), cysteine (Cys), cysteinyl-glycine (Cys-Gly), and homocysteine (Hcy) in berries using high-performance liquid chromatography with ultraviolet detection. The assay employs N-acetyl-cysteine as an internal standard. Sample preparation involves homogenization in phosphate buffer, tris(2-carboxyethyl)phosphine-mediated reduction of disulfide bonds (if total thiol content is determined), 2-chloro-1-methylquinolinium tetrafluoroborate derivatization, perchloric acid acidification, and filtration through a polyethersulfone membrane. Separation is achieved on a Zorbax SB-C18 column using gradient elution with trichloroacetic acid and acetonitrile. Both total and reduced thiol assays showed linearity at 0.5-50 μmol/L for GSH and 0.5-20 μmol/L for Cys and Cys-Gly. Applied to various Polish market berries (e.g., strawberry, raspberry, blueberry, blackberry, forest berry, haskap berry, wild strawberry, currant, gooseberry, cranberry, chokeberry, and elderberry) results identified GSH as the predominant thiol. Cys appeared at lower levels, Cys-Gly was found in traces, and Hcy was undetected.},
}

@article {pmid42751421,
year = {2026},
author = {Elgharbawy, FM and Bayoumi, MAA and Ajele, KW and Lwaleed, BA},
title = {Fetal and neonatal effects of N-acetylcysteine for maternal chorioamnionitis: a systematic review.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1819220},
pmid = {42751421},
issn = {2296-2360},
abstract = {BACKGROUND: Maternal chorioamnionitis (mCA) and intra-amniotic infection/inflammation (Triple I) are major causes of fetal inflammatory injury and are associated with preterm birth, white matter injury, cerebral palsy, bronchopulmonary dysplasia (BPD), and necrotising enterocolitis (NEC). No established therapy directly targets the inflammatory and oxidative pathways underlying fetal neuroinjury. N-acetylcysteine (NAC), a glutathione precursor with antioxidant and anti-inflammatory properties, has emerged as a potential adjunctive neuroprotective therapy, although human evidence remains limited.

OBJECTIVE: To evaluate fetal and neonatal outcomes associated with antenatal or intrapartum NAC administration in pregnancies complicated by mCA or Triple I.

METHODS: A systematic review was conducted using MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov from inception to December 23, 2025. Eligible studies included randomised controlled trials, prospective cohorts, non-randomised studies, and translational animal models evaluating NAC exposure in mCA or Triple I. Clinical outcomes, biomarkers, pharmacokinetics, and mechanistic pathways were synthesised narratively. Risk of bias was assessed using RoB 2, ROBINS-I, and SYRCLE tools.

RESULTS: Ten studies met the inclusion criteria, including five human and six translational animal studies. Human evidence involved approximately 143 mother-infant dyads. NAC exposure was associated with preserved cerebrovascular coupling, improved delivery-room adaptation, reduced severe neonatal morbidity, and lower BPD rates without major safety concerns. Pharmacokinetic studies demonstrated rapid placental transfer and gestation-dependent neonatal clearance. Animal studies consistently showed reductions in inflammatory cytokines, oxidative stress, apoptosis, and microstructural brain injury.

CONCLUSION: NAC demonstrates biologically plausible neuroprotective potential in mCA and Triple I; however, the evidence remains preliminary due to small sample sizes and heterogeneous protocols. However, some studies showed no or negative effects. Large multicenter randomised trials with standardised dosing and long-term neurodevelopmental follow-up are needed before routine clinical implementation can be recommended.},
}

@article {pmid42738792,
year = {2026},
author = {Nguyen, VDA and Tran, YTH and Mangelings, D and Heyden, YV and Van Eeckhaut, A and Tran, HTM},
title = {Fungal Melanins as Potential Reactive Oxygen Species-Scavenging Neuroprotective Agents.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {17},
pages = {},
pmid = {42738792},
issn = {1420-3049},
support = {VN2022TEA534A105//VLIR-UOS/ ; },
mesh = {*Melanins/pharmacology/chemistry ; *Neuroprotective Agents/pharmacology/chemistry ; Humans ; *Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; Hydrogen Peroxide/pharmacology/toxicity ; *Free Radical Scavengers/pharmacology/chemistry ; Oxidative Stress/drug effects ; Cell Line, Tumor ; *Fungi/chemistry ; },
abstract = {Oxidative stress is strongly associated with neuronal damage in neurodegenerative diseases, such as Parkinson's disease (PD). Fungal melanins are remarkable free radical scavengers; however, their capacity to protect neurons from reactive oxygen species (ROS)-induced damage remains understudied. This research evaluated the neuroprotective effects of fungal melanins and their arginine-modified counterparts on SH-SY5Y cells against neurotoxins, as well as their impact on ROS levels. Exposure to 0.6 mM H2O2 or 1 mM MPP[+] markedly elevated ROS levels and reduced cell viability to approximately 56% and 60%, respectively. At 10 μg/mL, melanins from Apioperdon pyriforme, Russula nigricans, and Xylaria nigripes significantly protected cells against H2O2 cytotoxicity, whereas arginine-modified melanin from the skin of Scleroderma sinnamariense significantly attenuated MPP[+] cytotoxicity. Further dose-dependent evaluation revealed that melanin from A. pyriforme (10-12 μg/mL) displayed activity comparable to the positive control (164 μg/mL N-Acetylcysteine (NAC)) against H2O2 by increasing cell viability up to 90%. Similarly, arginine-modified melanin from S. sinnamariense (6-10 μg/mL) and NAC showed a comparable protective effect against MPP[+], boosting cell viability up to 80%. Both samples suppressed ROS to levels comparable to, or lower than, the untreated control. Melanin from A. pyriforme is a promising candidate for further research into complementary therapies for PD.},
}

*Melanins/pharmacology/chemistry
*Neuroprotective Agents/pharmacology/chemistry
Humans
*Reactive Oxygen Species/metabolism
Cell Survival/drug effects
Hydrogen Peroxide/pharmacology/toxicity
*Free Radical Scavengers/pharmacology/chemistry
Oxidative Stress/drug effects
Cell Line, Tumor
*Fungi/chemistry

@article {pmid42739055,
year = {2026},
author = {Greco, S and Delli Carpini, G and Duménigo Gonzàlez, A and Goteri, G and Ciavattini, A and Ciarmela, P},
title = {Modulating the Estrobolome and Inflammatory Microenvironment in Endometriosis: The Role of Microbiome-Targeted Interventions and Nutritional Compounds.},
journal = {Nutrients},
volume = {18},
number = {17},
pages = {},
pmid = {42739055},
issn = {2072-6643},
mesh = {Humans ; Female ; *Endometriosis/microbiology/therapy/metabolism ; *Estrogens/metabolism ; Animals ; Probiotics ; *Gastrointestinal Microbiome/drug effects ; Inflammation ; Prebiotics/administration & dosage ; Dysbiosis ; Microbiota ; },
abstract = {Endometriosis is a chronic estrogen-dependent systemic inflammatory disorder characterized by ectopic implantation of endometrial-like tissue, primarily on the ovaries, pelvic peritoneum, and bowel. According to the World Health Organization (WHO) estimate updated in 2025, endometriosis affects approximately 10% (about 190 million) of reproductive-age women worldwide and is a major contributor to chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Standard medical therapies focus on ovarian suppression, which alleviates symptoms but precludes conception and carries significant metabolic and skeletal adverse effects. Recent multi-omics research has raised interest in the gut microbiome and the estrobolome, defined as the microbial gene repertoire involved in estrogen metabolism, as potential modulators of systemic estrogen exposure and immune homeostasis. Altered microbiota composition and microbial β-glucuronidase activity may influence enterohepatic estrogen recirculation; however, endometriosis-specific evidence is predominantly associative or preclinical and does not establish a causal pathway. Dysbiosis and increased bacterial β-glucuronidase activity promote enterohepatic recirculation of estrogens, contributing to hyperestrogenism and ectopic lesion proliferation. Concurrently, oxidative stress, peritoneal inflammation, aberrant macrophage polarization, and neoangiogenesis sustain lesion survival and contribute to chronic pelvic pain. This comprehensive review synthesizes mechanistic, preclinical, and clinical evidence regarding microbiome-targeted interventions and nutritional compounds, including probiotics, prebiotics, N-acetyl cysteine (NAC), curcumin, resveratrol, epigallocatechin gallate (EGCG), omega-3 polyunsaturated fatty acids (PUFAs), and vitamin D, in modulating the estrobolome, immune responses, and oxidative microenvironment in endometriosis. We further discuss dietary patterns, bioavailability challenges, and the potential of precision nutrition to optimize reproductive outcomes. These approaches may be considered complementary or investigational adjuncts; current evidence is insufficient to demonstrate disease modification or improvements in spontaneous pregnancy, assisted reproductive technology (ART) outcomes, or live birth. Here, "fertility-sparing" denotes the absence of intentional ovulation suppression rather than proven fertility enhancement.},
}

Humans
Female
*Endometriosis/microbiology/therapy/metabolism
*Estrogens/metabolism
Animals
Probiotics
*Gastrointestinal Microbiome/drug effects
Inflammation
Prebiotics/administration & dosage
Dysbiosis
Microbiota

@article {pmid42745677,
year = {2026},
author = {Liu, F and Zhong, A and Li, J and Sun, Q and Fan, X and Fan, W and Tong, X and Liang, Y and Wang, X and Huang, D and Zhang, Y and Gao, F and Lu, B and Wang, B},
title = {Melatonin Alleviates Diabetic Cardiomyopathy by Inhibiting Cellular Senescence via Activation of the MT2/SIRT1/Nrf2 Signaling Pathway.},
journal = {Journal of pineal research},
volume = {78},
number = {5},
pages = {e70185},
pmid = {42745677},
issn = {1600-079X},
support = {81703508//National Natural Science Foundation of China/ ; 2025A1515012603//Guangdong Basic and Applied Basic Research Foundation/ ; B2026030//Medical Scientific Research Foundation of Guangdong Province/ ; },
mesh = {Animals ; *Melatonin/pharmacology ; *NF-E2-Related Factor 2/metabolism/genetics ; *Sirtuin 1/metabolism ; *Diabetic Cardiomyopathies/metabolism/drug therapy/pathology ; *Signal Transduction/drug effects ; *Cellular Senescence/drug effects ; Mice ; Rats ; *Receptor, Melatonin, MT2/metabolism ; Male ; Diabetes Mellitus, Experimental/metabolism/drug therapy ; Myocytes, Cardiac/metabolism/drug effects ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; },
abstract = {Diabetic cardiomyopathy (DCM) is one of the most severe cardiovascular complications of diabetes mellitus (DM), yet effective treatment strategies remain lacking. Cellular senescence is a principal risk factor for multiple cardiovascular diseases, contributing significantly to cardiac dysfunction and disease progression. Melatonin, an endogenous hormone primarily secreted by the pineal gland, exerts cardioprotective effects against DCM. However, the underlying molecular mechanism remains incompletely understood, particularly whether melatonin ameliorates DCM by suppressing cardiomyocyte senescence. In this study, a streptozotocin (STZ)‑induced diabetic mouse model in vivo and an in vitro model of high‑glucose (HG)‑treated primary neonatal rat cardiomyocytes (NRCMs) were established. Melatonin ameliorated cardiac dysfunction in diabetic mice and alleviated the senescence phenotype in cardiomyocytes. Suppressing oxidative stress with the ROS scavenger N-acetylcysteine (NAC) effectively attenuated cardiomyocyte senescence, confirming the causal role of oxidative stress in senescence progression under HG conditions. Mechanistically, melatonin effectively upregulated the expression of melatonin receptor 1B (MT2), thereby activating the SIRT1/Nrf2 signaling pathway and promoting Nrf2 nuclear translocation. Notably, genetic ablation of Nrf2 in diabetic mice, as well as pharmacological inhibition of MT2, SIRT1, or Nrf2 in NRCMs, substantially abolished the protective effects of melatonin. Collectively, melatonin alleviates DCM by attenuating oxidative stress-induced cellular senescence through activation of the MT2/SIRT1/Nrf2 signaling pathway. These findings uncover a novel mechanism underlying the cardioprotective action of melatonin against DCM.},
}

Animals
*Melatonin/pharmacology
*NF-E2-Related Factor 2/metabolism/genetics
*Sirtuin 1/metabolism
*Diabetic Cardiomyopathies/metabolism/drug therapy/pathology
*Signal Transduction/drug effects
*Cellular Senescence/drug effects
Mice
Rats
*Receptor, Melatonin, MT2/metabolism
Male
Diabetes Mellitus, Experimental/metabolism/drug therapy
Myocytes, Cardiac/metabolism/drug effects
Oxidative Stress/drug effects
Mice, Inbred C57BL

@article {pmid42736454,
year = {2026},
author = {Zhao, QQ and Zhao, Y and Fan, SJ and Jiang, YC and Zheng, TH and Bao, SJ and Xu, DY and Zheng, ZZ and Jin, YH and Wang, Y and Chong, SY and Liang, G and Zhu, H},
title = {The deubiquitinase YOD1 in renal tubular epithelial cells promotes diabetic kidney disease by stabilizing KEAP1.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
pmid = {42736454},
issn = {1745-7254},
abstract = {Renal tubular epithelial cell (RTEC) injury is an early event in diabetic kidney disease (DKD) and is a key driver of its development and progression. Deubiquitinating enzymes (DUBs) play crucial roles in the progression of diseases by regulating the stability of substrate proteins. This study aims to elucidate the regulatory role and underlying mechanisms of the deubiquitinating enzyme ovarian tumor domain-containing 2 (YOD1) in RTEC injury and DKD. Through transcriptomics and single-cell mRNA sequencing, we confirmed that YOD1 expression is upregulated in diabetic kidneys and that YOD1 is predominantly localized in RTECs. RTEC-specific Yod1 knockout alleviates renal injury in diabetic mice. RNA-seq analysis revealed a positive correlation between YOD1 and the oxidative stress signaling pathway. Interactome analysis revealed the oxidative stress regulatory protein Kelch-like ECH-associated protein 1 (KEAP1) as a YOD1 substrate. YOD1 deubiquitinates and stabilizes KEAP1, which suppresses NRF2 nuclear translocation under high glucose and palmitic acid (HG/PA) stimulation, thus increasing oxidative stress. Similarly, the ROS scavenger N-acetylcysteine (NAC) can alleviate oxidative stress injury to some extent by reducing ROS levels in RTECs. Finally, we confirmed that the YOD1 pharmacological inhibitor G5 has therapeutic effects on kidney injury in diabetic mice. Our findings demonstrate that the YOD1-KEAP1 axis mediates oxidative stress injury in RTECs and highlight that targeting YOD1 represents a potential treatment approach for DKD.},
}

@article {pmid42736670,
year = {2026},
author = {Mohanbabu, J and Manogaran, A and Srinivasan, SHK and Rohith, AP and Anand, K and Rajanandh, MG},
title = {Effect of N-Acetylcysteine in Reducing Postoperative Cognitive Dysfunction after Anaesthesia in Elderly Patients Undergoing Day Surgery: A Randomized Controlled Study.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273485933260821105708},
pmid = {42736670},
issn = {1996-3181},
abstract = {INTRODUCTION: Postoperative cognitive dysfunction (POCD) refers to a decline in cognitive ability following surgery. N-acetylcysteine (NAC) has antioxidant and neuroprotective properties; however, clinical evidence supporting its role in reducing POCD in elderly patients undergoing day surgery remains limited. This study evaluated the effect of oral NAC on POCD recovery among older adults undergoing day surgery.

METHODS: This randomized controlled trial included elderly patients undergoing outpatient surgery with American Society of Anaesthesiologists physical status I-III. Participants received oral NAC (400-600 mg) or placebo. NAC was administered preoperatively and twice daily for two postoperative days. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at baseline (2 hours before surgery) and 24 hours postoperatively. Physiological recovery and readiness for discharge were assessed using the Modified Aldrete Score (MAS), while quality of recovery was evaluated using the Quality of Recovery-40 (QoR-40) questionnaire.

RESULTS: Of 417 randomized patients, 296 were included in the final analysis (148 in each group). Within-group analysis showed no significant change in MoCA scores from baseline to 24 hours postoperatively in either the test group (p = 0.959) or the control group (p = 0.734). No significant between- group difference was observed in MAS (p > 0.05). In contrast, QoR-40 was significantly higher in the Test group compared with the control group (p < 0.05). No drug-related adverse events were observed during the study period.

DISCUSSION: NAC improved quality of recovery but not postoperative cognitive function MoCA. Discharge readiness, MAS is unaffected. Hence, larger and longer follow-up investigations are needed.

CONCLUSION: Oral NAC did not significantly affect early postoperative cognitive or physiological recovery in elderly day-surgery patients but was associated with improved quality of recovery.},
}

@article {pmid42729321,
year = {2026},
author = {Huang, D and Zhou, R and Ling, J},
title = {Astragaloside IV attenuates hypoxia-reoxygenation-induced endothelial senescence and vascular inflammation by modulating the NOTCH1/VCAM-1 axis.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1855522},
pmid = {42729321},
issn = {1663-4365},
abstract = {OBJECTIVE: Alzheimer's disease (AD) progression involves cerebral microvascular endothelial cell senescence induced by brain hypoperfusion, which contributes to blood-brain barrier (BBB) dysfunction. While Notch1 signaling is known to exacerbate endothelial senescence and neuroinflammation via vascular cell adhesion molecule-1 (VCAM-1), the mechanism by which it mediates hypoxia-induced endothelial aging in AD remains unclear. Furthermore, although Astragaloside IV (AS-IV) has been shown to alleviate cerebral hypoperfusion in AD, whether it acts by directly modulating the Notch1/VCAM-1 axis is unknown. This study aimed to determine whether AS-IV mitigates endothelial senescence and AD pathology by modulating the Notch1/VCAM-1 pathway.

METHODS: Transcriptomic analysis of AD patient data and network pharmacology identified NOTCH1 as a key target. Molecular docking and 100-ns molecular dynamics simulations (using Desmond) characterized AS-IV-Notch1 interactions. Human brain microvascular endothelial cells (HBMECs) were subjected to hypoxia-reoxygenation (HR) to model AD-associated hypoperfusion. Cells were treated with AS-IV (25, 50, or 100 μM) or N-acetylcysteine (NAC) as a positive antioxidant control. Notch1 signaling was experimentally modulated using a recombinant decoy receptor to simulate signaling blockade, creating a contrast with HR-induced overactivation. Assessments included CCK-8 assays, MDA and ROS detection, qPCR, and Western blotting.

RESULTS: NOTCH1 expression was upregulated in AD patients. Molecular docking and dynamics simulations predicted a stable binding mode between AS-IV and Notch1. HR exposure significantly increased oxidative stress and upregulated senescence markers (p16, p21, and p53), proinflammatory senescence-associated secretory phenotype (SASP) factors (IL-6, IL-1β, and TNF-α), and Notch1/VCAM-1 expression. Conversely, AS-IV treatment improved cell viability, reduced oxidative stress (with efficacy comparable to NAC), and downregulated Notch1/VCAM-1, senescence, and SASP markers. Notably, perturbing Notch signaling, either through HR-induced overactivation or decoy receptor-mediated blockade, exacerbated the senescent phenotype. Importantly, AS-IV co-treatment effectively rescued cellular damage induced by both forms of Notch pathway dysregulation.

CONCLUSION: AS-IV alleviates HR-induced endothelial senescence by modulating the Notch1/VCAM-1 axis. Our data suggest that AS-IV does not merely inhibit Notch1 but acts by modulating its signaling toward a protective equilibrium, thereby attenuating endothelial senescence and inflammation associated with the restoration of Notch1/VCAM-1 signaling balance. These findings highlight the potential of AS-IV as a therapeutic candidate for AD vascular pathology.},
}

@article {pmid42730465,
year = {2026},
author = {Kumari, R and Jayaraman, GV and Dutta, SK and Pande, A and Vijayakumar, M and Bhupal, VSR and Jariwala, P and Palimkar, P and Rungta, S and Rajani, D and Banerjee, G and Kumar, S and Kothari, DD and Tolchand, JL and Panchal, P and Nagashankar, N},
title = {Dual Antioxidant Supplementation With N-Acetylcysteine and Taurine (Nefrosave[®]) for Cardio-Renal Protection in Chronic Kidney Disease Patients With Diabetes and/or Hypertension: A Real-World, Retrospective, Comparative Study.},
journal = {Cardiology research},
volume = {17},
number = {5},
pages = {437-452},
pmid = {42730465},
issn = {1923-2829},
abstract = {BACKGROUND: Chronic kidney disease (CKD) is a growing global health burden. Type 2 diabetes mellitus (T2DM) and hypertension are predominant etiological factors. Oxidative stress plays a pivotal role, making antioxidant therapies promising. This study evaluated the effectiveness and tolerability of the antioxidant-combination N-acetylcysteine (NAC; 150 mg) and taurine 500 mg (Nefrosave[®]) in patients with CKD having T2DM and/or hypertension.

METHODS: This real-world, retrospective, multicentric study compared electronic medical records (EMRs) of adults with stages 1-3 CKD treated for 12 ± 2 weeks with NAC + taurine plus standard of care (n = 300; test) or standard of care alone (n = 150; control). Endpoints included changes in urinary albumin-to-creatinine ratio (uACR) and serum creatinine (primary), and changes in estimated glomerular filtration rate (eGFR) and adverse events (AEs, secondary).

RESULTS: Mean uACR reduced significantly in the test group (-8.61%; P < 0.001), but increased significantly in the control (+11.26%; P < 0.001). A similar trend was observed for changes in median serum creatinine (-0.05 mg/dL, P < 0.001 vs. +0.15 mg/dL, P < 0.001). eGFR improved in the NAC + taurine group, concomitant with a significant between-group difference of +6 mL/min/1.73 m[2] (P < 0.001). Nephroprotective effects were consistent and favorable across CKD stages. A comparatively higher proportion of patients in the test group achieved ≥ 30% improvement in uACR and serum creatinine, although absolute proportions were low. AEs were infrequent and mild; no serious events occurred.

CONCLUSION: NAC + taurine plus standard of care was more effective than standard of care alone in reducing uACR and improving eGFR. Tolerability was good with minimal AEs, supporting the NAC + taurine combination as a potent nephroprotective therapy in CKD patients having T2DM and/or hypertension.},
}

@article {pmid42732209,
year = {2026},
author = {Monti, DA and Monadi, SD and Mohamed, FB and Alizadeh, M and Zabrecky, G and Wintering, N and Gupta, M and Steinmetz, A and Kremens, D and Bazzan, AJ and Newberg, AB},
title = {PET-MRI effects of N-acetylcysteine in patients with multiple sclerosis.},
journal = {IBRO neuroscience reports},
volume = {21},
number = {},
pages = {747-753},
pmid = {42732209},
issn = {2667-2421},
abstract = {BACKGROUND: The purpose of this study was to explore if administration of N-acetylcysteine (NAC) in patients with multiple sclerosis (MS) resulted in altered neurophysiological function as determined by the combination of functional connectivity (FC) based on resting Blood Oxygen Level Dependent (BOLD) fMRI and cerebral glucose metabolism using Fluorodeoxyglucose Positron Emission Tomography (FDG PET) and whether those changes were associated with improvements in symptoms.

METHODS: Thirty-six patients with mild to moderate MS were randomized to either NAC plus standard of care, or standard of care only. The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500 mg 2x/day) the other six days. Patients in both groups were evaluated initially and after 4 ± 2 months on an integrated PET-MRI platform with resting BOLD fMRI and FDG PET. Clinical symptom questionnaires were also completed at both time points.

RESULTS: The FC data showed significant differences in several brain regions including the inferior frontal gyrus, inferior temporal gyrus, inferior parietal gyrus, insula, cerebellum, and brain stem in the MS group after treatment with NAC. FDG PET demonstrated increased cerebral glucose metabolism in several of these structures including the inferior frontal gyrus and inferior temporal gyrus. Self-reported scores related to cognition and attention significantly correlated with these neurophysiological changes in the NAC group compared to controls.

CONCLUSIONS: The results of this study suggest that NAC administration alters resting functional connectivity along with cerebral glucose metabolism in MS patients, and this is associated with qualitative improvements in cognition and attention.},
}

@article {pmid42715798,
year = {2026},
author = {Xiong, D and Wan, Z and Hu, L and Luo, Y and Tan, Y and Cao, Y and Han, G and Zhang, J},
title = {Perioperative orexin-A protects brain microvascular endothelial integrity in experimental sepsis-associated encephalopathy.},
journal = {Neuropeptides},
volume = {120},
number = {},
pages = {102652},
doi = {10.1016/j.npep.2026.102652},
pmid = {42715798},
issn = {1532-2785},
abstract = {BACKGROUND: Sepsis-associated encephalopathy (SAE) represents a prevalent central nervous system complication in patients with blood-brain barrier (BBB) dysfunction as core pathogenic mechanism. Orexin-A (OXA) modulates inflammatory and oxidative responses, but its direct protective effect on brain microvascular endothelial cells (BMVECs) remains unreported.

METHODS: In vivo, SAE was induced in mice by the cecal ligation and puncture (CLP), lateral ventricular administration of OXA is performed during the perioperative period. Survival, Y-maze, and open-field tests assessed cognition. BBB permeability was evaluated by cerebral water content and extravasation of Evans blue dye. Endothelial junctions, inflammation and neuronal damage were examined via VE-cadherin, ICAM-1/VCAM-1/IL-6, hematoxylin-eosin (HE) and Nissl staining. In vitro, LPS-stimulated bEnd.3 cells were treated with OXA or N-acetylcysteine (NAC). Oxidative stress (ROS, SOD, MDA/GSH), VE-cadherin, Occluding, ZO-1, γH2AX, and NF-κB activation were measured.

RESULTS: OXA improved survival and cognitive performance, reduced BBB permeability, upregulated VE-cadherin expression, suppressed inflammatory responses, and alleviated neuronal damage. In LPS stimulation bEnd.3 cells, OXA and NAC similarly reduced ROS accumulation, restored VE-cadherin. OXA decreased γH2AX, and inhibited NF-κB activation as well as ICAM-1/VCAM-1 expression.

CONCLUSION: OXA pretreatment protects against SAE by attenuating oxidative stress, suppressing NF-κB signaling activation, reducing inflammatory responses, and preserving endothelial junction integrity, including VE-cadherin-mediated adherens junctions, thereby mitigating blood-brain barrier disruption and improving behavioral performance in the CLP-induced SAE model.},
}

@article {pmid42718567,
year = {2026},
author = {Zhang, H and Liu, M and Shi, L and Wang, X and Xie, J and Ma, Q},
title = {Clinical efficacy, safety evaluation, and mechanism of acetylcysteine in improving first-line anti-tuberculosis treatment of newly diagnosed pulmonary TB: an open-label, randomized, single-center trial.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1844872},
pmid = {42718567},
issn = {2296-858X},
abstract = {OBJECTIVE: To investigate the clinical efficacy, safety and mechanism of N-acetylcysteine combined with conventional antituberculosis drugs in the treatment of newly diagnosed pulmonary tuberculosis.

METHODS: A total of 90 newly diagnosed pulmonary tuberculosis patients were randomly assigned to a Control group (n = 30), Aerosol NAC group (n = 30), or Oral NAC group (n = 30). The Control group received standard HRZE therapy, whereas the Aerosol NAC and Oral NAC groups received additional nebulized N-acetylcysteine (300 mg twice daily) or oral N-acetylcysteine (600 mg once daily), respectively. Clinical efficacy, sputum conversion, St. George's Respiratory Questionnaire (SGRQ) scores, liver function indices, oxidative stress biomarkers, inflammatory markers, and adverse events were assessed over 3 months. Data were analyzed using one-way ANOVA, repeated-measures ANOVA, Chi-square tests, and Bonferroni-adjusted post hoc analyses.

RESULTS: Treatment successful response rates were significantly higher in the Aerosol NAC group (96.67%) and Oral NAC group (93.33%) than in the Control group (70.00%) (p < 0.05). At 3 months, sputum conversion rates reached 93.33 and 96.67% in the Aerosol NAC and Oral NAC groups, respectively, compared with 73.33% in the Control group (p < 0.05). Both NAC groups demonstrated significantly lower SGRQ scores, improved liver function parameters (AST, ALT, TBIL, and GGT), higher antioxidant enzyme levels (SOD and GSH-Px), lower MDA concentrations, and reduced inflammatory markers (IFN-γ, PCT, and IL-4) compared with the Control group (all p < 0.05). The incidence of adverse reactions was lower in both NAC groups (10.0%) than in the Control group (40.0%) (p < 0.05).

CONCLUSION: Adjunctive N-acetylcysteine, administered either by aerosol inhalation or orally, significantly improved treatment outcomes, accelerated sputum conversion, reduced oxidative stress and inflammation, protected liver function, and decreased adverse events in patients with newly diagnosed pulmonary tuberculosis.},
}

@article {pmid42720830,
year = {2026},
author = {Zheng, J and Zhang, Q and Wang, L and Yuan, M and Wang, Y and Wei, X and Lian, H and Liu, X and Liu, Y},
title = {p-Coumaric acid inhibits hepatocellular carcinoma through promoting ROS accumulation.},
journal = {Medical oncology (Northwood, London, England)},
volume = {43},
number = {10},
pages = {},
pmid = {42720830},
issn = {1559-131X},
support = {32100008//National Natural Science Foundation of China/ ; 20212BAB216078//Natural Science Foundation of Jiangxi Province/ ; },
mesh = {*Reactive Oxygen Species/metabolism ; Humans ; *Carcinoma, Hepatocellular/metabolism/drug therapy/pathology ; *Liver Neoplasms/metabolism/drug therapy/pathology ; Animals ; *Propionates/pharmacology ; Mice ; Cell Proliferation/drug effects ; Apoptosis/drug effects ; Xenograft Model Antitumor Assays ; Cell Movement/drug effects ; Mice, Nude ; *Coumaric Acids/pharmacology ; Cell Line, Tumor ; Membrane Potential, Mitochondrial/drug effects ; NF-E2-Related Factor 2/metabolism ; Male ; },
abstract = {Hepatocellular carcinoma (HCC) remains one of the most life-threatening diseases. The regulation of redox homeostasis plays a pivotal role in the progression of HCC. p-Coumaric acid (PCA), a naturally occurring compound, exhibits diverse pharmacological activities; however, its potential anti-HCC effects have not been previously reported. This study aimed to investigate the potential anti-HCC effects of PCA, with a focus on its role in modulating reactive oxygen species (ROS) accumulation in HCC cells. The anti-HCC effects of PCA were evaluated through in vitro and in vivo experiments. In vitro assays, including cell growth, proliferation, wound healing, and Transwell migration, assessed PCA's inhibitory effects, while flow cytometry analyzed apoptosis. Mitochondrial function and ROS levels were measured, with the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway's role explored. In vivo, a subcutaneous xenograft mouse model, using NAC as a ROS scavenger, validated PCA's effects. PCA significantly inhibited the growth and proliferation ability of HCC cells. It also impeded cell migration and induced cell shrinkage and apoptosis. Moreover, PCA suppressed the levels of anti-apoptotic and pro-proliferative proteins. From a mechanistic perspective, PCA reduced mitochondrial membrane potential and ATP production, subsequently promoting ROS accumulation. The inhibition of the Nrf2 signaling pathway by PCA further enhanced ROS levels. Hemin, an agonist of the antioxidant enzyme HO-1, counteracts the inhibitory effect of PCA on the viability of HCC cells. And, in vivo experiments demonstrated that the anti-HCC effects of PCA were reversed by N-acetylcysteine, confirming the critical role of ROS in PCA-mediated inhibition of HCC progression. Our findings indicate that PCA suppresses HCC progression by promoting ROS accumulation, suggesting its therapeutic potential for HCC.},
}

*Reactive Oxygen Species/metabolism
Humans
*Carcinoma, Hepatocellular/metabolism/drug therapy/pathology
*Liver Neoplasms/metabolism/drug therapy/pathology
Animals
*Propionates/pharmacology
Mice
Cell Proliferation/drug effects
Apoptosis/drug effects
Xenograft Model Antitumor Assays
Cell Movement/drug effects
Mice, Nude
*Coumaric Acids/pharmacology
Cell Line, Tumor
Membrane Potential, Mitochondrial/drug effects
NF-E2-Related Factor 2/metabolism
Male

@article {pmid42721182,
year = {2026},
author = {Matsunaga, H and Yonemitsu, R and Ideo, K and Ide, J and Shimada, M and Tateyama, M and Tian, X and Takata, S and Takata, K and Tanimura, S and Shibata, Y and Yoshimura, N and Maeda, K and Kawakami, J and Arima, T and Kai, Y and Karata, S and Goshogawa, H and Hisanaga, S and Sugimoto, K and Tanoue, H and Yugami, M and Nakamura, T and Uehara, Y and Masuda, T and Tokunaga, T and Karasugi, T and Miyamoto, T},
title = {N-acetylcysteine attenuates oxidative-stress-associated apoptosis and collagen deposition after rat hindlimb ischemia-reperfusion injury.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0357829},
pmid = {42721182},
issn = {1932-6203},
mesh = {Animals ; *Apoptosis/drug effects ; *Reperfusion Injury/metabolism/drug therapy/pathology ; *Oxidative Stress/drug effects ; *Acetylcysteine/pharmacology ; Rats ; *Collagen/metabolism ; Male ; *Hindlimb/pathology/metabolism/blood supply/drug effects ; Muscle, Skeletal/metabolism/drug effects/pathology ; Hydrogen Peroxide/pharmacology ; Caspase 3/metabolism ; bcl-2-Associated X Protein/metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Antioxidants/pharmacology ; },
abstract = {Proper use of fingers and limbs is crucial for people to carry out normal activities of daily living. Therefore, when fingers or limbs are severed accidentally, replantation is attempted whenever possible. However, even when replantation is successful and fingers or limbs are preserved, functional limitations often arise due to contractures in reattached fingers or limbs, although mechanisms underlying contractures or countermeasures to ameliorate them are not well understood. Here, using a rat femoral artery ischemia-reperfusion (I/R) model, we show that oxidative stress caused by accumulation of oxidative DNA damage occurs in gastrocnemius and soleus muscles after I/R induces muscle cell apoptosis. Moreover, we demonstrate that administration of the antioxidant N-acetyl cysteine (NAC) significantly suppresses oxidative stress accumulation and apoptosis induction in both muscles. We observed that collagen fibers accumulate in the gastrocnemius and soleus muscles after I/R in our model, and that collagen fiber accumulation was significantly suppressed by NAC administration. We demonstrate that adding hydrogen peroxide (H2O2), a reactive oxygen species (ROS), to an in vitro C2C12 myoblast culture system significantly increased expression of the apoptosis-inducing factors Bcl-2-associated X protein (BAX) and Caspase 3, while co-treatment with NAC significantly counteracted this increase and increased expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl2). Also using the C2C12 myoblast culture system, we show that H2O2 significantly increased expression of Cellular Communication Network Factor 2 (CCN2), which induces fibrosis, while co-addition of NAC with H2O2 significantly suppressed CCN2 induction. Our findings shed light on mechanisms underlying I/R injury in limbs and suggest countermeasures.},
}

Animals
*Apoptosis/drug effects
*Reperfusion Injury/metabolism/drug therapy/pathology
*Oxidative Stress/drug effects
*Acetylcysteine/pharmacology
Rats
*Collagen/metabolism
Male
*Hindlimb/pathology/metabolism/blood supply/drug effects
Muscle, Skeletal/metabolism/drug effects/pathology
Hydrogen Peroxide/pharmacology
Caspase 3/metabolism
bcl-2-Associated X Protein/metabolism
Rats, Sprague-Dawley
Reactive Oxygen Species/metabolism
Antioxidants/pharmacology

@article {pmid42715145,
year = {2026},
author = {Fu, X and Chang, J and Peng, S and Li, C and Xie, X and Qin, J and Li, J and Shang, G and Liu, H and Chen, W and Tian, S},
title = {Topical Vitamin C and N-Acetylcysteine for Reducing Symptoms After Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000001085},
pmid = {42715145},
issn = {2155-384X},
abstract = {BACKGROUND: Lugol chromoendoscopy improves detection of esophageal squamous neoplasia but can cause short-term retrosternal and pharyngeal discomfort. We evaluated topical vitamin C solution (VCS) and N-acetylcysteine (NAC) after Lugol staining.

METHODS: In this multicenter, randomized, double-blind, saline-controlled trial, 748 participants were allocated 1:1:1 to 0.9% normal saline (NS), 2% VCS, or 10% NAC after Lugol chromoendoscopy. The co-primary outcomes were overall post-procedure symptoms at 15 and 30 minutes. The main efficacy analysis was complete-case and included 681 participants; extreme-case analyses evaluated the effect of missing outcomes.

RESULTS: At 15 minutes, symptoms occurred in 44.34% of the NS group, 8.80% of the VCS group, and 9.43% of the NAC group. Relative risks versus NS were 0.198 (95% CI 0.126-0.312) for VCS and 0.213 (95% CI 0.140-0.322) for NAC. At 30 minutes, the corresponding incidences were 31.67%, 4.17%, and 4.10%, with relative risks of 0.132 (95% CI 0.067-0.257) and 0.129 (95% CI 0.068-0.245). Conclusions were unchanged in extreme-case sensitivity analyses. VAS category distributions favored both active-treatment groups. Median time to onset of decolorization was 11 seconds with NS and 2 seconds with each active solution; median time to complete decolorization was >180, 6, and 12 seconds, respectively.

CONCLUSIONS: Topical VCS and NAC each reduced short-term symptoms after Lugol chromoendoscopy compared with NS and promoted rapid mucosal decolorization. The direct comparison between VCS and NAC was exploratory and does not establish equivalence or non-inferiority.},
}

@article {pmid42695573,
year = {2026},
author = {Şahin, Y and Şahin, C and Kara, Ö},
title = {Nephroprotective Effects of Post-contrast N-Acetylcysteine and Montelukast Treatment in a Rat Model of Contrast-induced Acute Kidney Injury.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {235},
pages = {},
doi = {10.3791/73087},
pmid = {42695573},
issn = {1940-087X},
mesh = {Animals ; Sulfides ; Cyclopropanes ; *Acetates/administration & dosage/pharmacology/therapeutic use ; Male ; *Quinolines/administration & dosage/pharmacology/therapeutic use ; Rats ; *Acute Kidney Injury/chemically induced/prevention & control/drug therapy ; Rats, Wistar ; *Acetylcysteine/administration & dosage/therapeutic use/pharmacology ; *Contrast Media/adverse effects ; Disease Models, Animal ; Oxidative Stress/drug effects ; },
abstract = {Contrast-induced acute kidney injury (CI-AKI) is an important complication of iodinated contrast exposure in which oxidative stress and inflammatory processes contribute to renal damage. This study established an experimental rat model of CI-AKI and examined the effects of treatment initiated after contrast administration with N-acetylcysteine (NAC), montelukast, or a combination of both. Adult male Wistar rats underwent water deprivation followed by sequential intravenous administration of Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin, and iohexol. Treatment was initiated 1 h after completion of iohexol administration, approximately 1.5 h after L-NAME administration, and was continued once daily for 3 consecutive days. Renal function indices, oxidative stress parameters, inflammatory cytokines, renal injury biomarkers, and kidney histopathology were evaluated. The untreated CI-AKI group exhibited pronounced renal dysfunction, an unfavorable oxidative stress and inflammatory profile, and substantial histopathological damage. Compared with the untreated CI-AKI group, animals receiving NAC, montelukast, or the combined regimen generally showed improved biochemical and histopathological findings. Glutathione (GSH) levels were highest, and mean histopathological injury scores were numerically lowest in the combination group; however, combined treatment did not consistently outperform monotherapy across the assessed outcomes. This protocol provides a controlled preclinical framework for evaluating post-contrast interventions in CI-AKI, and the findings warrant further experimental investigation of NAC and montelukast without establishing clinical efficacy or a combination-specific advantage.},
}

Animals
Sulfides
Cyclopropanes
*Acetates/administration & dosage/pharmacology/therapeutic use
Male
*Quinolines/administration & dosage/pharmacology/therapeutic use
Rats
*Acute Kidney Injury/chemically induced/prevention & control/drug therapy
Rats, Wistar
*Acetylcysteine/administration & dosage/therapeutic use/pharmacology
*Contrast Media/adverse effects
Disease Models, Animal
Oxidative Stress/drug effects

@article {pmid42700943,
year = {2026},
author = {Ghosh, K},
title = {Therapeutic effect of curdlan in experimental visceral leishmaniasis is mediated by activation of NLRP3 inflammasome.},
journal = {Experimental parasitology},
volume = {289},
number = {},
pages = {109197},
doi = {10.1016/j.exppara.2026.109197},
pmid = {42700943},
issn = {1090-2449},
abstract = {Curdlan, a naturally occurring immunomodulator, significantly reduced the parasite load in experimental visceral through nitric oxide (NO) generation and interleukin 1β (IL-1β) production. Splenocyte supernatant from curdlan-treated mice infected with Leishmania donovani, when treated with anti-IL-1β antibody, showed a reduction in NO generation. Treatment with anti-IL-1β antibody to infected curdlan-treated mice reversed the protective effects against the infection. However, the underlying signaling events mediated by curdlan during infection remain to be elucidated. Curdlan strongly induced pro (inactive) form (signal 1) and then active form of IL-1β (signal 2) in parasite-infected macrophages, as revealed by immunoblot analysis. Given that caspase-1 is essential for the maturation of IL-1β from pro-IL-1β, we examined both forms of IL-1β in the presence of the caspase-1-specific inhibitor AcYVAD-Fmk in infected curdlan-treated cells. Notably, AcYVAD-Fmk treatment significantly inhibited the formation of active IL-1β following curdlan treatment, while the expression of pro-IL-1β remained unchanged. Curdlan significantly induced NLRP3 (nod-like receptor pyrin domain containing 3) inflammasome and adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), two critical regulators of IL-1β pathway in infected curdlan-treated cells. The gene silencing of NLRP3 in curdlan-treated infected cells failed to alter the pro-IL-1β expression. However, NLRP3 gene silencing inhibited IL-1β activation and parasite clearance, suggesting that a distinct second signal is necessary for maturation of IL-1β in the context of curdlan-mediated protection. Curdlan significantly increased the production of reactive oxygen species (ROS) and activated nuclear factor κB (NF-κB), two additional prerequisites for signal 1 and signal 2, respectively, in infected cells. Treatment of NF-κB inhibitor, BAY 11-7085 or ROS scavenger NAC (N-acetylcysteine) failed to release mature IL-1β and increased the parasite survival confirmed our observation. Our results suggest that curdlan-mediated curative effect may associate with the expression and activation of NLRP3 inflammasome resulting in the release of IL-1β secretion.},
}

@article {pmid42691115,
year = {2026},
author = {Stevenson, M and Wieczorek, R and Sticken, ET and Pour, SJ and Evenburg, T and Wu, T and Haberstroh, F and Otte, S and Simms, L and Chapman, F},
title = {Next generation nicotine product aerosol extracts exhibit reduced toxicological effects compared to cigarette smoke extracts in the ToxTracker Antioxidant and ToxProfiler MAX assays.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/geag033},
pmid = {42691115},
issn = {1464-3804},
abstract = {Smoking is a cause of serious diseases in adult smokers. Next generation products (NGP) can provide potentially reduced harm alternatives of nicotine delivery, due to the reductions in numbers and levels of toxicants associated with their use. These include heated tobacco and herbal products (HTPs/ HHPs) and electronic vapour products (EVPs). This study assessed the effects of a range of NGP (an HTP, an HHP and two EVPs) and a reference cigarette (1R6F) in the ToxTracker Antioxidant (AO) and ToxProfiler Mitotox Assessment Xtension (MAX) assays, which provide mechanistic insights via a range of cell stress endpoints. Aqueous extracts of smoke/ aerosol were generated by bubbling through phosphate-buffered saline solution, which was analysed for nicotine and carbonyl content. In the ToxTracker AO assay, 1R6F induced oxidative stress, genotoxicity and protein damage responses. Addition of N-acetyl cysteine (NAC) and glutathione (GSH) partially reduced selected responses, indicating oxidative stress contributes but does not fully account for all observed effects. Oxidative stress responses followed a similar trend for HTP; but was not classed as genotoxic. The HHP induced one oxidative stress marker, which was reduced by the addition of NAC/GSH. In the ToxProfiler MAX assay, 1R6F induced oxidative, endoplasmic reticulum and cell cycle stress. HTP induced the same stress pathways but was less potent than 1R6F. The HHP only induced an oxidative stress response, and at higher concentrations than 1R6F. The EVPs did not induce any of the cell stress markers across both assays and none of the test products induced mitochondrial toxicity. Overall, biological activity followed a decreasing gradient from 1R6F to HTP, HHP and EVPs. The findings of the assays used in this study reflect the proposed placement of such products on the relative reduced risk scale based on their smoke/aerosol chemistry and thus highlights the tobacco harm reduction potential of NGP.},
}

@article {pmid42691639,
year = {2026},
author = {Bai, P and Cao, X and Wang, S and Cao, Q and Li, T and Li, S and Liu, Y and Wu, B and Song, B},
title = {Diquat exposure disrupts ferroportin-dependent iron homeostasis and drives ferroptosis-associated white matter injury.},
journal = {Environment international},
volume = {215},
number = {},
pages = {110496},
doi = {10.1016/j.envint.2026.110496},
pmid = {42691639},
issn = {1873-6750},
abstract = {Diquat (DQ) is one of the most widely used bipyridyl herbicides and has been identified as a potential neurotoxin; however, its primary central nervous system (CNS) targets and the underlying mechanisms remain unclear. In cases of acute human DQ poisoning, subcortical white matter lesions have been reported to emerge approximately two weeks after exposure, with demyelination representing the predominant pathological finding. We used an acute oral DQ exposure rat model that mimics human DQ poisoning. Magnetic resonance imaging (MRI) revealed prominent white matter abnormalities in the corpus callosum, while histological analyses confirmed demyelination, impaired myelin integrity, reduced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, and marked mitochondrial ultrastructural damage. RNA sequencing indicated significant enrichment of ferroptosis-associated pathways. DQ induced sustained intracellular reactive oxygen species (ROS) accumulation and reduced nuclear factor erythroid 2-related factor 2 (Nrf2) expression. DQ exposure also reduced ferroportin (FPN) expression, accompanied by intracellular Fe[2][+] accumulation, enhanced lipid peroxidation, and ferroptotic cell death. In vivo, ferrostatin-1 pretreatment significantly attenuated DQ-induced demyelination. In vitro, N-acetylcysteine (NAC) partially restored Nrf2 expression and attenuated DQ-induced lipid peroxidation, whereas FPN overexpression reduced intracellular Fe[2][+] accumulation and lipid peroxidation. Collectively, these findings suggest that DQ disrupts redox balance and iron homeostasis in association with reduced Nrf2 signaling and FPN expression. Targeting FPN-mediated iron homeostasis warrants further investigation as a potential strategy for limiting DQ-induced neurotoxicity.},
}

@article {pmid42693967,
year = {2026},
author = {Yang, B and Song, Y and Wang, X and Zhang, L and Qin, Y},
title = {[Study on the mechanism of N-acetylcysteine in alleviating oxidative stress by inhibiting the mTOR/HIF-1α pathway in chronic obstructive pulmonary disease rats].},
journal = {Zhonghua wei zhong bing ji jiu yi xue},
volume = {38},
number = {8},
pages = {715-721},
doi = {10.3760/cma.j.cn121430-20260107-00016},
pmid = {42693967},
issn = {2095-4352},
mesh = {Animals ; *Oxidative Stress/drug effects ; *Pulmonary Disease, Chronic Obstructive/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Acetylcysteine/pharmacology ; Rats ; *TOR Serine-Threonine Kinases/metabolism ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Male ; Disease Models, Animal ; Lung/metabolism ; Malondialdehyde/metabolism ; },
abstract = {OBJECTIVE: To explore the mechanism by which N-acetylcysteine (NAC) regulates the mammalian target of rapamycin/hypoxia-inducible factor-1α (mTOR/HIF-1α) pathway to intervene in oxidative stress in rats with chronic obstructive pulmonary disease (COPD).

METHODS: Thirty-six SD rats were divided into the normal group, COPD model group and NAC treatment group by random number table method, with 12 rats in each group. The COPD rat model was established by cigarette smoke exposure combined with Klebsiella pneumoniae infection for 8 weeks. After the model was prepared, NAC was administered by oral gavage at a dose of 54 mg/kg once daily for 8 weeks. The normal group and the COPD model group were given the same amount of pure water by gavage. The effect of NAC on the pathological changes of lung tissue was observed by hematoxylin-eosin (HE) staining. The content of malondialdehyde (MDA) in serum and lung tissue was detected by the thiobarbituric acid method (TBA), the activity of total superoxide dismutase (T-SOD) in serum and lung tissue was detected by the hydroxylamine method, and the levels of lipid peroxide (LPO) and total antioxidant capacity (T-AOC) in serum and lung tissue were detected by colorimetry. Transcriptomic sequencing was used to analyze differentially expressed genes and predict the potential mechanism by which NAC inhibits oxidative stress in COPD. Molecular docking was used to observe the binding degree of NAC with the key proteins of the mTOR/HIF-1α pathway. Western blotting was used to detect the expression of proteins related to the mTOR/HIF-1α pathway in the lung tissue.

RESULTS: Compared with the normal group, the mean alveolar number (MAN) in lung tissue decreased, the mean linear intercept (MLI) increased, the levels of MDA and LPO in serum and lung tissue increased, the level of T-SOD in serum decreased, and the T-AOC in lung tissue decreased in the COPD model group. Compared with the COPD model group, NAC could improve lung tissue damage in COPD rats, and reduce the levels of MDA and LPO in serum and lung tissue [serum MDA (nmol/mg): 4.10±2.27 vs. 8.06±1.92, serum LPO (μmol/L): 1.88±0.59 vs. 2.88±0.82, lung tissue MDA (nmol/mg): 2.58±1.11 vs. 4.03±1.05, lung tissue LPO (μmol/L): 5.98±1.30 vs. 9.74±3.58, all P<0.05], increased T-SOD activity in serum (U/mg: 10.80±0.53 vs. 9.66±0.46, P<0.05). The results of transcriptomic analysis showed that the inhibition of antioxidant stress in COPD by NAC was related to the regulation of the HIF-1α pathway. The results of molecular docking showed that NAC had potential binding activity with mTOR, p70 ribosomal protein S6 kinase (p70S6K), and HIF-1α. The Western blotting data showed that NAC treatment could reduce the phosphorylation levels of mTOR at Ser2448 and p70S6K at Ser371 in the lung tissue of COPD model rats [p-mTOR/mTOR (relative expression level): 1.46±0.31 vs. 2.62±0.30, p-p70S6K/p70S6K (relative expression level): 2.15±0.25 vs. 3.80±0.73, both P<0.05], decreased the expression of HIF-1α [HIF-1α/GAPDH (relative expression level): 0.82±0.22 vs. 1.37±0.25, P<0.05].

CONCLUSIONS: NAC can alleviate oxidative stress in COPD rats by inhibiting the mTOR/HIF-1α pathway.},
}

Animals
*Oxidative Stress/drug effects
*Pulmonary Disease, Chronic Obstructive/metabolism
*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
*Acetylcysteine/pharmacology
Rats
*TOR Serine-Threonine Kinases/metabolism
Rats, Sprague-Dawley
Signal Transduction/drug effects
Male
Disease Models, Animal
Lung/metabolism
Malondialdehyde/metabolism

@article {pmid42684675,
year = {2026},
author = {Wei, S and Wang, F and Bai, B and An, Y and Sun, G},
title = {A machine learning-assisted colorimetric platform based on a Cu-doped carbon dot nanozyme for sensitive detection of N-acetylcysteine in serum.},
journal = {Analytical methods : advancing methods and applications},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6ay01708h},
pmid = {42684675},
issn = {1759-9679},
abstract = {N-Acetylcysteine (NAC), a thiol-containing mucolytic agent for COPD, exhibits significant pharmacokinetic variability among patients, motivating the need for convenient therapeutic monitoring. Herein, a colorimetric platform based on copper-doped chiral carbon dots (Cu-D-CDs) was synthesized via a one-pot hydrothermal route using D-histidine and CuCl2 as precursors. The Cu-D-CDs displayed enhanced peroxidase-like activity, catalyzing H2O2-mediated oxidation of TMB to blue oxTMB (λmax = 652 nm). Upon NAC introduction, oxTMB was reduced via a thiol-disulfide redox reaction, producing an absorbance decrease proportional to NAC concentration. Under optimized conditions, the assay exhibited a linear dynamic range of 10-90 µM, a detection limit of 3.74 µM (LOD = 3σ/S), and recoveries of 96.00-106.60% (RSD < 4%) in mouse serum, demonstrating its feasibility for NAC quantification in serum samples. Beyond the single-wavelength readout at 652 nm, the full-spectral data were further processed by an LSTM network, which significantly improved prediction accuracy (R[2] > 0.9998) compared with single-wavelength calibration (R[2] = 0.9979), effectively mitigating matrix interference. This integrated colorimetric-LSTM strategy shows promise for COPD therapeutic drug monitoring and pharmaceutical quality control.},
}

@article {pmid42688993,
year = {2026},
author = {Chang, X and Zhao, Y and Wang, Y and Shu, C and Feng, Y and Sun, Y and Zhu, G and Hou, J},
title = {N-acetylcysteine restores osteogenesis in human periodontal ligament stem cells by attenuating HIF-1α-driven oxidative stress and glycolytic reprogramming.},
journal = {Journal of dental sciences},
volume = {21},
number = {3},
pages = {1486-1498},
pmid = {42688993},
issn = {2213-8862},
abstract = {BACKGROUND/PURPOSE: Periodontitis-associated hypoxia signaling and oxidative stress severely impair the regenerative capacity of human periodontal ligament stem cells (hPDLSCs). This study investigated whether antioxidant intervention rescues hPDLSC osteogenesis under CoCl2-induced HIF-1α stabilization by modulating PI3K/Akt/HIF-1α/HO-1 signaling and glycolytic reprogramming.

MATERIALS AND METHODS: Primary hPDLSCs isolated from healthy premolars were characterized by flow cytometry and multilineage differentiation. To simulate periodontitis-associated stress, a CoCl2-induced HIF-1α-stabilizing condition was established. Cells were treated with the antioxidant N-acetylcysteine (NAC), the glycolysis inhibitor 2-deoxy-d-glucose (2-DG), or the PI3K inhibitor LY294002. Redox balance (DCFH-DA, MDA, GPX activity), glycolysis-related markers (HK2, GLUT1, lactate), and osteogenic-related markers (RUNX2, ALP, OCN) were quantified via qRT-PCR, Western blot, and biochemical assays, alongside an analysis of the PI3K/ Akt/HIF-1α/HO-1 signaling axis.

RESULTS: CoCl2 exposure triggered profound redox imbalance and significantly impaired hPDLSC osteogenesis. Crucially, NAC effectively reversed these damages and restored osteogenic capacity. Mechanistically, CoCl2-induced HIF-1α stabilization activated PI3K/Akt/HO-1 signaling, a pathological cascade attenuated by either NAC or targeted PI3K inhibition. Furthermore, CoCl2 forced a pronounced glycolytic shift characterized by upregulated HK2, GLUT1, and lactate production, which was directly intercepted by ROS clearance. Functionally, targeted glycolysis inhibition via 2-DG also successfully rescued the osteogenic potential of HIF-1α-stabilized hPDLSCs.

CONCLUSION: HIF-1α stabilization suppresses hPDLSC osteogenesis by inducing both oxidative stress and pathological glycolytic reprogramming. Targeted antioxidant intervention effectively mitigates these impairments, highlighting the ROS/PI3K/Akt/HIF-1α axis as a key link between redox imbalance and metabolic dysfunction, and suggesting a potential therapeutic target for periodontal regeneration.},
}

@article {pmid42683984,
year = {2026},
author = {Singh, K and Tyagi, S and Aggarwal, H},
title = {Modulation of mineralocorticoid receptor protects tributyltin chloride-induced early neurotoxic anomalies in rats.},
journal = {Indian journal of pharmacology},
volume = {58},
number = {5},
pages = {537-544},
pmid = {42683984},
issn = {1998-3751},
mesh = {Animals ; Male ; *Receptors, Mineralocorticoid/metabolism ; *Trialkyltin Compounds/toxicity ; Rats, Wistar ; Rats ; *Acetylcysteine/pharmacology/therapeutic use ; *Neurotoxicity Syndromes/prevention & control/metabolism/etiology ; Eplerenone ; Oxidative Stress/drug effects ; Behavior, Animal/drug effects ; *Mineralocorticoid Receptor Antagonists/pharmacology ; *Spironolactone/analogs & derivatives/pharmacology ; Blood-Brain Barrier/drug effects/metabolism ; Maze Learning/drug effects ; *Neuroprotective Agents/pharmacology ; },
abstract = {BACKGROUND: Tributyltin chloride (TBTC) is an organotin (OT) compound, a known neurotoxin and an endocrine disruptor, but it is inadequately characterized for its short-term exposure. This study aimed to explore the role of N-acetylcysteine (NAC) and Eplerenone in TBTC induced neurotoxicity in rats.

MATERIALS AND METHODS: Rats were exposed to a single dose of TBTC and were behaviorally assessed on open field test, light and dark box, Morris water maze, and rota rod test. Thiobarbituric acid reactive substances (TBARS) and nitrite were estimated as a measure of oxidative and nitrosative stress. Evans blue extravasation was used to assess the blood-brain barrier (BBB) integrity and morphological changes were assessed by histopathology. NAC (50 mg/kg) was used as a standard treatment, and eplerenone (50 and 100 mg/kg) was used as test interventions.

RESULTS: Short-term TBTC exposure produced significant anxiety-like behavioral alterations, accompanied by elevated brain TBARS and serum nitrite levels, indicating enhanced oxidative and nitrosative stress. BBB integrity was disrupted, and histopathological examination revealed early structural changes. Treatment with NAC and Eplerenone significantly attenuated behavioral disturbances, oxidative stress markers, BBB disruption, and histopathological damage. In contrast, no significant deficits were observed in spatial memory or motor coordination, likely due to the limited exposure duration.

CONCLUSION: TBTC induced early neurotoxic changes in the brain, which were attenuated by NAC and eplerenone administration. The beneficial effects support for further mechanistic studies on mineralocorticoid receptor modulation as a potential target for OT-induced neurotoxicity.},
}

Animals
Male
*Receptors, Mineralocorticoid/metabolism
*Trialkyltin Compounds/toxicity
Rats, Wistar
Rats
*Acetylcysteine/pharmacology/therapeutic use
*Neurotoxicity Syndromes/prevention & control/metabolism/etiology
Eplerenone
Oxidative Stress/drug effects
Behavior, Animal/drug effects
*Mineralocorticoid Receptor Antagonists/pharmacology
*Spironolactone/analogs & derivatives/pharmacology
Blood-Brain Barrier/drug effects/metabolism
Maze Learning/drug effects
*Neuroprotective Agents/pharmacology

@article {pmid42680044,
year = {2026},
author = {Kuo, YC and Huang, YC and Liu, YH and Chung, TW},
title = {Near-infrared-responsive silk/dopamine/fucoidan hydrogel incorporating multilayered silk-based nanoparticles as a reservoir for sequential and triggered NAC/NT delivery in diabetic wound healing.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {154316},
doi = {10.1016/j.ijbiomac.2026.154316},
pmid = {42680044},
issn = {1879-0003},
abstract = {Chronic diabetic wounds are characterized by excessive oxidative stress and impaired angiogenesis, presenting significant challenges for effective treatment. Herein, we developed a near-infrared (NIR)-responsive reservoir hydrogel (SD-NFA@SD/FC) capable of sustained and sequential drug delivery to promote diabetic wound healing. Free fucoidan (FC) was incorporated into a silk fibroin/dopamine (SD) hydrogel for early antioxidant and anti-inflammatory effects. Neurotensin (NT) and acetylcysteine (NAC) were sequentially assembled onto SD nanoparticles (224.61 ± 2.89 nm; zeta potential 1.36 ± 0.43 mV) via layer-by-layer (LbL) deposition and embedded within the hydrogel. The resulting system achieved sequential drug release, with rapid FC release within 24 h and sequentially sustained NAC and NT release for up to 10 days. Upon NIR triggering, NAC and NT showed enhanced release, increasing by approximately 10.6% and 15.0%, respectively, compared to the non-irradiated condition. In vitro, the hydrogel exhibited excellent biocompatibility and antioxidant activity while accelerating fibroblast migration to achieve complete wound closure within 12 h. In vivo, the NIR-triggered hydrogel markedly accelerated diabetic wound healing, achieving near-complete wound closure at day 14 with enhanced re-epithelialization, increased CD31[+] vessel density, and reduced CD68[+] macrophage infiltration. Accordingly, the NIR-responsive nanocomposite hydrogel represents a promising strategy for diabetic wound therapy.},
}

@article {pmid42682926,
year = {2026},
author = {Wang, S and Yang, X and Mcgowan, R and Hodge, B and Shan, D and Miller, N and Tang, J},
title = {RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.},
journal = {Experimental and therapeutic medicine},
volume = {32},
number = {4},
pages = {269},
pmid = {42682926},
issn = {1792-1015},
abstract = {Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD[+]/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.},
}

@article {pmid42671721,
year = {2026},
author = {Gou, W and Xie, Y and Xia, R and Gou, P and Cao, C and Luan, F and Liu, B and Li, Y},
title = {Intravenous Exposure to Amino-polystyrene Induces Excessive Autophagy and Apoptosis in Myocardium Through ROS Driven PI3K/AKT/mTOR Axis.},
journal = {Cardiovascular toxicology},
volume = {26},
number = {9},
pages = {},
pmid = {42671721},
issn = {1559-0259},
support = {YJJL2024034//Scientific Research Project of Yongchuan Hospital Affiliated to Chongqing Medical University/ ; },
mesh = {Animals ; *Reactive Oxygen Species/metabolism ; *Autophagy/drug effects ; *Polystyrenes/toxicity/administration & dosage/chemistry ; *TOR Serine-Threonine Kinases/metabolism ; *Apoptosis/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Myocytes, Cardiac/drug effects/pathology/enzymology ; Signal Transduction/drug effects ; Mice, Inbred BALB C ; Humans ; Cardiotoxicity ; *Phosphatidylinositol 3-Kinase/metabolism ; Cell Line ; Male ; Mice ; Injections, Intravenous ; Oxidative Stress/drug effects ; *Heart Diseases/chemically induced/pathology/enzymology ; },
abstract = {Polystyrene (PS) is a pervasive plastic whose threat to human health is growing, yet its cardiotoxicity, particularly under clinically relevant exposure scenarios, remains poorly understood. This study addresses this critical gap by modeling intravenous exposure to nanopolystyrene, simulating clinical situations where plastic-derived medical devices directly contact blood. We established an in vitro model using human AC16 cardiomyocytes and an in vivo model via tail vein injection in Balb/c mice to compare the effects of amino-modified (PS-NH2), carboxyl-modified (PS-COOH), and unmodified (PS-Bare) polystyrene nanoparticles. Our findings demonstrate that PS-NH2, in contrast to PS-COOH and PS-Bare, induces significant cardiotoxicity. This toxicity was initiated by a substantial increase in reactive oxygen species (ROS), which subsequently suppressed the PI3K/AKT/mTOR signaling axis. This inhibition led to the excessive activation of autophagy and the induction of apoptosis in cardiomyocytes. In vivo, PS-NH2 exposure caused severe pathological changes in mouse hearts, confirming its potent cardiotoxicity, characterized by inflammation, an impaired oxidative-antioxidant balance, and adverse cardiac remodeling. Notably, these detrimental effects were substantially reversed by the ROS scavenger N-acetylcysteine (NAC) or ginsenoside Rb1. In conclusion, our study reveals that Polystyrene positively charged amino-modified during degradation is the key to its cardiotoxicity, operating through a ROS-driven PI3K/AKT/mTOR pathway. These findings underscore the potential risks associated with specific surface modifications of nanoplastics and provide crucial insights for developing therapeutic strategies against plastic-induced cardiac injury.},
}

Animals
*Reactive Oxygen Species/metabolism
*Autophagy/drug effects
*Polystyrenes/toxicity/administration & dosage/chemistry
*TOR Serine-Threonine Kinases/metabolism
*Apoptosis/drug effects
*Proto-Oncogene Proteins c-akt/metabolism
*Myocytes, Cardiac/drug effects/pathology/enzymology
Signal Transduction/drug effects
Mice, Inbred BALB C
Humans
Cardiotoxicity
*Phosphatidylinositol 3-Kinase/metabolism
Cell Line
Male
Mice
Injections, Intravenous
Oxidative Stress/drug effects
*Heart Diseases/chemically induced/pathology/enzymology

@article {pmid42673752,
year = {2026},
author = {Song, D and Song, J and Hong, T and Lee, H and Bazer, FW and Song, G and Jeong, W and Lim, W},
title = {Tolylfluanid induces oxidative stress-associated calcium dysregulation and mitochondrial dysfunction in porcine trophectoderm and uterine luminal epithelial cells.},
journal = {Ecotoxicology and environmental safety},
volume = {323},
number = {},
pages = {120743},
doi = {10.1016/j.ecoenv.2026.120743},
pmid = {42673752},
issn = {1090-2414},
abstract = {Tolylfluanid is an aryl sulfamide fungicide widely used in agriculture and marine industries, but its effects on reproductive processes remain poorly understood. This study aimed to evaluate the cytotoxic effects of tolylfluanid and to investigate the mechanisms underlying its action via porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. These cells are essential for early embryonic development and implantation. Tolylfluanid reduced cell viability in monolayer cultures and impaired spheroid formation in 3D cultures, accompanied by cell-cycle dysregulation and apoptosis. It disrupted intracellular calcium homeostasis, causing mitochondrial calcium overload and cytosolic depletion, along with mitochondrial depolarization and reduced oxygen consumption and ATP production. At the molecular level, tolylfluanid reduced Bcl-xL levels while increasing BAK, cytochrome c, and cleaved caspase-3 levels, supporting the involvement of mitochondria-mediated apoptosis. MAPK and PI3K signaling pathways were also activated. Tolylfluanid also increased intracellular ROS levels and lipid peroxidation, accompanied by mitochondrial dysfunction, impaired migration, and signaling alterations. Co-treatment with N-acetylcysteine (NAC) prevented tolylfluanid-induced oxidative stress, mitochondrial dysfunction, calcium imbalance, and loss of cell viability. Collectively, these findings indicate that oxidative stress is an important contributor to the interconnected cellular alterations induced by tolylfluanid, which may affect cellular functions associated with early pregnancy.},
}

@article {pmid42673753,
year = {2026},
author = {Bai, L and Li, Y and Dong, L and Wang, Y and Yang, Y},
title = {ROS-mediated autophagy-apoptosis crosstalk regulates cell fate in the marine microalga Isochrysis galbana under BDE-47 stress.},
journal = {Ecotoxicology and environmental safety},
volume = {323},
number = {},
pages = {120740},
doi = {10.1016/j.ecoenv.2026.120740},
pmid = {42673753},
issn = {1090-2414},
abstract = {Although the regulatory crosstalk between autophagy and apoptosis in response to stress has been well documented in higher multicellular eukaryotes, its functional significance in marine microalgae exposed to persistent organic pollutants (POPs) remains largely unclear. Here, we investigated the coordinated responses of these two pathways in the marine microalga Isochrysis galbana exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a widespread coastal environmental contaminant. Exposure to BDE-47 (50-150 μg/L, 48 h) induced dose-dependent oxidative stress, characterized by excessive reactive oxygen species (ROS) accumulation, a decreased glutathione (GSH)/glutathione disulfide (GSSG) ratio, and increased malondialdehyde (MDA) content. Simultaneously, BDE-47 activated both the intrinsic apoptotic pathway, characterized by mitochondrial membrane potential (MMP) depolarization and elevated caspase-9 and caspase-3 activities, and the extrinsic pathway, reflected by the upregulation of Fas-associated death domain (FADD) and increased caspase-8 activity. Enhanced autophagic fluorescence intensity, autophagosomes formation, and upregulation of autophagy-related genes (ATGs) and proteins further confirmed that autophagy was also induced. Pharmacological inhibition assays revealed that the ROS scavenger N-acetylcysteine (NAC) markedly attenuated both autophagy and apoptosis, identifying ROS as a common upstream trigger for both processes. Inhibition of autophagy by 3-methyladenine (3-MA) exacerbated apoptotic damage, whereas blockade of apoptosis by Z-VAD-FMK promoted autophagic activity, indicating an antagonistic crosstalk in which autophagy suppresses apoptosis and vice versa. These findings demonstrate that the ROS-autophagy-apoptosis axis is functionally conserved in a marine microalga, and provide new insight into the cellular response of marine phytoplankton to organic pollutant stress.},
}

@article {pmid42662156,
year = {2026},
author = {Huang, F and Sun, K and Diao, L and Lu, K and Fan, Y and Xie, G},
title = {Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1928003},
pmid = {42662156},
issn = {1664-3224},
mesh = {Humans ; *Lupus Erythematosus, Systemic/immunology/genetics/therapy/drug therapy/etiology ; *DNA, Mitochondrial/genetics/immunology ; Biomarkers ; Animals ; cGAS-STING Signaling Pathway ; Toll-Like Receptor 9/metabolism ; *Mitochondria/genetics/metabolism/immunology ; Precision Medicine ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; },
abstract = {Mitochondrial DNA (mtDNA) is increasingly recognized as an active driver of immune dysregulation in systemic lupus erythematosus (SLE), yet most existing reviews treat it as a single damage signal rather than a multifunctional pathological mediator. This review presents an integrated framework examining mtDNA as a central hub linking mitochondrial dysfunction to systemic autoimmunity. We conducted a comprehensive synthesis of published evidence on mtDNA biology, its dysregulation in SLE, organ-specific injury mechanisms, and the clinical landscape of mtDNA-targeted therapeutic strategies. In SLE, intracellular mtDNA depletion coexists paradoxically with markedly elevated circulating cell-free mtDNA, a pattern correlating with disease activity and organ involvement. Sequential cytoplasmic and extracellular release of mtDNA engages cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), Toll-like receptor 9 (TLR9), and inflammasome platforms, establishing self-amplifying interferon and pro-inflammatory circuits that drive multi-organ pathology. We consolidate emerging evidence for mtDNA-related parameters as clinical biomarkers and propose a provisional patient stratification framework distinguishing two pathological subtypes with distinct therapeutic implications. Among current therapeutic strategies, N-acetylcysteine (NAC) and metformin carry the strongest clinical evidence, while cGAS-STING inhibitors and TLR9 antagonists represent compelling emerging candidates. mtDNA operates as an integrative pathological hub in SLE, and its dysregulation pattern carries both diagnostic and therapeutic significance. Incorporating mtDNA-based biomarkers into clinical monitoring and developing precision strategies targeting mtDNA-driven inflammatory circuits represent important steps toward individualized SLE management.},
}

Humans
*Lupus Erythematosus, Systemic/immunology/genetics/therapy/drug therapy/etiology
*DNA, Mitochondrial/genetics/immunology
Biomarkers
Animals
cGAS-STING Signaling Pathway
Toll-Like Receptor 9/metabolism
*Mitochondria/genetics/metabolism/immunology
Precision Medicine
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase

@article {pmid42666005,
year = {2026},
author = {Nabi, R and Faruqui, T and Khan, MS and Alafaleq, NO and Alvi, SS and Puri, P and Waiz, M and Yusuf, M and Ahmad, N and Khan, MS and Ahmad, S},
title = {N-Acetyl Cysteine Mitigates d-Ribose-Induced Protein Glycation and Aggregation Through Multiple Protective Mechanisms.},
journal = {IUBMB life},
volume = {78},
number = {9},
pages = {e70126},
pmid = {42666005},
issn = {1521-6551},
support = {ORF-2026-352//Deanship of Scientific Research, King Saud University/ ; },
mesh = {*Ribose/chemistry ; *Serum Albumin, Bovine/chemistry/metabolism ; *Acetylcysteine/pharmacology ; Glycosylation/drug effects ; *Glycation End Products, Advanced/metabolism/chemistry ; Animals ; Cattle ; *Protein Aggregates/drug effects ; Oxidative Stress/drug effects ; Antiglycation Agents ; Lysine/metabolism/chemistry ; Arginine ; Antioxidants/pharmacology ; },
abstract = {Advanced glycation end-products (AGEs) arise from non-enzymatic reactions between reducing sugars and proteins, contributing to oxidative stress and metabolic dysfunction. Excessive AGE accumulation is implicated in chronic diabetic complications and may also be relevant to acute metabolic disturbances encountered in emergency medicine. N-acetylcysteine (NAC), a naturally occurring antioxidant found in Allium species, has demonstrated potential to attenuate oxidative and glycation-mediated damage. The effect of NAC on d-ribose-induced glycation of bovine serum albumin (BSA) was investigated using multiple physicochemical and spectroscopic techniques. AGE formation was assessed by measuring hyperchromicity, early glycation products (ketoamines), carbonyl content, hydroxymethylfurfural (HMF) levels, and fluorescent AGEs. The protective effect of NAC was further evaluated by determining free lysine and arginine contents. Protein aggregation and conformational changes were analyzed using Congo Red binding and fluorescence assays including thioflavin-T and 1-anilinonaphthalene-8-sulfonic acid. NAC significantly inhibited d-ribose-mediated glycation of BSA in a concentration-dependent manner. Treatment with NAC resulted in reduced hyperchromicity, decreased ketoamine formation, and lower carbonyl, HMF, and fluorescent AGE levels. NAC preserved protein integrity by maintaining higher free lysine and arginine contents. In addition, NAC markedly attenuated glycation-induced protein aggregation, as evidenced by reduced Congo Red binding and diminished thioflavin-T and ANS fluorescence, with maximal protection observed at 300 μM. NAC exhibits pronounced anti-glycation and anti-aggregation effects by limiting oxidative stress and glycation-mediated protein modification. These findings demonstrate that NAC effectively attenuates d-ribose-induced glycation and protein aggregation in vitro and provide mechanistic insights into its anti-glycation properties through multiple complementary biochemical mechanisms. Further studies are warranted to evaluate its biological relevance in more complex experimental models.},
}

*Ribose/chemistry
*Serum Albumin, Bovine/chemistry/metabolism
*Acetylcysteine/pharmacology
Glycosylation/drug effects
*Glycation End Products, Advanced/metabolism/chemistry
Animals
Cattle
*Protein Aggregates/drug effects
Oxidative Stress/drug effects
Antiglycation Agents
Lysine/metabolism/chemistry
Arginine
Antioxidants/pharmacology

@article {pmid42670437,
year = {2026},
author = {Cheung, N},
title = {A Staged Translational Framework for Evaluating Oral Glutamatergic and Senescence-Modulating Strategies in Treatment-Resistant Depression.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {627814},
pmid = {42670437},
issn = {1177-8881},
mesh = {Humans ; Administration, Oral ; *Antidepressive Agents/administration & dosage/pharmacology/therapeutic use ; *Depressive Disorder, Treatment-Resistant/drug therapy/metabolism ; *Cellular Senescence/drug effects ; Animals ; Dextromethorphan/administration & dosage/pharmacology ; },
abstract = {Treatment-resistant depression (TRD) is commonly operationalized as non-remission after at least two adequately delivered antidepressant trials, but the biological heterogeneity of this population remains substantial. This article presents a translational hypothesis and drug-development framework; it reports no original clinical or laboratory data and is not a systematic review. The central hypothesis is that an oral dextromethorphan-CYP2D6-inhibitor-piracetam regimen could, if pharmacokinetically and clinically validated, initiate glutamatergic plasticity, whereas nicotinamide mononucleotide (NMN) plus N-acetylcysteine (NAC), followed only at a later stage by a candidate senescence-directed agent, could be evaluated for effects on the redox, bioenergetic, inflammatory, and cellular-aging context associated with response durability in a biomarker-enriched subset of unipolar TRD. The core regimen is defined as dextromethorphan, one prespecified CYP2D6 inhibitor, and piracetam. Glutamine is retained only as an optional exploratory component and is not part of the core or augmentation definition used for future testing. Existing evidence is uneven. Human studies establish that CYP2D6 phenotype and inhibition materially alter dextromethorphan exposure; NAC has heterogeneous adjunctive psychiatric evidence; NMN has human NAD-related target-engagement data without established antidepressant efficacy; and senolytics have limited early human data outside TRD. Dasatinib plus quercetin is therefore positioned as a later-stage, specialist-supervised research probe rather than a routine psychiatric augmentation. No clinical role can yet be assigned to any proposed combination, and none should be used outside formal research protocols. The proposed development sequence prioritizes pharmacokinetic characterization, safety, target engagement, biomarker-defined subgroup selection, controlled efficacy testing, and independent replication.},
}

Humans
Administration, Oral
*Antidepressive Agents/administration & dosage/pharmacology/therapeutic use
*Depressive Disorder, Treatment-Resistant/drug therapy/metabolism
*Cellular Senescence/drug effects
Animals
Dextromethorphan/administration & dosage/pharmacology

@article {pmid42656383,
year = {2026},
author = {Wu, Y and Qiao, X and Chen, S and Lu, Y and Mao, B and Zhu, M and Chen, X and Chen, N and Ding, Z and Jin, B},
title = {Protocatechualdehyde ameliorates OGD/R-induced endothelial injury via the ROS/miR-29b-3p/SIRT1 regulatory axis.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1904530},
pmid = {42656383},
issn = {1663-9812},
abstract = {INTRODUCTION: MicroRNA-29b-3p (miR-29b-3p) plays a critical role in regulating endothelial apoptosis and autophagy. We previously demonstrated that protocatechualdehyde (PCA), a water-soluble phenolic acid derived from Salvia miltiorrhiza Bge., protects human umbilical vein endothelial cells (HUVECs) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. However, whether miR-29b-3p mediates this protective effect remains unclear.

METHODS: Using the OGD/R in vitro model of ischemia-reperfusion injury, we investigated the molecular mechanisms underlying ischemic damage at the cellular level. RT-qPCR was used to measure miR-29b-3p expression, Western blotting to assess autophagy- and apoptosis-related proteins, and MDC staining and flow cytometry to evaluate autophagy and apoptosis, respectively.

RESULTS: The results showed that miR-29b-3p was downregulated in OGD/R-treated HUVECs, an effect that was reversed by PCA and the ROS inhibitor N-acetylcysteine (NAC). The miR-29b-3p mimic enhanced the promoting effects of PCA and NAC on miR-29b-3p expression, whereas miR-29b-3p inhibitor reversed these effects. Similarly, PCA-induced autophagy and inhibition of apoptosis were enhanced by the miR-29b-3p mimic and reversed by the inhibitor. To determine whether SIRT1 acts downstream of miR-29b-3p, we used EX527 (a SIRT1 inhibitor) and found that it attenuated the PCA-mediated upregulation of miR-29b-3p. The miR-29b-3p mimic enhanced PCA-induced SIRT1 activity and protein expression, while the inhibitor had the opposite effect. Additional experiments revealed that NAC suppressed ROS by upregulating miR-29b-3p, leading to increased SIRT1 expression and reduced apoptosis.

DISSCUSSION: Collectively, these findings demonstrate that PCA ameliorates OGD/R-induced endothelial injury by promoting autophagy and inhibiting apoptosis via the ROS/miR-29b-3p/SIRT1 regulatory axis.},
}

@article {pmid42651664,
year = {2026},
author = {Cugliari, A and Algieri, C and Glogowski, PA and Trombetti, F and Buscaroli, S and Fabbri, M and Federici, E and Nesci, S},
title = {Redox-Dependent Modulation of Cardiac Mitochondrial F1FO-ATPase and Respiratory Function by N-Acetylcysteine and Sodium Ascorbate.},
journal = {Biology},
volume = {15},
number = {16},
pages = {},
pmid = {42651664},
issn = {2079-7737},
support = {RFO 2025//University of Bologna/ ; },
abstract = {Oxidative stress is closely associated with mitochondrial dysfunction and contributes to the development of several human diseases. Among antioxidant compounds, ASC and NAC are widely used for their cytoprotective and redox-regulating properties; however, their direct effects on specific aspects of mitochondrial bioenergetics are only partially characterized. In the present study, we investigated the effects of ASC and NAC, individually and combined, on Mg[2+]-dependent F1FO-ATPase hydrolysis, mitochondrial free thiol content and respiration in isolated swine heart mitochondria. ASC significantly stimulated F1FO-ATPase activity in a concentration-dependent manner, whereas kinetic analysis indicated a mixed uncompetitive activation mechanism. In contrast, NAC alone did not significantly affect F1FO-ATPase activity but abolished the stimulatory effect of ASC when the two compounds were combined. Both ASC and NAC increased mitochondrial free thiol content, although no change was observed under combined treatment conditions. Mitochondrial oxygen consumption analysis revealed substrate-dependent effects of the two antioxidants on electron transport. Overall, ASC and NAC exerted distinct direct actions on isolated mitochondria, and their combination did not produce additive or synergistic effects. These findings provide new insights into the direct modulation of mitochondrial function by antioxidant compounds and may contribute to expanding understanding of their potential therapeutic and dietary supplement applications, particularly when combined.},
}

@article {pmid42653151,
year = {2026},
author = {Kouki, A and Bouzazi, D and Trabelsi, A and Mbirki, L and Bouadballah, S and El-Bok, S and Beyrem, H and Valerii, MC and Spisni, E and Aouani, E and Ben-Attia, M},
title = {N-Acetylcysteine, Tiron, and Their Combination: In Vitro Antioxidant and Anti-Inflammatory Activities and Their Protective Effect in a Rat Model of Acetic Acid-Induced Ulcerative Colitis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
pmid = {42653151},
issn = {1422-0067},
support = {//University of Bologna/ ; },
mesh = {Animals ; *Acetylcysteine/pharmacology/therapeutic use/chemistry ; *Colitis, Ulcerative/drug therapy/chemically induced/pathology/metabolism ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Antioxidants/pharmacology/chemistry/therapeutic use ; Rats ; Acetic Acid/toxicity/adverse effects ; Male ; Rats, Wistar ; Disease Models, Animal ; *1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology/therapeutic use/chemistry ; Oxidative Stress/drug effects ; Drug Therapy, Combination ; },
abstract = {Ulcerative colitis is characterized by inflammation, oxidative stress, and excessive free radical production. This study investigated the antioxidant, anti-inflammatory, and protective effects of N-acetylcysteine (NAC), Tiron, and their fixed-ratio combination in acetic acid-induced colitis. An integrated approach was used, combining ligand-ligand docking, acellular antioxidant and protein-denaturation assays, and an in vivo model in male Wistar rats. Colitis was induced by intrarectal administration of 3% acetic acid after 14 days of intraperitoneal pretreatment with NAC, Tiron, or NAC-Tiron. Docking analysis suggested physicochemical compatibility through non-covalent interactions. In vitro, NAC, Tiron, and their combination showed antioxidant and anti-denaturation activities. NAC-Tiron displayed greater activity than the individual compounds in selected endpoints, particularly 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, but did not consistently outperform them across the other assays. In vivo, NAC, Tiron, and NAC-Tiron attenuated macroscopic and histological colonic damage, reduced inflammatory cell infiltration and edema, decreased lipid peroxidation and protein carbonylation, and helped preserve superoxide dismutase (SOD) activity, reduced glutathione (GSH), and total thiols. The treatments also attenuated increases in C-reactive protein (CRP) and free iron without evident worsening of the measured systemic biochemical parameters. Overall, these findings provide an exploratory proof of concept for fixed-ratio NAC-Tiron co-administration but do not establish pharmacological synergy or superiority over standard therapies.},
}

Animals
*Acetylcysteine/pharmacology/therapeutic use/chemistry
*Colitis, Ulcerative/drug therapy/chemically induced/pathology/metabolism
*Anti-Inflammatory Agents/pharmacology/therapeutic use
*Antioxidants/pharmacology/chemistry/therapeutic use
Rats
Acetic Acid/toxicity/adverse effects
Male
Rats, Wistar
Disease Models, Animal
*1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology/therapeutic use/chemistry
Oxidative Stress/drug effects
Drug Therapy, Combination

@article {pmid42654153,
year = {2026},
author = {Zhang, Y and Guo, J and Qiu, H and Liu, J and Zhang, C and Zhou, L and Wang, C and Li, L and Hou, X},
title = {N-Acetylcysteine-Functionalized Mixed Micelles Overcome Multiple Intestinal Barriers to Improve Oral Bioavailability and Antioxidant Protection of Imperatorin.},
journal = {Pharmaceutics},
volume = {18},
number = {8},
pages = {},
pmid = {42654153},
issn = {1999-4923},
support = {2024KFKT05//Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application/ ; 2023SYKFD08//Anhui Engineering Technology Research Center of Biochemical Pharmaceutical/ ; YZJ2026005//Anhui Innovative Center for Drug Basic Research of Metabolic Diseases/ ; 2022AH051226, 2022AH051231//Key Project of the Natural Science Foundation of the Department of Education of Anhui Province/ ; 2024yjsxxsfkc044//Anhui Province New Era Education Quality Project/ ; S202510368002//College Students' Innovative Entrepreneurial Training Plan Program/ ; },
abstract = {Background: Imperatorin (IPT) is a natural furanocoumarin featuring robust anti-inflammatory, antifibrotic and antioxidant activities. However, poor aqueous solubility and insufficient oral bioavailability restrict its clinical application. Multiple gastrointestinal barriers, including the mucus barrier, limited epithelial penetration and P-glycoprotein-triggered drug efflux, are major obstacles hindering IPT oral absorption. Methods: N-acetylcysteine (NAC)-functionalized TPGS conjugates were synthesized first. Using Pluronic[®] F108 and Lipoid[®] S-100 as a matrix, imperatorin@N-acetylcysteine-TPGS/Pluronic[®] F108/Lipoid[®] S-100 (IPT@NAC-TFS) micelles were fabricated. We characterized their physicochemical features and in vitro release behavior. The Caco-2/HT29-MTX-E12 co-culture cell model was adopted to explore mucus permeation, cellular uptake and transepithelial transport mechanisms. In vivo intestinal distribution and pharmacokinetic tests in rats were carried out to confirm the oral absorption-enhancing effect of micelles. Results: Optimized micelles displayed a uniform shape and favorable encapsulation efficiency. Low CMC maintained structural stability upon gastrointestinal dilution. NAC modification conferred mucus-penetrating capacity on micelles. TPGS simultaneously improved epithelial barrier permeability and inhibited drug efflux, switching IPT transport mode. The micelles effectively cleared intracellular ROS, recovered SOD activity and lowered MDA levels in BLM-impaired MLg fibroblasts. In vivo results revealed enhanced intestinal drug accumulation, with the relative oral bioavailability of IPT increased by 6.07-fold. Conclusions: IPT@NAC-TFS micelles overcome multiple gastrointestinal barriers for oral IPT delivery. Combining mucus penetration, efflux suppression and antioxidative capacity, this system offers a promising strategy to develop oral formulations of poorly soluble antifibrotic natural products.},
}

@article {pmid42654847,
year = {2026},
author = {Chen, S and Chen, W and Li, X and Zhou, W and Sun, R and Zhou, L and Zhang, Y and Zhao, Q},
title = {Exogenous N-Acetyl-L-cysteine Improves Soybean Saline-Alkali Tolerance by Enhancing the hGSH Pathway to Alleviate Oxidative Damage.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {16},
pages = {},
pmid = {42654847},
issn = {2223-7747},
support = {2023YFD2300103-03//National Key Research and Development Program of China/ ; CARS-04-01A//China Agriculture Research System/ ; YJSCX2025-Z02//Graduate Innovation Training Program/ ; },
abstract = {Soil salinization and alkalization severely threaten global agricultural sustainability. Although N-acetylcysteine (NAC) is well known as an antioxidant in animal research, its effects on plant salt-alkali tolerance and the underlying mechanisms remain unclear. This study investigated the regulatory effects of foliar-sprayed NAC on two soybean (Glycine max) cultivars-salt-tolerant HF50 and salt-sensitive HN95-under saline-alkali stress. Exogenous NAC alleviated seedling growth inhibition by supplying cysteine, which elevated glutamate-cysteine ligase (GCL) activity and promoted homoglutathione (hGSH) accumulation. It further strengthened the ascorbic acid (AsA)-glutathione/homoglutathione ((h)GSH) cycle and elevated antioxidant enzyme activities, thereby relieving oxidative injury, while also activating DNA repair pathways to preserve genomic stability and protecting chloroplast and mitochondrial integrity. Notably, distinct genotype- and tissue-specific responses to NAC were detected. HN95 relied primarily on root antioxidant defenses in a strongly concentration-dependent manner, whereas HF50 coordinated antioxidant metabolism and DNA repair more effectively, showing consistent responses to NAC concentrations. These findings elucidate the coordinated physiological and molecular mechanisms by which exogenous NAC mitigates saline-alkali damage in soybean, providing a theoretical foundation for using NAC to enhance crop stress resilience and develop sustainable cultivation techniques for saline-alkali soils.},
}

@article {pmid42651088,
year = {2026},
author = {Romero-Sánchez, HA and Ríos, C and Martínez-Cárdenas, MLÁ and Navarro, L and Moreno-Rocha, LA and Mata-Bermudez, A and Díaz-Ruiz, A},
title = {Dapsone and N-Acetylcysteine Exert a Synergistic Antinociceptive Effect Associated with Oxidative Stress After Traumatic Spinal Cord Injury: An Isobolographic Study.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
pmid = {42651088},
issn = {2076-3425},
support = {1143882//The Secretary of Science, Humanities, Technology and Innovation (SECIHTI)/ ; },
abstract = {Background/Objectives: Neuropathic pain (NP) after traumatic spinal cord injury (SCI) is highly prevalent, markedly impairs quality of life, and remains difficult to treat because available therapies show limited efficacy and may cause relevant adverse effects. Because oxidative stress and glutamate-mediated excitotoxicity contribute to central sensitization after SCI, this study evaluated the antinociceptive and antioxidant effects of dapsone (DDS), N-acetylcysteine (NAC), and their combination in rats with SCI. An isobolographic analysis was also performed to determine the pharmacodynamic interaction between the two drugs. Methods: Female Wistar rats with SCI that developed stimulus-dependent hypersensitivity from day 15 after injury were treated once daily for 7 days with DDS (1.5-12.5 mg/kg, i.p.), NAC (9.3-75 mg/kg, i.p.), or 1:1 fixed-ratio combinations. Mechanical allodynia and hyperalgesia were assessed with Von Frey filaments, whereas lipid peroxidation (LP) and reduced glutathione (GSH) were quantified in injured spinal cord tissue. Results: DDS and NAC produced dose-dependent antinociceptive effects, with DDS being more potent than NAC in both endpoints. The individual ED50 values were 4.92 and 33.47 mg/kg for allodynia, and 4.06 and 27.74 mg/kg for hyperalgesia, for DDS and NAC, respectively. The DDS/NAC combination showed synergistic interactions in allodynia (ED50 = 7.45 mg/kg vs. Zadd = 19.19 mg/kg; γ = 0.388) and hyperalgesia (ED50 = 4.21 mg/kg vs. Zadd = 15.90 mg/kg; γ = 0.265), with stronger synergism in hyperalgesia. Combined treatment also improved LP and GSH levels. Conclusions: These findings indicate that DDS and NAC exert complementary actions and that their combination produces a synergistic antinociceptive effect associated with diminished oxidative stress after SCI.},
}

@article {pmid42650296,
year = {2026},
author = {Oberacker, T and Leibold, T and Salega, A and Kraft, L and Schanz, M and Ketteler, M and Latus, J and Schricker, S},
title = {N-Acetylcysteine Protects HPMCs from High-Glucose-Induced Oxidative DNA Damage.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {42650296},
issn = {2076-3921},
support = {//Berthold-Leibinger Foundation/ ; },
abstract = {Peritoneal dialysis (PD) is an effective renal replacement therapy; however, its long-term use is limited by the detrimental effects of glucose-based PD fluids on the peritoneal membrane, contributing to fibrosis and ultrafiltration failure. Previous studies have demonstrated that high-glucose exposure promotes oxidative DNA damage through upregulation of thioredoxin-interacting protein (TXNIP) expression, resulting in reduced thioredoxin (Trx) activity. This study investigated strategies to reduce oxidative stress in human peritoneal mesothelial cells exposed to high glucose concentrations. TXNIP expression, Trx activity, intracellular oxidative stress levels, and oxidative DNA damage were analyzed. High-glucose exposure caused a dose-dependent increase in TXNIP expression, a 5-15% reduction in Trx activity, and increased intracellular oxidative stress levels and oxidative DNA damage. Pre-treatment with the ROS scavenger N-acetylcysteine (NAC) reduced these effects. These findings demonstrate that glucose-induced TXNIP upregulation disrupts cellular redox homeostasis, resulting in increased intracellular oxidative stress and oxidative damage. Antioxidant compounds may therefore represent promising therapeutic strategies to protect the peritoneal membrane and improve long-term outcomes in PD.},
}

@article {pmid42627401,
year = {2026},
author = {Kim, TH and Cho, KJ and Hwang, HH and Lee, HC and Ko, SG},
title = {JI-CS004, a chloroform fraction of SH003, induces reactive oxygen species-dependent intrinsic apoptosis via endoplasmic reticulum stress-associated mitochondrial dysfunction in human colorectal cancer cells.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42627401},
issn = {1573-4978},
support = {RS-2020-NR049559//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Endoplasmic Reticulum Stress/drug effects ; *Apoptosis/drug effects ; *Colorectal Neoplasms/metabolism/drug therapy/pathology ; *Mitochondria/drug effects/metabolism ; Animals ; Chloroform/pharmacology/chemistry ; Mice ; Cell Line, Tumor ; Signal Transduction/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Xenograft Model Antitumor Assays ; HCT116 Cells ; Cell Survival/drug effects ; Mice, Nude ; Plant Extracts/pharmacology ; },
abstract = {UNLABELLED: Conventional therapies for colorectal cancer (CRC) are often limited by toxicity and therapeutic resistance. Alternative therapeutic strategies are therefore needed. Natural product-derived compounds have been explored as potential anticancer agents. The molecular mechanisms underlying the anticancer effects of JI-CS004, a chloroform fraction derived from the herbal formulation SH003, against CRC remain unclear.

METHODS: The anticancer effects of JI-CS004 were evaluated in CRC cell lines by assessing reactive oxygen species (ROS) generation, ER stress signaling, mitochondrial dysfunction, and intrinsic apoptosis. ROS dependency was examined using N-acetylcysteine (NAC). Antitumor activity was evaluated in an HCT116 xenograft model.

RESULTS: JI-CS004 substantially reduced CRC cell viability and induced intracellular ROS accumulation. ROS scavenging by NAC markedly attenuated JI-CS004-induced cytotoxicity, ER stress signaling, mitochondrial dysfunction, and intrinsic apoptosis, supporting an important contribution of ROS to these cellular responses. JI-CS004 activated ER stress-related signaling through the PERK/eIF2α/ATF4 and IRE1α/JNK pathways, increased CHOP expression, reduced mitochondrial membrane potential and OXPHOS complex expression, and induced intrinsic apoptosis accompanied by cytochrome c release and caspase-9/3 activation. In vivo, JI-CS004 substantially suppressed tumor growth and increased the expression of CHOP and cleaved caspase-3.

CONCLUSIONS: JI-CS004 induces ROS-dependent intrinsic apoptosis associated with ER stress and mitochondrial dysfunction, supporting further investigation of its anticancer potential in CRC.},
}

Humans
*Reactive Oxygen Species/metabolism
*Endoplasmic Reticulum Stress/drug effects
*Apoptosis/drug effects
*Colorectal Neoplasms/metabolism/drug therapy/pathology
*Mitochondria/drug effects/metabolism
Animals
Chloroform/pharmacology/chemistry
Mice
Cell Line, Tumor
Signal Transduction/drug effects
Membrane Potential, Mitochondrial/drug effects
Xenograft Model Antitumor Assays
HCT116 Cells
Cell Survival/drug effects
Mice, Nude
Plant Extracts/pharmacology

@article {pmid42628363,
year = {2026},
author = {Lee, SJ and Lee, JY},
title = {Isoprothiolane disrupts mitochondrial and endoplasmic reticulum homeostasis and impairs development of the embryonic nervous system in zebrafish.},
journal = {Journal of hazardous materials},
volume = {516},
number = {},
pages = {143335},
doi = {10.1016/j.jhazmat.2026.143335},
pmid = {42628363},
issn = {1873-3336},
abstract = {Isoprothiolane (IPT) is a widely used fungicide in Asian rice cultivation, yet its toxicological profile remains incompletely characterized, particularly regarding dermal exposure relevant to occupational settings. This study evaluated the cytotoxic mechanisms and developmental consequences of IPT exposure using human keratinocytes (HaCaT), dermal fibroblasts (HDF), and zebrafish (Danio rerio) embryos. In human skin cells, IPT produced predominantly cytostatic effects associated with severe mitochondrial dysfunction, including membrane depolarization, impaired oxidative phosphorylation, and a near-complete loss of spare respiratory capacity. IPT also induced an ER stress-associated response, evidenced by increased BiP expression, eIF2α phosphorylation, and concentration-dependent induction of ATF4 and CHOP. In zebrafish embryos, IPT exposure resulted in concentration-dependent developmental toxicity characterized by pericardial edema, reduced heart rate, growth retardation, and defects in eye and brain development. Toxicological assessments demonstrated pronounced ROS accumulation and increased apoptosis signals in cranial and retinal regions, accompanied by disrupted angiogenesis and neural development. N-acetylcysteine (NAC) attenuated ROS accumulation and vascular and neural abnormalities, supporting a contributory role of oxidative stress in these developmental effects. Collectively, these findings reveal sublethal mitochondrial bioenergetic impairment and ER stress-associated responses in human skin-derived cells, together with oxidative stress-associated vascular and neural developmental abnormalities in zebrafish, providing a broader understanding of IPT toxicity.},
}

@article {pmid42628723,
year = {2026},
author = {Gagliardi, CF and de Castro Santos, A and Warner, K and Garakis, MCV and Nor, J and Cavalcanti, B},
title = {N-acetyl cysteine as an adjuvant medication for regenerative endodontics.},
journal = {Journal of endodontics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.joen.2026.08.018},
pmid = {42628723},
issn = {1878-3554},
abstract = {OBJECTIVE: To perform an in vitro evaluation of the effects of N-acetyl cysteine (NAC) on the viability and osteogenic expression of dental pulp stem cells (DPSC), as well as its mechanical removability from root canals.

METHODS: DPSC were exposed to NAC at concentrations of 0.01, 0.1, and 1 mg/mL under stabilized and non-stabilized pH conditions for 24 or 48 hours. Cell viability was assessed using the sulforhodamine-B (SRB) assay. Osteocalcin (OCN) expression, with or without induction of oxidative stress (H2O2), was quantified by ELISA. NAC removal was evaluated in bovine teeth by scanning electron microscopy (SEM) after using three irrigation techniques: conventional irrigation (CI), EasyClean (EC), and passive ultrasonic irrigation (PUI). Data was analyzed by two-way ANOVA (p<0.05).

RESULTS: After 24 hours, NAC did not show cytotoxic effects at any concentration or pH condition. At 48 hours, a significant reduction in viability was observed at 0.1 and 1 mg/mL NAC (p<0.05), while 0.01 mg/mL NAC maintained viability similar to the control. OCN was expressed in all groups but statistically reduced in the presence of Reactive Oxygen Species (ROS). SEM analysis showed no statistical differences between the groups or among root thirds (p>0.05).

CONCLUSION: NAC showed low cytotoxicity at short exposure times, especially at 0.01 mg/mL, and recovery of OCN expression. Its removal was feasible regardless of the irrigation technique or root third evaluated. The results provide relevant evidence regarding the safety, cellular behavior, and removal of NAC from the canal walls.},
}

@article {pmid42628901,
year = {2026},
author = {Liu, M and Cao, X and Li, S and Guo, Y and Li, X and Li, J},
title = {ROS-driven crosstalk between ferroptosis and necroptosis mediates neurotoxicity induced by maternal exposure to polystyrene nanoplastics in zebrafish.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {409},
number = {},
pages = {129001},
doi = {10.1016/j.envpol.2026.129001},
pmid = {42628901},
issn = {1873-6424},
abstract = {The pervasive environmental distribution of nanoplastics (NPs) raises critical concerns regarding their offspring health impacts. However, the precise mechanisms underlying neurotoxicity induced by maternal exposure to NPs remain poorly understood. In this study, adult female zebrafish were exposed to polystyrene nanoplastics (PS-NPs; 0.1 and 1 mg/L) for 28 days to investigate maternal transfer, subsequent neurotoxic effects, and associated cell death pathways in offspring. Fluorescence imaging confirmed the concentration-dependent accumulation of maternally transferred PS-NPs in embryos and larvae. Consequently, maternal exposure to PS-NPs significantly reduced fertilization and hatching rates, increased malformation incidence, and impaired larval development. Behavioral analyses revealed decreased locomotor activity and impaired light-dark responsiveness, accompanied by structural neuronal disorganization and reduced neuronal density in the telencephalon. Transcriptomic and molecular analyses indicated that maternal exposure to PS-NPs severely disrupted iron homeostasis characterized by iron overload and excessive reactive oxygen species (ROS) burst, and lipid peroxidation, which concurrently altered the expression of critical genes related to ferroptosis and necroptosis. Antioxidant intervention using N-acetylcysteine (NAC) effectively alleviated oxidative stress and rescued alterations in ferroptosis and necroptosis, while ferrostatin-1 (Fer-1) improved iron homeostasis, attenuated neuronal injury, and mitigated necroptosis-related responses. Collectively, our findings suggest that ROS-associated ferroptosis and necroptosis contribute to offspring neurotoxicity induced by maternal exposure to PS-NPs and indicate a potential functional crosstalk between these two regulated cell death pathways. This study provides new insights into the mechanisms underlying offspring neurotoxicity induced by NPs.},
}

@article {pmid42629950,
year = {2026},
author = {Ahmed, K and Muneer, R and Tayyab, H and Memon, AS and Damji, KF and Khan, I},
title = {Cytoprotective Potential of N-Acetylcysteine in an In Vitro Model of Retinal Oxidative Injury.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261480480},
doi = {10.1177/10807683261480480},
pmid = {42629950},
issn = {1557-7732},
abstract = {PURPOSE: Sodium iodate (NaIO3) is a well-established oxidizing agent that induces oxidative stress (OS) in ARPE-19 cells, while antioxidants such as N-acetylcysteine (NAC) have demonstrated cytoprotective effects in retinal degeneration models. This study establishes an in vitro NaIO3-induced OS disease model to investigate pathways involved in RPE damage and restoration, providing a platform for preclinical screening of antioxidant molecules.

METHODS: The cytoprotective effect of NAC on NaIO3-induced OS in RPE cells was evaluated using CMFDA cell viability assay (2',7'-dichlorofluorescin diacetate), JC-1 staining, colony-forming unit assay, scratch assay, PI/Annexin V staining, and gene expression analysis related to OS, inflammation, the cell cycle, and autophagy.

RESULTS: NAC treatment significantly decreased ROS levels and stabilized mitochondrial potential, increased cell viability and colony-forming ability, cell adhesion and migration potential. Furthermore, NAC prevented NaIO3-induced cell death and modulated the expression of genes associated with OS, inflammation, cell cycle, and autophagy.

CONCLUSION: The results showed successful establishment of a reproducible OS-based retinal degeneration model in ARPE-19 cells. Additionally, NAC exhibited significant cytoprotective activity against OS in RPE cells, highlighting its therapeutic potential as an antioxidant agent against retinal degeneration by reducing ROS levels, restoring mitochondrial membrane potential, and attenuating cell cycle dysregulation and inflammation.},
}

@article {pmid42638853,
year = {2026},
author = {Jiao, Y and Jia, Q and Zhang, X and Zhang, C and Wei, C and Wang, D and Liu, X and Li, H and Hu, A and Zeng, L and Li, L and Yao, P},
title = {Early-life oxidative stress programs persistent NFκB activation and neuroinflammation in autism spectrum disorder.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1869130},
pmid = {42638853},
issn = {1664-3224},
mesh = {Animals ; *Oxidative Stress ; *NF-kappa B/metabolism ; *Autism Spectrum Disorder/metabolism/immunology/etiology ; Humans ; Mice ; Female ; *Neuroinflammatory Diseases/metabolism/etiology ; Male ; Signal Transduction ; Pregnancy ; Prenatal Exposure Delayed Effects/metabolism ; Disease Models, Animal ; Valproic Acid ; Child ; Antioxidants/pharmacology ; },
abstract = {BACKGROUND: Oxidative stress and immune dysregulation are hallmark features of autism spectrum disorder (ASD), yet whether oxidative imbalance acts as an upstream trigger of immune activation remains unclear. The redox-sensitive transcription factor NFκB represents a potential mechanistic link. We investigated whether early-life oxidative stress contributes to persistent NFκB activation and neuroinflammation in ASD.

METHODS: Umbilical cord blood and peripheral blood from ASD and typically developing children were analyzed for redox markers (GSH/GSSG ratio, malondialdehyde, 8-oxo-dG), NFκB activation (p65 DNA-binding and nuclear translocation), and inflammatory gene expression. The mechanistic relationship between oxidative stress and NFκB signaling was investigated in prenatal valproic acid (VPA)-exposed mice using antioxidant intervention (N-acetylcysteine, NAC), NFκB inhibition (Bay 11-7082), pro-oxidant challenge, behavioral assays, and primary amygdala neuron models.

RESULTS: ASD children exhibited persistent oxidative imbalance detectable at birth, accompanied by increased NFκB activation and pro-inflammatory gene expression. VPA-exposed mice recapitulated these molecular and behavioral abnormalities. In primary neurons, oxidative stress directly enhanced NFκB activity and promoter binding, whereas antioxidant and mitochondrial-targeted approaches suppressed NFκB activation. Developmentally, oxidative stress preceded sustained NFκB activation, and prenatal, but not postnatal, NAC treatment prevented these abnormalities. NAC restored redox homeostasis, reduced NFκB signaling, and improved behavioral deficits, whereas NFκB inhibition alone attenuated inflammatory responses but failed to correct oxidative imbalance or behavioral abnormalities.

CONCLUSION: Early-life oxidative stress is an upstream pathogenic event associated with persistent NFκB activation and neuroinflammation in ASD. NFκB primarily mediates inflammatory signaling, while oxidative stress likely contributes to ASD-related behaviors through additional downstream pathways. These findings highlight early redox modulation as a potential therapeutic strategy.},
}

Animals
*Oxidative Stress
*NF-kappa B/metabolism
*Autism Spectrum Disorder/metabolism/immunology/etiology
Humans
Mice
Female
*Neuroinflammatory Diseases/metabolism/etiology
Male
Signal Transduction
Pregnancy
Prenatal Exposure Delayed Effects/metabolism
Disease Models, Animal
Valproic Acid
Child
Antioxidants/pharmacology

@article {pmid42644995,
year = {2026},
author = {Junckes, ES and Munzlinger, PE and Dalmolin, C and Fosca, M and Meier, MM and Rau, JV},
title = {N-Acetylcysteine Applied to Hydrogels: A Comprehensive Systematic Review.},
journal = {Gels (Basel, Switzerland)},
volume = {12},
number = {8},
pages = {},
pmid = {42644995},
issn = {2310-2861},
support = {Finance Code 001//Coordenação de Aper-feiçoamento de Pessoal de Nível Superior - Brasil (CAPES)/ ; Grant No. 2025TR001425//Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina/ ; Edital PDSE UDESC 01/2024//Programa Doutorado Sanduíche no Exterior/ ; },
abstract = {N-acetylcysteine (NAC) is a thiol-containing molecule with antioxidant, anti-inflammatory, antimicrobial, and cytoprotective properties that has increasingly been incorporated into hydrogel-based biomaterials. This systematic review evaluates the strategies used to integrate NAC into hydrogels and examines their effects on material properties, controlled release, biocompatibility, and therapeutic activity. The review was conducted according to the PRISMA guidelines using Scopus, PubMed, Web of Science, and SciFinder to identify English-language articles published between 2000 and 2025. Seventy-three studies met the eligibility criteria of this review. NAC has been employed as a physically loaded therapeutic agent, covalently conjugated polymer modifier, contributor to hydrogel crosslinking, metal-coordination ligand, and compound incorporated into nano- and microparticulate carriers dispersed in hydrogel. These approaches enable the modulation of gelation, swelling, adhesion, degradation, and drug-release kinetics. NAC-containing hydrogels have demonstrated robust antioxidant, antimicrobial, antibiofilm, anti-inflammatory, angiogenic, and tissue-regenerative properties in various in vitro and in vivo models, underscoring their potential for advanced biomaterial applications. Release profiles varied from rapid stimulus-responsive delivery to sustained release over several days, depending on the network architecture and the NAC-matrix interactions. However, comparisons among studies were limited by the heterogeneous formulations, release conditions, biological models, and outcome measures. Standardized physicochemical characterization, NAC stability assessment, dose-response evaluation, and rigorous preclinical validation are required to support the translation of NAC-based hydrogels into biomedical applications. We hope that this review will help scientists and innovation centers understand the potential of the NAC-containing hydrogel biomaterials discussed in this study, as well as the opportunities and demands for additional research in this field.},
}

@article {pmid42614921,
year = {2026},
author = {Uchida, Y and Hirao, Y and Kurokawa, K and Ichikawa, Y and Furusho, S and Ogawa, H},
title = {Inhaled N-Acetylcysteine as a Potential Adjunctive Therapy in Mucus Plug-Forming Asthma With Irpex lacteus Isolation: A Case Report.},
journal = {Respirology case reports},
volume = {14},
number = {8},
pages = {e70723},
pmid = {42614921},
issn = {2051-3380},
abstract = {A 68-year-old woman was hospitalized for hypoxemia during an asthma exacerbation with cough, highly tenacious sputum and exertional dyspnoea. Chest computed tomography revealed lower lobe-dominant mucus plugs. Irpex lacteus was identified from both sputum culture and environmental sampling from the patient's bedroom, although diagnostic criteria for allergic bronchopulmonary mycosis were not fulfilled. Wheezing improved after standard therapy; however highly tenacious sputum persisted. Following administration of inhaled N-acetylcysteine (NAC), sputum tenacity improved, followed by improvements in respiratory symptoms, pulmonary function test values and flow-volume curves and the resolution of mucus plugs. This case suggests that highly tenacious sputum may represent a treatable trait in mucus plug-forming asthma and that inhaled NAC may serve as a useful adjunctive therapy in selected patients. Further accumulation of cases is needed to clarify the clinical significance of Irpex lacteus colonisation.},
}

@article {pmid42614177,
year = {2026},
author = {Filipowicz, AR and Bui, K and Osman, N and Morton, KS and Kenny-Ganzert, IW and Sherwood, DR and Meyer, JN and Allard, P},
title = {Dopaminergic neuronal dysfunction induced by newer generation systemic insecticides in Caenorhabditis elegans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.14.732178},
pmid = {42614177},
issn = {2692-8205},
abstract = {While a growing number of studies have linked environmental exposures and Parkinson's disease (PD) [1-3] , the impact of many pesticides remains understudied [4,5] ; for example, neonicotinoids are the most used insecticides in the world, but research into their contribution to PD is limited to a handful of studies [6-8] . Newer pesticides, such as the butenolide flupyradifurone (FPF), specifically developed to overcome increased pest resistance [9] and spurred on by tighter restrictions on neonicotinoids such as imidacloprid (IMI) [10] , are even less studied. New approach methodologies (NAMs) that allow for rapid evaluation of pesticide exposures are needed to evaluate potential links between the growing number of pesticides and PD [11] . To this end, we exposed the model nematode Caenorhabditis elegans [12] to IMI and FPF. Due to its high degree of tractability, and conservation of many genetic, neuronal, and toxic mode of action processes, C. elegans has been invaluable in both elucidating mechanisms and novel therapeutic targets for PD that can be validated in other models [13] , and as a complementary tool for early toxicity screening [14] . Along this line, we found that exposure to IMI, and to a greater extent FPF, in young adult animals causes significant dendritic blebbing, an early sign of neurodegeneration, exclusively in dopaminergic neurons. Blebbing was accompanied by impairment of dopamine-mediated behaviors, changes in neuronal mitochondrial morphology, and elevation of pathways related to reactive oxygen species (ROS). We were able to reduce the blebbing caused by IMI and FPF two ways: 1) pharmacologically via administration of the antioxidant N-acetyl cysteine (NAC); 2) genetically via knockout of a MAP kinase (MAPK) stress response pathway. This suggests that oxidative stress is a key mediator of this insecticide-induced dopaminergic neurodegeneration.},
}

@article {pmid42613941,
year = {2026},
author = {Orta Yilmaz, B and Sarialioglu, I and Elmaci, G and Aydin, Y},
title = {Antioxidant efficacy of N-acetylcysteine against acrylamide-induced toxicity in Leydig cells by modulating p53/Bax/Caspase-3 pathway.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/01480545.2026.2718396},
pmid = {42613941},
issn = {1525-6014},
abstract = {Acrylamide (Acr) is a widely encountered environmental and dietary toxicant known to induce oxidative stress and disrupt male reproductive function. Leydig cells, due to their high metabolic activity and mitochondrial dependence, are particularly vulnerable to redox imbalance. N-acetylcysteine (Nac), a thiol-containing antioxidant and glutathione precursor, has been extensively studied for its cytoprotective properties. However, its modulatory effects on Acr-induced toxicity in Leydig cells and its pharmacodynamic interaction profile remain incompletely characterized. In this study, TM3 Leydig cells were exposed to Acr in the presence or absence of Nac. Cell viability was assessed by MTT assay, and chemical interaction profiles were evaluated using ZIP, Bliss, and Chou-Talalay combination index analyses. Oxidative stress parameters, including intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant enzyme activities (SOD, CAT, GPx), and glutathione levels, were measured. Apoptotic responses were analyzed through double fluorescence staining, RT-qPCR of apoptosis-related genes (Bax, Bcl2, Casp3, Trp53), and Western blot analysis of CASP3 protein expression. Acr exposure significantly reduced cell viability, increased ROS and lipid peroxidation levels, suppressed antioxidant defenses, and activated the mitochondrial apoptotic pathway. Nac treatment markedly improved cell viability, restored antioxidant capacity, reduced oxidative stress markers, and suppressed p53/Bax/Casp3-mediated apoptotic signaling. Combination analyses revealed an antagonistic interaction profile, indicating that Nac biologically limits Acr-induced cytotoxicity. Collectively, these findings demonstrate that Nac exerts protective effects in Leydig cells by modulating redox homeostasis and mitochondrial apoptosis, suggesting its potential as a protective regulator against Acr-induced reproductive toxicity.},
}

@article {pmid42607897,
year = {2026},
author = {Xie, D and Yang, M and Cheng, S and An, B and Su, L and Sun, F and Huang, S and Luo, H},
title = {Prdx2 suppresses the erythroid differentiation by modulating the ROS-JNK1 signaling axis.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1873},
number = {1},
pages = {168422},
doi = {10.1016/j.bbadis.2026.168422},
pmid = {42607897},
issn = {1879-260X},
abstract = {Erythroleukemia is a rare but aggressive subtype of acute myeloid leukemia with a poor prognosis and limited therapeutic options. Impaired erythroid differentiation is a hallmark of this disease, yet the underlying molecular mechanisms remain incompletely understood. Peroxiredoxin 2 (PRDX2), a key antioxidant enzyme involved in maintaining cellular redox homeostasis, has been implicated in various solid tumors, but its role in erythroleukemia pathogenesis has not been explored. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile the bone marrow microenvironment of Friend murine leukemia virus (F-MuLV)-induced erythroleukemia mice. Integrated analysis identified PRDX2 as a significantly upregulated molecule across multiple malignant cell populations. Elevated PRDX2 expression in leukemic bone marrow was accompanied by decreased intracellular reactive oxygen species (ROS) levels, suggesting a potential link between PRDX2-mediated redox regulation and erythroleukemia progression. Functional assays in human erythroleukemia cell lines K562 and HEL demonstrated that PRDX2 knockdown inhibited cell accumulation, increased apoptosis, and promoted erythroid differentiation. Mechanistically, PRDX2 knockdown elevated ROS levels, and treatment with the ROS inhibitor N-acetylcysteine (NAC) reversed both ROS elevation and differentiation. Furthermore, PRDX2 depletion selectively activated the JNK1 pathway, with no changes in p38, ERK, or mTOR signaling. NAC treatment reversed JNK1 activation, indicating that ROS modulates differentiation through JNK1. Consistently, treatment with a JNK1 inhibitor reversed the differentiation induced by PRDX2 knockdown, confirming that JNK1 activation is functionally required. Collectively, our findings establish PRDX2 as a critical regulator of erythroid differentiation blockade and identify PRDX2 as a promising pharmacologically actionable target for differentiation-based therapy in erythroleukemia.},
}

@article {pmid42609061,
year = {2026},
author = {Huang, J and Huang, H and Huang, K and Fang, B and Bi, X and Huang, S and Su, H and Li, J},
title = {Rapidly Liver-Accumulating BiOCl@ITA Nanozyme for Synergistic ROS Scavenging and Macrophage Reprogramming in APAP-Induced Liver Injury.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.6c08667},
pmid = {42609061},
issn = {1944-8252},
support = {2025GXNSFAA069423//Natural Science Foundation of Guangxi Zhuang Autonomous Region/ ; 2025A04J4367//Guangzhou Municipal Science and Technology Project/ ; 20251A011007//Guangzhou Municipal Health and Family Planning Commission/ ; },
abstract = {Acetaminophen (APAP) overdose is the leading cause of acute liver failure worldwide, yet existing therapy relies solely on N-acetylcysteine (NAC), whose efficacy diminishes markedly beyond an 8-10 h therapeutic window. The underlying pathology involves a self-amplifying cycle of reactive oxygen species (ROS) overproduction and macrophage-mediated inflammation, and strategies that concurrently scavenge ROS, reprogram macrophage polarization, and attenuate hepatocyte apoptosis remain lacking. Itaconate (ITA), an endogenous anti-inflammatory metabolite, suffers from poor membrane permeability and lacks intrinsic ROS-scavenging capacity. Herein, we constructed BiOCl@ITA by integrating defect-engineered bismuth oxychloride (BiOCl) with surface-loaded ITA. Oxygen vacancy engineering confers intrinsic superoxide dismutase (SOD)- and catalase (CAT)-mimicking activities under stimulus-free conditions. BiOCl@ITA showed rapid accumulation in the liver within 0.5 h after intraperitoneal administration and was efficiently internalized by both hepatocytes and macrophages in vitro. Moreover, BiOCl@ITA virtually eliminated intracellular ROS and attenuated APAP-induced hepatocyte injury, while also reprogramming LPS-stimulated macrophages from M1 toward an M2 phenotype, consistently outperforming free ITA across all endpoints. In a murine APAP-induced ALI model, BiOCl@ITA-treated mice showed near-complete thermal recovery by 24 h, accompanied by substantially reduced serum hepatic injury markers and attenuated histopathological damage. Hepatic molecular and tissue-level analyses further demonstrated restoration of antioxidant defenses, favorable regulation of BAX/BCL-2 expression, and sustained M1-to-M2 macrophage polarization in vivo. These findings demonstrate that BiOCl@ITA synergistically integrates catalytic ROS detoxification with ITA-mediated macrophage reprogramming, offering a promising therapeutic approach for APAP-induced acute liver injury.},
}

@article {pmid42609818,
year = {2026},
author = {Nguyen, TH and Nguyen, VN and Nguyen, HTT and Nguyen, HN and Nguyen, AD and Nguyen, TV and Nguyen, TX},
title = {Synthesis of carbon dot-mediated gold nanostructures: experimental and quantum chemical insights into turn-on fluorescence sensing of N-acetylcysteine.},
journal = {Beilstein journal of nanotechnology},
volume = {17},
number = {},
pages = {1103-1116},
pmid = {42609818},
issn = {2190-4286},
abstract = {In this work, a green and sustainable hydrothermal approach was employed to synthesize nitrogen-doped carbon dots (NCDs) using lemon juice as a natural precursor. The as-prepared NCDs served as eco-friendly reducing agents and stabilizing scaffolds for the subsequent in situ synthesis of gold nanoparticles (Au@NCDs). The structural and optical properties of the nanocomposite were comprehensively characterized using various analytical techniques. The intrinsic fluorescence of NCDs was significantly quenched upon formation of the composite, mainly due to non-radiative energy transfer processes. Interestingly, the quenched fluorescence could be efficiently restored upon the addition of N-acetylcysteine (NAC), enabling the development of an "off-on" fluorescent sensing platform. The sensing mechanism was systematically elucidated through a combination of spectroscopic studies and density functional theory calculations, revealing that fluorescence recovery originates from a ligand exchange process driven by the stronger binding affinity of NAC toward the gold surface, particularly via Au-S interactions. Under optimized conditions, the assay exhibited a robust linear response for NAC concentrations ranging from 4.0 to 20.0 mg/L, with a detection limit of 0.863 mg/L. These results demonstrate that the Au@NCDs system can function as a sensitive and selective OFF-ON fluorescent probe for NAC detection. This study provides a cost-effective and eco-friendly sensing platform with significant potential for analytical applications in pharmaceutical monitoring.},
}

@article {pmid42611259,
year = {2026},
author = {Ren, Y and Song, Y and Lu, H and Mei, F and Wang, Z and Liang, Y and Zhong, J and Zheng, R and Du, B and Jiang, X},
title = {Boosting Cellular Glutathione Accelerates Elimination of Engineered Ultrasmall Nanoparticles from Kidneys and Liver by Promoting Exosome Release.},
journal = {ACS nano},
volume = {20},
number = {32},
pages = {22517-22529},
doi = {10.1021/acsnano.6c03801},
pmid = {42611259},
issn = {1936-086X},
support = {22275056//National Natural Science Foundation of China/ ; 22574056//National Natural Science Foundation of China/ ; 2023YFB3810300//National Key Research and Development Program of China/ ; 2024D01J0054//GJYC program of Guangzhou/ ; },
mesh = {*Glutathione/metabolism ; Animals ; *Exosomes/metabolism ; *Liver/metabolism/drug effects ; Mice ; *Kidney/metabolism/drug effects ; Acetylcysteine/pharmacology/administration & dosage ; *Metal Nanoparticles/chemistry ; *Gold/chemistry/metabolism ; Particle Size ; Humans ; Male ; },
abstract = {Being two major detoxifying organs for in vivo clearance of nanoparticles, the kidneys and liver are susceptible to prolonged accumulation of engineered nanoparticles and associated side effects, particularly for the nondegradable ones. Thus, strategies that expedite the elimination of accumulated nanoparticles from these organs are in high demand. Herein, using two engineered ultrasmall gold nanoparticles that respectively accumulate in the kidneys and liver as models, we showed that orally supplementing N-acetylcysteine (NAC), a clinical drug and precursor of glutathione (GSH), significantly accelerated the elimination of accumulated ultrasmall gold nanoparticles in the kidneys and liver while promoting their renal and hepatobiliary excretion in mice. This enhanced elimination effect stemmed from NAC-induced elevation of intracellular GSH levels, which facilitates endocytosed ultrasmall nanoparticles to be exocytosed via exosomes instead of prolonged trapping in the lysosomes, a mechanism distinct from the conventional transporter-mediated export of small-molecule xenobiotics through GSH conjugation. Moreover, this promotion of exosome release was found to be independent of nanoparticle treatment but a natural cellular response to boosted GSH levels by NAC. Our findings thus demonstrate NAC supplementation as a potential strategy for accelerating the excretion of ultrasmall nanoparticles from the kidneys and liver, offering insights into the role of GSH in facilitating cellular elimination of substances.},
}

*Glutathione/metabolism
Animals
*Exosomes/metabolism
*Liver/metabolism/drug effects
Mice
*Kidney/metabolism/drug effects
Acetylcysteine/pharmacology/administration & dosage
*Metal Nanoparticles/chemistry
*Gold/chemistry/metabolism
Particle Size
Humans
Male

@article {pmid42604715,
year = {2026},
author = {Liu, X and Feng, C and Zhu, T and Qin, Z and Han, Y and Wang, Y and Li, X and Suo, Y},
title = {Aspartame triggers premature ovarian failure via SIRT1-dependent suppression of the PI3K/AKT/mTOR pathway and induction of oxidative stress and apoptosis.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1873},
number = {1},
pages = {168425},
doi = {10.1016/j.bbadis.2026.168425},
pmid = {42604715},
issn = {1879-260X},
abstract = {Given concerns about the reproductive safety of aspartame, this study investigated aspartame-induced premature ovarian failure (POF) using integrated computational biology, in vitro, and in vivo approaches. Network toxicology identified 182 overlapping targets, which were mainly enriched in oxidative stress (OS), apoptosis, and the PI3K/AKT/mTOR pathway. Molecular dynamics (MD) simulations initially predicted that SIRT1 had the highest binding affinity for aspartame, and this interaction was further validated by surface plasmon resonance (SPR) analysis. In vitro experiments using KGN cells showed that aspartame suppressed cell proliferation in a time- and concentration-dependent manner. RNA sequencing (RNA-seq) revealed SIRT1 downregulation and enrichment of related pathways. Further in vitro experiments demonstrated that aspartame inhibited SIRT1 and the PI3K/AKT/mTOR pathway, increased ROS levels, and promoted apoptosis; these effects were reversed by SIRT1 overexpression. Parallel in vivo studies showed that oral administration of aspartame to rats at 30-120 mg/kg for 8 weeks disrupted the estrous cycle, induced hormonal imbalance, caused follicular dysplasia, increased follicular atresia, and reduced ovarian reserve. Ovarian immunohistochemistry (IHC) further confirmed apoptotic damage. To further clarify the driving role of OS, assays utilizing serum from aspartame-treated mice combined with N-acetylcysteine (NAC) showed that ROS elevation and subsequent apoptosis were significantly reversed by NAC treatment. Collectively, these findings suggest that aspartame exposure contributes to POF, with direct suppression of the SIRT1/PI3K/AKT/mTOR pathway representing a key molecular mechanism underlying its intrinsic toxicity and aggravating OS-related apoptosis. This study provides mechanistic evidence for the reproductive toxicity of aspartame and supports the need for further risk assessment and exposure control to reduce the risk of POF.},
}

@article {pmid42607555,
year = {2026},
author = {Bao, Z and Zhang, G and Shao, M and Chen, J and Wei, Z and Zhang, C and Zhang, J and Hu, D and Xu, H and Zhang, L},
title = {Gaudichaudione H induces GSDME-mediated pyroptosis and apoptosis in esophageal squamous cell carcinoma via ROS-dependent YAP degradation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {160},
number = {},
pages = {158677},
doi = {10.1016/j.phymed.2026.158677},
pmid = {42607555},
issn = {1618-095X},
abstract = {BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with limited therapeutic options. Therefore, novel treatment strategies are urgently needed.

PURPOSE: This study aimed to evaluate the antitumor effects of Gaudichaudione H (GH), a natural caged xanthone isolated from Garcinia oligantha Merr., and to elucidate its underlying mechanisms with a focus on cell death regulation in ESCC.

METHODS: The antitumor activity of GH was evaluated in ESCC cell lines (KYSE150, KYSE450, Eca-109) and a xenograft mouse model. Cell viability, LDH release, morphological changes, and protein expression were assessed. RNA sequencing, pharmacological inhibitors, and genetic manipulation of YAP (knockdown and overexpression) were used to investigate the underlying mechanism.

RESULTS: GH exhibited dose-dependent cytotoxicity against ESCC cell lines, with IC₅₀ values ranging from 5.7 to 7.9 μM in KYSE150, KYSE450, and Eca-109 cells. GH induced apoptotic and pyroptotic morphological features accompanied by increased LDH release in a caspase-3-dependent manner. Transcriptomic analysis revealed enrichment of the MAPK/JNK signaling pathway. Mechanistically, GH elevated intracellular ROS levels, leading to ubiquitin-proteasome-dependent degradation of YAP. Loss of YAP activated JNK signaling, resulting in caspase-3 activation and GSDME cleavage. ROS scavenging or JNK inhibition significantly attenuated GH-induced cell death. In vivo, GH inhibited tumor growth by approximately 75% compared with the vehicle-treated group in a xenograft model without observable systemic toxicity.

CONCLUSION: GH induces ESCC cell death through a ROS-dependent YAP ubiquitination axis involving JNK signaling activation, which regulates the crosstalk between apoptosis and pyroptosis in ESCC. These findings highlight GH as a promising natural lead compound for ESCC therapy.

ABBREVIATIONS: CHX, Cycloheximide; DMSO, Dimethyl sulfoxide; ECL, Enhanced chemiluminescence; ESCC, Esophageal squamous cell carcinoma; GSDME, Gasdermin E; GH, Gaudichaudione H; JNK, c-Jun N-terminal kinase; KEGG, Kyoto Encyclopedia of Genes and Genomes; LDH, Lactate dehydrogenase; MAPK, Mitogen-activated protein kinase; NAC, N-acetylcysteine; PARP, Poly(ADP-ribose) polymerase; PBS, Phosphate-buffered saline; PCD, Programmed cell death; PPI, Protein-protein interaction; RNA-seq, RNA sequencing; ROS, Reactive oxygen species; siRNA, Small interfering RNA; YAP, Yes-associated protein.},
}

@article {pmid42607812,
year = {2026},
author = {Ha, SG and Park, M and Lee, J and Bong, D and Ahn, J and Kim, D and Kim, MO and Lee, SV and Ha, NC},
title = {Excessive disulfide bonds in Lamin A/C contribute to premature human aging.},
journal = {Molecules and cells},
volume = {},
number = {},
pages = {100389},
doi = {10.1016/j.mocell.2026.100389},
pmid = {42607812},
issn = {0219-1032},
abstract = {Nuclear lamins provide structural integrity to the nuclear envelope through coiled-coil dimer meshworks. Lamin A contains a C-terminal immunoglobulin (Ig)-like domain and a cysteine-rich unstructured tail, whereas lamin C lacks the latter, retaining only one cysteine within the Ig-like domain. Mutations R435C and R471C in the Ig-like domain are linked to progeroid syndromes, fatal disorders characterized by premature aging. Here, we elucidate a pathogenic mechanism driven by aberrant disulfide cross-linking. We found that the R435C mutation, but not R471C, facilitates successive disulfide bond formation between Ig-like domains in vitro using purified recombinant proteins, causing nuclear deformation in lamin C-overexpressing cells. In lamin A-overexpressing cells, both R435C and R471C mutations induce additional intermolecular disulfide bonds involving the lamin A-specific cysteine residues in the C-terminal tail. Importantly, we demonstrate that glutathione and its precursor, N-acetyl cysteine, can disrupt these aberrant bonds. Using Caenorhabditis elegans as an in vivo model, we show that the orthologous cysteine mutation causes progeria phenotypes, which are suppressed by antioxidant treatment. These findings identify aberrant disulfide cross-linking as a key driver of progeria and suggest antioxidant therapies as a potential treatment strategy. Our study offers broader implications for vertebrate aging, suggesting that oxidative stress-mediated changes in lamin architecture are a conserved mechanism contributing to the loss of nuclear structural integrity and age-dependent nuclear aberration.},
}

@article {pmid42592990,
year = {2026},
author = {Gavrankapetanovic, A and Valjevac, A and Dervisevic, A and Alic, L and Ibrahimovic, S and Kukuljac, A and Letić, E},
title = {Serum interleukin-6 is not associated with postoperative intra-abdominal adhesion severity in a rat model.},
journal = {Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina},
volume = {23},
number = {2},
pages = {},
doi = {10.17392/medglas-2185-23-2},
pmid = {42592990},
issn = {1840-2445},
mesh = {Animals ; *Interleukin-6/blood ; Male ; Tissue Adhesions/blood/drug therapy ; Rats, Wistar ; Tissue Plasminogen Activator/administration & dosage/pharmacology ; Acetylcysteine/administration & dosage/pharmacology ; Rats ; Disease Models, Animal ; *Postoperative Complications/blood/drug therapy ; Biomarkers/blood ; Fibrinolytic Agents/administration & dosage ; Severity of Illness Index ; },
abstract = {AIM: To assess whether serum interleukin-6 (IL-6) measured on postoperative day 14 reflects adhesion severity and to compare intraperitoneal alteplase, N-acetylcysteine (NAC), and combined treatment.

METHODS: In this exploratory randomised study, 40 male Wistar rats were allocated to untreated adhesion, alteplase, NAC, alteplase plus NAC, or sham groups (n = 8 per group). Serum IL-6 and macroscopic adhesion grade were assessed on day 14. Group differences were analysed using the Kruskal-Wallis tests followed by Benjamini-Hochberg-adjusted Dunn comparisons; associations were assessed using Spearman correlation.

RESULTS: Serum IL-6 differed among groups (H = 18.08; p = 0.001). Median serum IL-6 concentrations were 14.52 pg/mL (IQR 9.91-19.13) in untreated animals, 30.70 pg/mL (IQR 27.31-34.09) after alteplase (p = 0.003), 24.95 pg/mL (IQR 17.48-32.42) after NAC (p = 0.037), 30.76 pg/mL (IQR 24.16-37.36) after combined treatment (p = 0.007), and 18.36 pg/mL (IQR 11.49-25.23) in sham animals (p = 0.320). Adhesion grades differed (H = 20.80; p < 0.001) and were lower after alteplase and combined treatment (both p = 0.041); the NAC comparison was not significant (p = 0.054). Serum IL-6 was not correlated with adhesion grade (ρ = -0.131; 95% CI -0.425 to 0.189; p = 0.422).

CONCLUSION: A single serum IL-6 measurement on day 14 did not reflect adhesion severity. Serial serum measurements and concurrent peritoneal or tissue biomarkers may be more informative.},
}

Animals
*Interleukin-6/blood
Male
Tissue Adhesions/blood/drug therapy
Rats, Wistar
Tissue Plasminogen Activator/administration & dosage/pharmacology
Acetylcysteine/administration & dosage/pharmacology
Rats
Disease Models, Animal
*Postoperative Complications/blood/drug therapy
Biomarkers/blood
Fibrinolytic Agents/administration & dosage
Severity of Illness Index

@article {pmid42593897,
year = {2026},
author = {Mayer, SK and Christensen, QH and McCoy-Munger, H and Mohar, NP and Botero, V and Tomchik, SM and Rong, Y and Drack, AV and Wallrath, LL},
title = {N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa.},
journal = {Human molecular genetics},
volume = {35},
number = {17},
pages = {},
doi = {10.1093/hmg/ddag077},
pmid = {42593897},
issn = {1460-2083},
support = {P40OD018537/NH/NIH HHS/United States ; },
mesh = {Animals ; *Retinitis Pigmentosa/genetics/drug therapy/pathology/metabolism ; *Acetylcysteine/pharmacology ; *Ribonucleoproteins, Small Nuclear/genetics/metabolism ; Disease Models, Animal ; Humans ; Drosophila melanogaster/genetics ; Mutation ; Retina/metabolism/drug effects/pathology ; Apoptosis/drug effects ; Drosophila Proteins/genetics ; },
abstract = {Retinitis Pigmentosa (RP) is an inherited retinal degenerative disease that affects 1 in 4000 individuals worldwide and can lead to complete blindness. Early stages of RP involve death of rod photoreceptors via apoptosis, causing loss of peripheral and night vision, which is followed by death of cone photoreceptors, leading to loss of central and daytime vision. Mutations in over 300 genes cause RP. Many of these genes encode retina-specific proteins; however, some encode globally expressed proteins, such as pre-mRNA splicing factors. This study is focused on mutations in the SNRNP200 gene encoding a core pre-mRNA splicing factor. The pathological mechanisms of SNRNP200-associated RP are not well understood and treatments are limited. An approach to study pathogenic mechanisms is to utilize model organisms. Therefore, we developed Drosophila models in which RP-causing mutations were introduced into the Drosophila melanogaster orthologue Snrnp200. In addition, we used RNAi to knock-down Snrnp200 in the developing eye. Depletion of Snrnp200 caused an adult rough eye phenotype due to apoptosis of cells in the retina. When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors. Further analysis of the photoreceptors revealed mitochondrial defects and altered expression of genes related to redox homeostasis. Consistent with these changes, treatment with the antioxidant N-acetylcysteine (NAC) partially suppressed the photoreceptor defects. Taken together, these findings established a new genetic model for studies of splicing-factor associated RP that recapitulates aspects of the human disease and suggests that antioxidants might serve as a treatment for individuals with SNRNP200-associated RP.},
}

Animals
*Retinitis Pigmentosa/genetics/drug therapy/pathology/metabolism
*Acetylcysteine/pharmacology
*Ribonucleoproteins, Small Nuclear/genetics/metabolism
Disease Models, Animal
Humans
Drosophila melanogaster/genetics
Mutation
Retina/metabolism/drug effects/pathology
Apoptosis/drug effects
Drosophila Proteins/genetics

@article {pmid42600284,
year = {2026},
author = {Shao, W and Zhou, W and Sheng, Y and Zhu, W and Wang, G and Zhang, C and Kang, X and Hu, R},
title = {Research on the effect of N-acetylcysteine on ROS/NLRP3-mediated pyroptosis in BEAS-2B Cells and bronchial epithelial tissues from patients with AECOPD.},
journal = {Immunobiology},
volume = {231},
number = {5},
pages = {153231},
doi = {10.1016/j.imbio.2026.153231},
pmid = {42600284},
issn = {1878-3279},
abstract = {OBJECTIVE: This study investigated the impact of cigarette smoke extract (CSE) on BEAS-2B bronchial epithelial cells, focusing on whether it induces pyroptosis via the ROS/NLRP3/GSDMD pathway and how NAC protects these cells from pyroptosis.

METHODS: BEAS-2B cells were treated with varying CSE concentrations, and cellular damage was evaluated via PI staining and release of ROS and LDH. Cellular morphology alterations were examined by immunohistochemistry, and IL-18 and IL-1β release were measured by ELISA. Western blot analysis was used to assess expression of proteins linked to pyroptosis, including ASC, NLRP3, cleaved-caspase-1, GSDMD-N, and IL-1β. Caspase-1 and GSDMD inhibitors were utilized to elucidate the underlying mechanisms.

RESULTS: Following CSE treatment, bronchial epithelial cells demonstrated inflammatory infiltration and membrane rupture and increased ROS, NLRP3, cleaved-caspase-1, GSDMD-N, IL-18, and IL-1β expression. Treatment with caspase-1 and GSDMD inhibitors decreased expression of these markers, as expected. Interestingly, NAC treatment reduced the expression of these proteins compared to the CSE group, suggesting a protective role against pyroptosis through inhibition of the ROS/NLRP3/GSDMD pathway.

CONCLUSION: The study shows that CSE triggers pyroptosis in COPD via the ROS/NLRP3/GSDMD pathway, with NAC offering antioxidative protection. These findings enhance understanding of AECOPD pathophysiology and support NAC's therapeutic role in treatment.},
}

@article {pmid42584395,
year = {2026},
author = {Ni, P and Zhang, Q and Jiang, Y and Yao, H and Zhou, C and Tian, X and Gao, S and Zhao, J and Ren, X and Xu, N and Fu, M and Zhao, L and Qi, X and Yu, X and Guo, W and Chung, S and Guo, F and Li, T},
title = {Gestational Hypoxia Disrupts Medial Ganglionic Eminence Progenitor Dynamics and Interneuron Development in Schizophrenia.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76936},
pmid = {42584395},
issn = {2198-3844},
support = {2024WJC035//Hangzhou Special Project for Biomedical and Health Industry/ ; 2025HZGF10//The Construction Fund of Medical Disciplines of Hangzhou/ ; 20241203A14//the Key R&D by Hangzhou Science and Technology Bureau/ ; 82571737//National Natural Science Foundation of China/ ; MH131610/MH/NIMH NIH HHS/United States ; MH133205/MH/NIMH NIH HHS/United States ; 2024E10107//Zhejiang Key Laboratory of Clinical and Basic Research for Psychiatric Diseases/ ; R01 MH133205/MH/NIMH NIH HHS/United States ; R01 MH131610/MH/NIMH NIH HHS/United States ; 82230046//National Natural Science Foundation of China/ ; 2025C02112//Key R&D Program of Zhejiang/ ; 2024ZY01010//Zhejiang Key Laboratory of Clinical and Basic Research for Psychiatric Diseases/ ; },
abstract = {Schizophrenia (SCZ) is a neurodevelopmental disorder characterized by heterogeneous symptoms and multifactorial etiologies. Medial ganglionic eminence (MGE) spheroids generated from first-episode schizophrenia (FES) patients revealed accelerated neurodevelopmental trajectories and enhanced hypoxia responses via single-cell transcriptomics. Notably, FES patient-derived MGE spheroids exhibited defective interneuron migration, disrupted synaptic ultrastructure, and diminished network synchronization. To establish causal links, the gestational hypoxia mouse model recapitulated key pathologies, including reduced progenitor proliferation, abbreviated cell cycles, mismatched interneuron subtypes, and schizophrenia-like behavioral deficits in offspring. Critically, maternal administration of N-acetylcysteine (NAC) restored redox homeostasis and rescued both cellular and behavioral phenotypes. Collectively, these results demonstrate that developmental redox disruption directly impairs GABAergic circuit assembly, while supporting targeted antioxidant pharmacotherapy during gestation as a translatable strategy to mitigate neurodevelopmental risk.},
}

@article {pmid42586276,
year = {2026},
author = {Guo, R and Ding, Q and Pei, L and Liu, Q and Guo, Z and Cao, F and Zhang, C and Li, X and Song, Z and Wang, H and Liu, Q and Li, S},
title = {APCS is a redox-sensitive regulator linking miR-24-2-5p to AMPK suppression and alcohol-induced hepatic steatosis.},
journal = {Free radical biology & medicine},
volume = {255},
number = {},
pages = {843-857},
doi = {10.1016/j.freeradbiomed.2026.07.048},
pmid = {42586276},
issn = {1873-4596},
abstract = {Chronic alcohol consumption promotes hepatic steatosis, a key feature of alcohol-associated liver disease (ALD), yet the signaling mechanisms linking oxidative stress to lipid dysregulation remain incompletely understood. Here, we identify amyloid P component (APCS) as a previously unrecognized, alcohol-repressed hepatoprotective factor that is consistently suppressed during ALD progression. Transcriptomic, biochemical, and histological analyses revealed markedly reduced APCS expression in the livers of ALD patients and alcohol-fed mice, as well as in ethanol-treated hepatocytes. Functional studies demonstrated that liver-specific APCS deficiency increases susceptibility to alcohol-induced hepatic steatosis in vivo and promotes lipid accumulation in hepatocytes. Mechanistically, we identified miR-24-2-5p as an alcohol-inducible microRNA that directly targets Apcs. Manipulation of miR-24-2-5p reciprocally regulated APCS expression and hepatocellular lipid accumulation. Further analyses revealed that the miR-24-2-5p/APCS axis modulates AMPK activity, potentially through regulation of mitochondrial function, cellular redox homeostasis, and cAMP-associated signaling pathways. APCS depletion reduced AMPK phosphorylation and activity, whereas inhibition of miR-24-2-5p restored AMPK signaling. Pharmacological modulation confirmed AMPK as a critical downstream effector mediating the lipogenic effects associated with APCS deficiency. Importantly, antioxidant intervention with N-acetylcysteine (NAC) attenuated alcohol-induced miR-24-2-5p upregulation, restored APCS expression, and reactivated AMPK both in vivo and in vitro, whereas pro-oxidant stimuli recapitulated these regulatory effects. Collectively, these findings define an oxidative stress-driven miR-24-2-5p/APCS/AMPK regulatory axis that governs alcohol-induced hepatic steatosis and highlight a potential therapeutic target for ALD.},
}

@article {pmid42587287,
year = {2026},
author = {Ramadan, AM and El-Wakeel, LM and Adel, A and Abdel-Wahab, M and Fahmy, SF},
title = {Effect of high dose N-acetyl cysteine supplementation on markers of oxidative stress and insulin resistance in non-diabetic patients with metabolic dysfunction associated steatotic liver disease: a randomized controlled trial.},
journal = {BMC gastroenterology},
volume = {26},
number = {1},
pages = {},
pmid = {42587287},
issn = {1471-230X},
mesh = {Humans ; *Acetylcysteine/administration & dosage ; *Oxidative Stress/drug effects ; *Insulin Resistance ; Male ; Female ; Middle Aged ; Prospective Studies ; Malondialdehyde/blood ; Biomarkers/blood ; Adult ; *Non-alcoholic Fatty Liver Disease/drug therapy/blood/therapy ; Quality of Life ; Insulin/blood ; Leptin/blood ; *Antioxidants/administration & dosage ; Life Style ; Liver Cirrhosis ; },
abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease. N-acetylcysteine (NAC) has demonstrated antioxidant and hepatoprotective effects in non-alcoholic steatohepatitis. This study evaluated the impact of high-dose NAC on oxidative stress, insulin resistance, and liver-related outcomes in non-diabetic MASLD patients.

METHODS: This prospective, randomized, open-label controlled trial included 60 non-diabetic adults with MASLD. Participants were randomly assigned to receive either oral NAC (2400 mg/day) combined with lifestyle intervention (n = 30) or lifestyle intervention alone (n = 30) for 12 weeks. The primary outcome was change in serum malondialdehyde (MDA). Secondary outcomes included markers of insulin resistance (leptin, fasting insulin, and HOMA-IR), lipid profile, liver steatosis and fibrosis assessed by FibroScan[®] and non-invasive scores, and quality of life (QOL).

RESULTS: No significant differences in serum MDA, leptin, fasting insulin, or HOMA-IR (all p > 0.05) between groups. Similarly, FibroScan[®] parameters, non-invasive steatosis and fibrosis scores did not differ significantly between groups. A significant reduction in liver steatosis scores in the control group (p = 0.004) while the Hepatic steatosis index improved in both groups (p = 0.008).Triglyceride levels decreased significantly in the control group, whereas HDL-cholesterol increased significantly in the NAC group. QOL scores remained unchanged overall, except for a significant increase in the emotional domain scores in the NAC group.

CONCLUSIONS: High-dose NAC for three months did not significantly improve oxidative stress, insulin resistance, or hepatic steatosis or fibrosis in non-diabetic MASLD patients. NAC was safe and well tolerated during the study period.

TRIAL REGISTRATION: This study was registered on clinicaltrials.gov under the identifier number NCT05589584 in October 2022.},
}

Humans
*Acetylcysteine/administration & dosage
*Oxidative Stress/drug effects
*Insulin Resistance
Male
Female
Middle Aged
Prospective Studies
Malondialdehyde/blood
Biomarkers/blood
Adult
*Non-alcoholic Fatty Liver Disease/drug therapy/blood/therapy
Quality of Life
Insulin/blood
Leptin/blood
*Antioxidants/administration & dosage
Life Style
Liver Cirrhosis

@article {pmid42581452,
year = {2026},
author = {Tu, YA and Chou, CH and Chang, K and Huang, CC and Ho, HN and Chen, MJ},
title = {Diet-Induced Obesity Promotes Alopecia Through Oxidative Stress and Androgen Signalling in Female Mice.},
journal = {Experimental dermatology},
volume = {35},
number = {8},
pages = {e70343},
pmid = {42581452},
issn = {1600-0625},
support = {113-E0002//National Taiwan University Hospital/ ; 114-E0006//National Taiwan University Hospital/ ; 112-2314-B-002-159-MY3//National Science and Technology Council/ ; 113-2314-B-002-033//National Science and Technology Council/ ; 114-2314-B-002-022//National Science and Technology Council/ ; },
mesh = {Animals ; Female ; *Oxidative Stress ; *Alopecia/etiology/metabolism ; *Obesity/complications/metabolism/etiology ; *Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Mice ; Dihydrotestosterone/metabolism ; Receptors, Androgen/metabolism ; Signal Transduction ; *Androgens/metabolism ; Malondialdehyde/metabolism ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism ; Skin/metabolism ; Finasteride/pharmacology ; },
abstract = {Female-pattern hair loss is common in obese women with polycystic ovary syndrome (PCOS), recently proposed as polyendocrine metabolic ovarian syndrome (PMOS) and is often associated with hypertriglyceridemia (TG), although the underlying mechanisms remain unclear. This study investigated how metabolic factors and androgens contribute to hair loss in female mice exposed to a high-fat diet (HFD). A controlled, parallel-group study using 8-week-old female C57BL/6 mice fed either an HFD (60% kcal fat) or a standard diet for 16 weeks. Mice were sacrificed at baseline and 4-week intervals for serial evaluation of metabolic, hormonal and skin changes (n = 6/group/time point). Hair loss was quantified from digital photographs using the ImageJ and further supported by histological examination. Circulating metabolic and hormonal profiles were measured. In dorsal skin, oxidative stress (malondialdehyde, MDA) and androgen-related markers-5-alpha-reductase type II (5αR2), dihydrotestosterone (DHT) and androgen receptor (AR)-were evaluated using immunohistochemistry, Western blot and enzyme-linked immunosorbent assay. From Week 12 onward, HFD-fed mice exhibited greater weight gain, pronounced dorsal hair thinning and elevated TG, insulin and free androgen index (FAI) levels. Skin MDA, 5αR2, DHT and AR levels also progressively increased. In the second experiment, 8-week-old female mice were assigned to four groups (n = 6/group): HFD with N-acetylcysteine (NAC), finasteride, spironolactone, or vehicle administered by oral gavage for 12 weeks. Compared with HFD-vehicle, antioxidant or anti-androgen co-treatment significantly lowered serum TG, tissue MDA and ameliorated hair thinning despite similar weight gain and 5αR2 levels. NAC reduced TG, FAI and decreased tissue MDA, DHT and AR. Finasteride lowered TG, MDA, DHT and AR, whereas spironolactone reduced TG and MDA. HFD-induced obesity exacerbates hair loss in female mice by enhancing oxidative stress and activating androgen signalling in the skin. Targeting these pathways, such as antioxidants and antiandrogens, may mitigate HFD-accelerated hair loss.},
}

Animals
Female
*Oxidative Stress
*Alopecia/etiology/metabolism
*Obesity/complications/metabolism/etiology
*Diet, High-Fat/adverse effects
Mice, Inbred C57BL
Mice
Dihydrotestosterone/metabolism
Receptors, Androgen/metabolism
Signal Transduction
*Androgens/metabolism
Malondialdehyde/metabolism
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism
Skin/metabolism
Finasteride/pharmacology

@article {pmid42577532,
year = {2026},
author = {Wang, H and Zhang, X and Li, J},
title = {Valproic acid sensitizes resveratrol to induce glioma cell apoptosis via the ROS-PDCD4-Bax signaling axis.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1886066},
pmid = {42577532},
issn = {2296-634X},
abstract = {BACKGROUND: Glioma is an aggressive malignant brain tumor with poor prognosis. Resveratrol (RES) possesses anti-tumor activity yet limited clinical value. Valproic acid (VPA), a histone deacetylase inhibitor, boosts multiple anti-cancer drugs' efficacy. This study explored RES/VPA synergy in glioma cell lines and syngeneic mouse tumors, and confirmed the reactive oxygen species (ROS)-programmed cell death protein 4 (PDCD4)-Bax cascade drives combined pro-apoptotic and anti-invasive effects.

METHODS: CCK-8 detected cell proliferation; morphology and AO/EB staining assessed apoptosis. Wound healing and transwell assays measured migration. Western blot analyzed apoptosis and migration-related proteins, including PDCD4. Dihydroethidium staining tested intracellular ROS. Rescue assays used N-acetylcysteine (NAC) and PDCD4 knockdown; subcutaneous syngeneic mice validated in vivo anti-tumor activity.

RESULTS: VPA alone exerted no significant cytotoxicity on glioma cells (p > 0.05 vs. NC), while RES inhibited U87MG and U251 cell proliferation in a concentration-dependent manner (p < 0.05, p < 0.01 vs. NC). RES/VPA co-treatment significantly enhanced cytotoxicity, suppressed migration and induced glioma cell apoptosis, with anti-tumor efficacy comparable to clinical doxorubicin (p > 0.05 Com vs. DOX; p < 0.01 Com vs. RES). Mechanistically, the combination markedly increased intracellular ROS accumulation (p < 0.001 Com vs. RES), upregulated PDCD4 expression (p < 0.01 Com vs. RES), and modulated apoptosis- and EMT-related protein levels to trigger cell apoptosis. NAC-mediated ROS scavenging or PDCD4 knockdown significantly abolished the synergistic pro-apoptotic effect of the combination therapy (p < 0.01 vs. Com), verifying the critical ROS-PDCD4 signaling function. In vivo, RES/VPA co-treatment significantly inhibited tumor growth (p < 0.01 Com vs. RES), and low-dose combination achieved equivalent efficacy to high-dose RES monotherapy (p > 0.05) without obvious toxic effects.

CONCLUSION: RES combined with VPA exerts synergistic anti-glioma effects via the ROS-PDCD4-Bax signaling pathway, providing experimental evidence for VPA as an adjuvant in RES-based therapy. This combinatorial strategy overcomes the insufficient anti-tumor potency of RES monotherapy at the cellular and murine tumor level, expands the preclinical antitumor research value of natural polyphenols, and provides laboratory experimental reference for subsequent translational exploration of glioma therapy.},
}

@article {pmid42579905,
year = {2026},
author = {Yang, Y and Li, Y and Zhao, Y and Feng, W and Yu, P and Li, S and Ding, Z},
title = {NRP1 silencing induces ROS-mediated cell cycle arrest and mitochondrial apoptosis in non-small cell lung cancer via upregulation of AGER.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {81},
number = {},
pages = {101080},
doi = {10.1016/j.clinsp.2026.101080},
pmid = {42579905},
issn = {1980-5322},
abstract = {OBJECTIVE: The specific role of Neuropilin-1 (NRP1) and its link to oxidative stress in Non-Small Cell Lung Cancer (NSCLC) progression remains unclear.

METHODS: Integrated bioinformatics, including weighted gene co-expression network analysis and machine learning, were applied to the TCGA cohort and validated in an age-stratified clinical cohort. In vitro assays evaluated proliferation, apoptosis, ATP, and Reactive Oxygen Species (ROS) in NRP1-silenced H1299 cells. Mechanisms were investigated using endogenous Co-Immunoprecipitation (Co-IP) and rescue experiments with AGER siRNA and the ROS scavenger N-Acetylcysteine (NAC).

RESULTS: Bioinformatics identified AGER as a key NRP1 downstream target. Clinically, NRP1 was significantly upregulated exclusively in elderly (≥65-years) NSCLC patients, whereas AGER was consistently downregulated. Functionally, NRP1 silencing inhibited proliferation, induced G1-phase arrest, and triggered mitochondria-dependent apoptosis characterized by severe ATP depletion and ROS accumulation. Endogenous Co-IP confirmed a direct physical interaction between NRP1 and AGER. Importantly, the oxidative stress and apoptotic phenotypes induced by NRP1 knockdown were effectively reversed by AGER silencing or NAC treatment.

CONCLUSION: The NRP1-AGER-ROS axis critically regulates tumor progression and oxidative stress in NSCLC, particularly in elderly patients, representing a promising age-associated therapeutic target.},
}

@article {pmid42580400,
year = {2026},
author = {Kowal, JL and Alam, S and Radhakrishnan, K and Dickmanns, A and Neumann, P and Schlotawa, L and Ficner, R and Dierks, T and Rudolph, MG and Niemann, HH},
title = {New structures of human formylglycine-generating enzyme reveal features important for catalysis, disease and structure-based drug design.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169987},
doi = {10.1016/j.jmb.2026.169987},
pmid = {42580400},
issn = {1089-8638},
abstract = {The formylglycine-generating enzyme (FGE) post-translationally modifies the active site of all human sulfatases. Mutations in the SUMF1 gene encoding FGE may lead to catalytically inactive FGE or destabilize the protein. The resulting lack of sulfatase modification causes the rare disease multiple sulfatase deficiency (MSD). Previously, FGE required elastase treatment for crystallization and the structures lacked copper, although FGE is a copper-dependent enzyme. Here, we show that highly active human FGE purified from insect cells natively contains one copper ion and we report six new crystal structures revealing previously unobserved features. Several structures contain the catalytic copper ion coordinated almost linearly by the two catalytic cysteines. A structure of the MSD-causing E130D variant shows distortions in coordination of a structural Ca[2+] explaining its lower stability. As part of exploratory ligand-soaking experiments, a structure of FGE soaked with N-acetyl cysteine methyl ester shows the binding of a small molecule to a site other than the active site highlighting a potential binding site to be explored in the development of pharmacological chaperones for FGE. Crystallization of FGE without elastase treatment resulted in a structure in which the previously missing loop is well defined in the electron density and partly covers the active site, indicating that it needs to adopt a different conformation for substrate binding. This assumption is supported by a second structure in which the loop faces away from the active site and leaves the substrate binding groove open and by the occasional occurrence of crystals in which the loop becomes disordered.},
}

@article {pmid42442476,
year = {2026},
author = {Namini, MRJ and Nielsen, PR and Gluud, M and Yan, L and Vadivel, CK and Zeng, Z and Hasselager, SS and Willerslev-Olsen, A and Ahmad, S and Sorrosal, LP and Geisler, C and Bonefeld, CM and Woetmann, A and Wang, CK and Gyrd-Hansen, M and Assaf, C and Becker, JC and Litman, T and Bzorek, M and Gjerdrum, LR and Lilla, S and Zanivan, S and Krejsgaard, T and Buus, TB and Ødum, N},
title = {Malignant T cells operate at the edge of redox tolerance and propagate oxidative stress in cutaneous T-cell lymphoma.},
journal = {The Journal of investigative dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jid.2026.07.003},
pmid = {42442476},
issn = {1523-1747},
abstract = {Reactive Oxygen Species (ROS) are tightly regulated in the skin and implicated in both cancer and inflammatory dermatoses, but the role of oxidative stress in cutaneous T-cell lymphoma remains largely unexplored. In this study, we aim to characterize oxidative stress and reduction-oxidation (redox) homeostasis in cutaneous T-cell lymphoma and determine whether increased ROS create a therapeutic vulnerability in malignant T cells and whether they affect neighboring keratinocytes. Lesional mycosis fungoides skin displays increased oxidative DNA and lipid membrane damage and a reduction-oxidation (redox) gene signature distinct from atopic dermatitis, characterized by SOD2 overexpression and PRDX2 repression-a rare redox profile confirmed at the protein level. Primary malignant T cells show widespread cysteine oxidation and constitutively elevated intracellular and mitochondrial ROS. Malignant T cells are selectively killed by 2,3-dimethoxy-1,4-naphthoquinone (and rescued by N-acetyl cysteine), demonstrating that they operate near their maximal antioxidant capacity. Romidepsin-induced apoptosis is similarly N-acetyl cysteine dependent. Supernatants from malignant (but not nonmalignant) T cells induce elevated ROS and recapitulate the SOD2-high/PRDX2-low signature in keratinocytes. This effect is amplified by Staphylococcus aureus activation. Taken together, we find that cutaneous T-cell lymphoma harbors a rare SOD2-high/PRDX2-low redox imbalance and that malignant T cells are sensitive to ROS induction but are able to propagate oxidative stress to keratinocytes.},
}

@article {pmid42566876,
year = {2026},
author = {Chen, X and Fan, X and Zhang, P and Qin, C and Li, K and Qin, B and Wang, J and Li, H and Xiao, Y},
title = {Palmatine chloride inhibits Microcystis aeruginosa via photosynthetic impairment, oxidative stress, and altered cellular energy status.},
journal = {Ecotoxicology and environmental safety},
volume = {323},
number = {},
pages = {120631},
doi = {10.1016/j.ecoenv.2026.120631},
pmid = {42566876},
issn = {1090-2414},
abstract = {Harmful cyanobacterial blooms threaten aquatic ecosystems and public health through cyanotoxin release and oxygen depletion. This study evaluated the inhibitory activity of palmatine chloride (PC) against Microcystis aeruginosa under different light and temperature conditions and investigated the associated physiological, biochemical, ultrastructural, and transcriptional responses. At 25°C, PC maintained concentration-dependent inhibition across 50-125 μmol·m[-2]·s[-1], achieving 48-52%, 92-96%, and 90-98% inhibition at 4, 8, and 12 mg/L, respectively, within seven days. At 35°C, 12 mg/L PC produced near-complete inhibition within 48 h. Specifically, PC markedly impaired photosynthetic performance, increased reactive oxygen species and malondialdehyde levels, altered antioxidant responses, and induced membrane disruption, thylakoid disorganization, and cytoplasmic leakage. N-acetylcysteine co-treatment did not restore growth or photosynthetic parameters, indicating that PC inhibition was not solely attributable to an NAC-reversible ROS-dependent process. Transcriptomic profiling and ATP measurements further indicated substantial disruption of cellular energy homeostasis, characterized by downregulation of genes involved in photosynthesis, respiration, and central carbon metabolism, together with an 84% decrease in intracellular ATP. Preliminary toxicity tests suggested relatively low acute toxicity to Daphnia magna and Vibrio fischeri under the tested conditions. Besides, PC had limited effects on Spirulina platensis but modestly inhibited Chlorella vulgaris, while no sustained accumulation of extracellular microcystin equivalents was detected. Collectively, PC strongly inhibited Microcystis aeruginosa, accompanied by photosynthetic impairment, oxidative stress, structural damage, and disruption of cellular energy homeostasis. These findings support further evaluation of PC as a candidate botanical algicide.},
}

@article {pmid42573610,
year = {2026},
author = {Misbah Ul Haq, M and Yousuf Khan, AK and Mohiuddin, M and Fareedullah, M},
title = {Paracetamol-induced hepatic injury following intentional self-poisoning: a case report and therapeutic considerations.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42573610},
issn = {1432-1912},
abstract = {Paracetamol (acetaminophen) overdose is a common cause of drug-induced hepatocellular injury and represents an important clinical emergency requiring timely evaluation and evidence-based management. N-acetylcysteine (NAC) remains the established antidote for preventing the progression of hepatic injury when administered promptly. We describe the case of an 18-year-old female who intentionally ingested eight tablets of paracetamol (650 mg each; total dose 5.2 g) and four tablets of cetirizine (10 mg each) following psychosocial distress. On presentation, she reported abdominal pain and had a history of transient altered consciousness prior to hospital arrival. Initial biochemical evaluation demonstrated mild hepatocellular injury, with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of 250 IU/L and 300 IU/L, respectively, while serum bilirubin and coagulation parameters (PT/INR) remained within normal limits, indicating the absence of acute liver failure. Following clinical assessment, the patient underwent gastric decontamination and received the standard intravenous NAC regimen, supportive therapy, serial monitoring of liver function, and comprehensive psychiatric evaluation. Liver enzyme concentrations progressively declined during hospitalization, reaching AST 60 IU/L and ALT 70 IU/L by day 3, with complete clinical recovery and no evidence of hepatic complications. Psychiatric assessment identified underlying psychosocial factors contributing to the intentional overdose, and appropriate pharmacological treatment and follow-up were initiated before discharge. This case demonstrates that favorable outcomes can be achieved through early risk assessment, guideline-directed NAC therapy, serial biochemical monitoring, and multidisciplinary management addressing both the toxicological and psychosocial aspects of intentional paracetamol overdose.},
}

@article {pmid42574880,
year = {2026},
author = {Zhu, H and Peng, W and Hu, L and Liu, Q and You, R and He, L and Zhao, Y and Yang, L},
title = {Super-resolution imaging with a mitochondria-targeted fluorescent probe: Evaluation of chemotherapy-induced hepatorenal injury.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {364},
number = {Pt 1},
pages = {128589},
doi = {10.1016/j.saa.2026.128589},
pmid = {42574880},
issn = {1873-3557},
abstract = {With the rising global incidence of cancer, anticancer drugs including cisplatin (DDP) and sunitinib (SU) are being widely used in clinical practice. However, severe nephrotoxicity of DDP and prominent hepatotoxicity of SU drastically restrict their clinical application. Therefore, real-time monitoring of liver and kidney function, along with early intervention of tissue damage progression, is essential during treatment. To address this challenge, we have herein developed a mitochondria-targeted super-resolution fluorescent probe ARP for hypochlorous acid (HClO). ARP's dual recognition sites and dual-signal detection ability significantly enhance its detection accuracy. Combined with super-resolution imaging technology, ARP elucidates the mechanism of ROS transformation induced by DDP and SU at the subcellular level. In vivo assays further validate the tissue-damage mechanisms of these two drugs and evaluate the protective effect of N-acetylcysteine (NAC) on the kidney and of silybin on the liver against drug-induced injury. The results demonstrate that both protective agents effectively alleviate hepatokidney damage without compromising the anti-tumor efficacy of the chemotherapeutic drugs. Hence, this work elucidates the anti-tumor and tissue injury mechanisms of DDP and SU in complex biological systems, providing a new strategy for mitigating drug-induced organ toxicity and offering a solid experimental basis for the rational design of clinical tumor chemotherapy regimens.},
}

@article {pmid42548070,
year = {2026},
author = {Li, H and Zhou, W and Liu, Y and Yan, Y and Wang, P and Li, A and Du, P},
title = {Identification of exopolysaccharides as the principal immunomodulatory components of Lactobacillus helveticus postbiotics and potential targets for quality control.},
journal = {Journal of the science of food and agriculture},
volume = {},
number = {},
pages = {},
doi = {10.1002/jsfa.70936},
pmid = {42548070},
issn = {1097-0010},
support = {JJ2025XQ0104//Heilongjiang Province Natural Science Foundation/ ; },
abstract = {BACKGROUND: As a novel immunomodulatory strategy alternative to live bacterial agents, postbiotics remain incompletely understood with respect to their principal functional components and mechanisms of action. This study isolated and identified the active ingredients - namely, exopolysaccharides (EPS) and bacteriocins - from the crude postbiotics (CP) of Lactobacillus helveticus KLDS 1.8701, and investigated their immunomodulatory and antioxidant properties and potential underlying mechanisms of action.

RESULTS: Characterization showed that the purified exopolysaccharide (PEPS) had a weight-average molecular weight of 134.6 kDa and an ordered triple-helical conformation. Functional comparison revealed that PEPS played a dominant role in bidirectional immunomodulation, significantly outperforming CP in promoting the proliferation of normal macrophages (viability reaching 230.61% at 5 mg mL[-1]) and inhibiting the abnormal proliferation of inflammatory cells (P < 0.05). Moreover, PEPS exhibited superior antioxidant capacity and significantly increased antioxidant enzyme activity in inflammatory cells (P < 0.05). In contrast, high concentrations of purified bacteriocin (PB) (> 1.25 mg mL[-1]) were cytotoxic, and its combination with PEPS did not yield a synergistic immunomodulatory effect. Intervention with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) further confirmed that PEPS inhibited the activation of the TLR4/NF-κB pathway by efficiently scavenging ROS. This anti-inflammatory effect was equivalent to that of the NAC group and significantly superior to that of the CP group (P < 0.05), whereas CP showed no compensatory effect via alternative pathways after ROS blockade.

CONCLUSION: This study identified and verified PEPS as the principal immunomodulatory component of the postbiotics of L. helveticus, providing a theoretical foundation for the development of standardized preparations using PEPS as a quality control target. © 2026 Society of Chemical Industry.},
}

@article {pmid42551764,
year = {2026},
author = {González-Blanco, L and Farrag, M and Sierra, V and Oliván, M and González-Gay, MA and Largo, R and Gantenbein, B and Pino, J and Farrag, Y and Gualillo, O},
title = {N-acetylcysteine regulates the endoplasmic reticulum stress response in CEP-like chondrocytes exposed to proinflammatory cytokines.},
journal = {Free radical biology & medicine},
volume = {255},
number = {},
pages = {650-658},
doi = {10.1016/j.freeradbiomed.2026.08.006},
pmid = {42551764},
issn = {1873-4596},
abstract = {BACKGROUND: Intervertebral disc degeneration (IVDD) is characterized by chronic inflammation and redox imbalance, which compromise cartilage endplate (CEP) cells and essential organelles such as the endoplasmic reticulum (ER), leading to protein misfolding and altered calcium homeostasis. To counteract this, cells activate the unfolded protein response (UPR) through the ATF6α, IRE1α, and PERK/eIF2α pathways. Due to its antioxidant properties, N-acetylcysteine (NAC) has been proposed as a modulator of these stress responses under proinflammatory conditions. However, the impact of NAC on IVDD remains poorly understood.

OBJECTIVE: This study aimed to analyse UPR signaling, calcium homeostasis, and ER stress-associated caspase activation in differentiated ATDC5 chondrocytes used as a CEP-like model under inflammatory stress, and to evaluate their modulation by NAC.

METHODS: Differentiated ATDC5 cells were exposed to IL-1α, IL-1β, and TNF (1 ng/mL) for 24 h in the presence or absence of NAC (100 μM). Oxidative status and ER stress-associated pathways were assessed using biochemical assays.

RESULTS: Proinflammatory cytokines induced redox imbalance, elevated cytosolic calcium levels, and upregulated HSP90. The ER stress response was intensified, as indicated by increased expression of IRE1α and ATF6α, along with increased caspase-12 expression under IL-1β stimulation, which is consistent with the activation of ER stress-associated caspase signaling. NAC treatment restored redox balance, normalized calcium levels and HSP90 expression, attenuated ATF6α activation, and reduced ER stress-associated caspase signaling.

CONCLUSIONS: NAC mitigates inflammation-induced oxidative and ER stress responses in CEP-like chondrocytes. These findings support redox-ER modulation as a potential strategy to preserve disc cell homeostasis during early IVDD and highlight NAC as a promising pharmacological approach to slow disease progression.},
}

@article {pmid42556747,
year = {2026},
author = {Venkitakrishnan, R and Vora, A and Thomas, PK and Bansal, A and Krishnan, S and Bansal, A and Nivangune, K and Panwala, R},
title = {Targeting chronic mucus hypersecretion in respiratory diseases - focus on OPEP devices.},
journal = {Respiratory medicine},
volume = {262},
number = {},
pages = {109085},
doi = {10.1016/j.rmed.2026.109085},
pmid = {42556747},
issn = {1532-3064},
abstract = {Chronic respiratory diseases pose an ever-increasing health burden in India. Chronic mucus hypersecretion (CMH) is a hallmark feature of many chronic obstructive respiratory diseases (CRDs). CMH is associated with impaired mucociliary clearance, recurrent infections, and disease progression. Effective airway clearance is therefore a key component of management. Several pharmacological and non-pharmacological strategies are used in CMH for clearing airways. Of these mucoactive drugs, N-acetylcysteine (NAC) and erdosteine are commonly used in India to manage CMH. Further, oscillating positive expiratory pressure (OPEP) devices have emerged as a non-pharmacological adjunct designed to enhance mucus clearance through the combined effects of positive expiratory pressure and oscillatory airflow. These mechanisms help stabilize airways, reduce mucus viscosity, and promote the mobilization of secretions toward the central airways for expectoration. Together, both mucoactive agents and OPEP devices prevent recurrent infections and exacerbations in chronic respiratory conditions and improve lung function and quality of life. The present review focuses on the prevalence of CMH in various CRDs, its impact on the natural history and disease progression in CRDs as well as various pharmacological and non-pharmacological therapies for CMH including published evidences. Special focus has been given to OPEP devices and therapeutic recommendations for practising clinicians have been provided.},
}

@article {pmid42543617,
year = {2026},
author = {Cai, Z and Chen, Y and Chen, L and Zhu, D},
title = {N-Acetylcysteine, Dichloroacetate, and Metformin Restore Mitochondrial Homeostasis by Counteracting Oxidative Stress and Fusion-Fission Imbalance in Palmitic Acid-Induced Lipotoxicity.},
journal = {Journal of oleo science},
volume = {75},
number = {8},
pages = {921-932},
doi = {10.5650/jos.ess25268},
pmid = {42543617},
issn = {1347-3352},
mesh = {*Palmitic Acid/toxicity/adverse effects ; *Oxidative Stress/drug effects ; *Metformin/pharmacology ; Animals ; *Acetylcysteine/pharmacology ; Reactive Oxygen Species/metabolism ; *Mitochondrial Dynamics/drug effects ; *Homeostasis/drug effects ; *Dichloroacetic Acid/pharmacology ; *Mitochondria/metabolism/drug effects ; Superoxide Dismutase/metabolism ; Mice ; GTP Phosphohydrolases/metabolism ; Glutathione Peroxidase/metabolism ; Catalase/metabolism ; Cell Line ; Dynamins/metabolism ; Muscle Fibers, Skeletal/metabolism ; },
abstract = {BACKGROUND: Palmitic acid (PA)-driven lipotoxicity in skeletal muscle is associated with excessive reactive oxygen species (ROS) and disturbed mitochondrial dynamics. This study aimed to characterize PA-induced alterations in oxidative status and fusion-fission balance in C2C12 skeletal muscle cells and to test whether N-acetylcysteine (NAC), dichloroacetate (DCA), or metformin mitigate these changes.

METHODS: Differentiated C2C12 myotubes were exposed to PA under conditions detailed in the Methods. Intracellular ROS was quantified, antioxidant defenses were assessed by activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and mitochondrial dynamics were evaluated by expression of the fusion protein mitofusin 1 (MFN1) and the fission protein dynamin-related protein 1 (DRP1), together with morphological assessment of mitochondrial fragmentation.

RESULTS: PA exposure increased ROS and was accompanied by decreases in CAT, GPx, and SOD activities. PA shifted mitochondrial dynamics toward fission, with reduced MFN1, elevated DRP1, and increased mitochondrial fragmentation. Co-treatment with NAC, DCA, or metformin attenuated PA-induced ROS accumulation, improved antioxidant enzyme activities relative to PA alone, and partially normalized MFN1 and DRP1 expression, with reduced fragmentation.

CONCLUSIONS: In an in vitro C2C12 model, PA-induced lipotoxicity is associated with oxidative stress and a fusion-fission imbalance favoring mitochondrial fragmentation. NAC, DCA, and metformin mitigate these alterations and help preserve mitochondrial homeostasis. These findings support targeting oxidative stress and mitochondrial dynamics as a potential approach to counteract mitochondrial dysfunction under lipotoxic conditions.},
}

*Palmitic Acid/toxicity/adverse effects
*Oxidative Stress/drug effects
*Metformin/pharmacology
Animals
*Acetylcysteine/pharmacology
Reactive Oxygen Species/metabolism
*Mitochondrial Dynamics/drug effects
*Homeostasis/drug effects
*Dichloroacetic Acid/pharmacology
*Mitochondria/metabolism/drug effects
Superoxide Dismutase/metabolism
Mice
GTP Phosphohydrolases/metabolism
Glutathione Peroxidase/metabolism
Catalase/metabolism
Cell Line
Dynamins/metabolism
Muscle Fibers, Skeletal/metabolism

@article {pmid42545402,
year = {2026},
author = {Gerini, E and Pompei, V and Cecati, M and Campagna, R and Pozzi, V and Filosa, A and Goteri, G and Salvolini, E and Emanuelli, M and Sartini, D},
title = {Upregulation of paraoxonase-2 enzyme in human osteosarcoma and its involvement in mechanisms promoting the aggressive behavior of tumor cells.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42545402},
issn = {1573-4978},
mesh = {Humans ; *Osteosarcoma/genetics/pathology/metabolism/enzymology ; *Aryldialkylphosphatase/genetics/metabolism ; Cell Line, Tumor ; *Bone Neoplasms/genetics/pathology/metabolism/enzymology ; Cell Proliferation/drug effects/genetics ; Apoptosis/drug effects/genetics ; Up-Regulation ; Gene Expression Regulation, Neoplastic ; Cell Movement/drug effects/genetics ; Female ; Reactive Oxygen Species/metabolism ; Male ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Glucose Transporter Type 1/metabolism ; },
abstract = {BACKGROUND: Osteosarcoma (OS) is the most common bone cancer, known for its aggressive nature, high chemoresistance, and strong metastatic potential responsible for poor clinical outcomes. In this context, identifying reliable biomarkers and therapeutic targets is therefore critical. This study investigates the role of paraoxonase-2 (PON2), an intracellular enzyme known for its anti-oxidative and anti-apoptotic properties. PON2 overexpression has been observed in various cancers and is implicated in tumor development and progression.

METHODS AND RESULTS: PON2 expression was evaluated by immunohistochemistry in bone tissue samples from OS patients and control subjects. shRNA-mediated PON2 silencing was performed in U-2 OS and Saos-2 cells to assess proliferation, viability, migration, chemosensitivity, ROS production, apoptosis activation, glucose uptake, and GLUT1 expression. PON2 overexpression and N-acetylcysteine (NAC) pre-treatment in CDDP-treated U-2 OS cells were used as rescue approaches. Preliminary analyses showed markedly higher PON2 expression in OS than in control bone specimens. PON2 knockdown reduced proliferation, viability, and migration, while enhancing sensitivity to cisplatin (U-2 OS and Saos-2) and doxorubicin (U-2 OS only); these effects were reversed by PON2 upregulation. PON2 silencing also increased ROS levels and caspase expression, and impaired glucose uptake by reducing GLUT1 expression and intracellular glucose levels. Since NAC did not fully rescue these alterations, PON2 appears to sustain chemoresistance by affecting important mechanisms related to ROS detoxification, glucose metabolism, and anti-apoptotic signaling.

CONCLUSIONS: Obtained data clearly illustrate the potential of PON2 as promising biomarker and molecular therapeutic target for human OS.},
}

Humans
*Osteosarcoma/genetics/pathology/metabolism/enzymology
*Aryldialkylphosphatase/genetics/metabolism
Cell Line, Tumor
*Bone Neoplasms/genetics/pathology/metabolism/enzymology
Cell Proliferation/drug effects/genetics
Apoptosis/drug effects/genetics
Up-Regulation
Gene Expression Regulation, Neoplastic
Cell Movement/drug effects/genetics
Female
Reactive Oxygen Species/metabolism
Male
Cell Survival/drug effects
Cisplatin/pharmacology
Doxorubicin/pharmacology
Drug Resistance, Neoplasm
Glucose Transporter Type 1/metabolism

@article {pmid42537761,
year = {2026},
author = {Campagnoli, LIM and Marchesi, N and Barbieri, A and Galeotti, N and Pascale, A},
title = {From antioxidant to senotherapeutic: Repurposing n-acetylcysteine to counteract senescence via the HuR pathway in human endothelial cells.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {113257},
doi = {10.1016/j.exger.2026.113257},
pmid = {42537761},
issn = {1873-6815},
abstract = {Cellular senescence plays a dual role in physiology and pathology. While it contributes to tumour suppression and tissue repair, its persistence promotes chronic inflammation, tissue dysfunction, and age-related diseases. Oxidative stress is a major driver of this process, and the RNA-binding protein HuR serves as a regulator by stabilizing transcripts encoding antioxidant and stress-response proteins. In this study, we established an in vitro model of replicative senescence using human umbilical vein endothelial cells (HUVECs) and investigated the potential anti-aging effects of N-acetylcysteine (NAC), an antioxidant and glutathione precursor. Late-passage HUVECs exhibited a senescent phenotype, including enlarged morphology, increased senescence-associated (SA)-β-galactosidase activity, elevated reactive oxygen species (ROS) levels, and upregulation of p16 and p21 proteins. We observed a progressive decline in HuR expression from early to late passages. NAC treatment counteracted these hallmarks, significantly decreasing ROS and p21 levels. Notably, NAC restored HuR expression and its protective targets, MnSOD and HSP70, and reduced inflammatory markers (IL-6 and TNF-α) levels. These findings suggest that the decline of the HuR-protective axis is a critical driver of endothelial senescence and demonstrate that NAC can mitigate aging hallmarks, representing a promising therapeutic strategy to target aging-related dysfunctions.},
}

@article {pmid42537248,
year = {2026},
author = {Ali, LS and Aladeeb, NM and Hamed, WHE and El-Hanafy, AA and Eldesoqui, M and Al-Wakeel, G},
title = {Effects of Ivabradine (If channel inhibitor) and N-Acetylcysteine against isoprenaline-induced myocardial injury: Role of Nrf2/HO-1 signaling and inflammation suppression.},
journal = {Tissue & cell},
volume = {104},
number = {Pt 1},
pages = {103806},
doi = {10.1016/j.tice.2026.103806},
pmid = {42537248},
issn = {1532-3072},
abstract = {Myocardial injury, induced experimentally using Isoprenaline (ISP), involves severe oxidative stress, inflammation, and cellular damage. The present study compared the cardioprotective effects of Ivabradine (IVB), an If channel antagonist, and N-Acetylcysteine (NAC), a glutathione precursor, against ISP-induced myocardial injury. Rats were divided into 5 groups (n = 8): Control (saline), ISP (150 mg/kg i.p. for 2 days), NAC (100 mg/kg/day oral for 14 days + ISP), IVB (5 mg/kg/day oral for 14 days + ISP), and NAC + IVB. Myocardial injury was assessed by measuring serum creatine kinase-myocardial band (CK-MB), cardiac troponin I (CTnI), and cardiac tissue levels of malondialdehyde (MDA) and Glutathione (GSH). qRT-PCR was performed for the expression of Interleukin-6 (IL-6), Nuclear factor erythroid-2 related factor 2 (Nrf2), and Haemoxygenase-1 (HO-1). Histopathological analysis and immunohistochemistry for Caspase-3 (apoptosis) and VEGF were performed. The ISP group showed markedly elevated CK-MB and CTnI, significant oxidative stress (highest MDA, lowest GSH), IL-6 upregulation, suppressed antioxidant defense (Nrf2/HO-1 downregulation), and extensive tissue damage (fibrosis, elevated Caspase-3). While single treatments offered significant protection, the co-administration of NAC and IVB demonstrated superior, synergistic efficacy. In conclusion, the combined therapy of NAC and IVB offers cardioprotection by maximally boosting the antioxidant defense system, suppressing inflammation, apoptosis, and fibrosis.},
}

@article {pmid42483932,
year = {2026},
author = {Mohanty, S and Suklabaidya, S and Mnatsakanyan, N and Jacobson, S and Harhaj, EW},
title = {HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-26},
doi = {10.1080/15548627.2026.2707897},
pmid = {42483932},
issn = {1554-8635},
abstract = {Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax regulatory protein plays a critical role in HTLV-1 persistence and pathogenesis; however, the underlying mechanisms are poorly understood. Here we show that Tax dynamically regulates mitochondrial reactive oxygen species (ROS) and membrane potential to trigger mitochondrial dysfunction. Tax is recruited to damaged mitochondria through its interaction with the IKK regulatory subunit IKBKG/NEMO and directly engages the ubiquitin-dependent PINK1-PRKN/parkin pathway to induce mitophagy. Tax also recruits autophagy receptors CALCOCO2/NDP52 and SQSTM1/p62 to damaged mitochondria to induce mitophagy. Furthermore, Tax requires PRKN to limit the extent of CGAS-STING1 activation and suppress type I interferon (IFN) induction. HTLV-1-transformed T-cell lines and PBMCs from HAM/TSP patients exhibit hallmarks of chronic mitophagy, and inhibition of PRKN in HTLV-1-transformed cell lines downregulates p19 Gag expression and induces cell death. Collectively, our findings suggest that Tax manipulation of the PINK1-PRKN mitophagy pathway represents a new HTLV-1 immune evasion strategy important for maintaining viral gene expression and cell survival.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; ATLL: adult T-cell leukemia/lymphoma; BafA1: bafilomycin A1; BECN1: beclin 1; CALCOCO2: calcium binding and coiled-coil domain 2; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CGAS: cyclic GMP-AMP synthase; co-IP: co-immunoprecipitation; DOX: doxycycline; GFP: green fluorescent protein; DNM1L/DRP1: dynamin 1 like; HAM/TSP: HTLV-1-associated myelopathy/tropical spastic paraparesis; HSPD1/HSP60: heat shock protein family D (Hsp60) member 1; HTLV-1: Human T-cell leukemia virus type 1; IFN: interferon; IkB: inhibitor of nuclear factor kappa B; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; IKK: IkB kinase; IRF3: interferon regulatory factor 3; KO: knockout; LAMP2: lysosome associated membrane protein 2; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MT-CO2: mitochondrially encoded cytochrome c oxidase II; mtDNA: mitochondrial DNA; mtROS: mitochondrial reactive oxygen species; NAC: N-acetylcysteine; NBR1: NBR1 autophagy cargo receptor; NFKB: nuclear factor kappa B; OPTN: optineurin; PBMCs: peripheral blood mononuclear cells; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; qRT-PCR: quantitative reverse transcription polymerase chain reaction; RFP: red fluorescence protein; ROS: reactive oxygen species; SAR: selective autophagy receptor; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TEM: transmission electron microscopy; TMRM: tetramethylrhodamine methyl ester; TOMM20: translocase of outer mitochondrial membrane 20; Ub: ubiquitin; VCL: vinculin; WT: wild-type.},
}

@article {pmid42534684,
year = {2026},
author = {Xu, M and Zhu, M and Zhao, WY and Li, Z and Xu, K and Yang, K and Wang, Z and Long, S and Zhang, Y and Cao, Y and Huang, S and Li, Z and Yu, G and Wang, L},
title = {Oregano extract induces apoptosis and inhibits autophagy in HepG2 cells via the PI3K/AKT pathway.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1884083},
pmid = {42534684},
issn = {1663-9812},
abstract = {Hepatocellular carcinoma (HCC) remains one of the most common and highly lethal malignancies globally. Conventional therapeutic approaches are often limited by suboptimal efficacy and significant toxicity, driving the search for alternative strategies, particularly those derived from natural products. This study aimed to evaluate the antitumor activity and underlying molecular mechanisms of the ethyl acetate extract of "Origanum vulgare" L (EAO) in human hepatocellular carcinoma cells. Our findings demonstrate that EAO markedly suppressed HepG2 and Huh7 cell proliferation and promoted apoptosis, accompanied by increased reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential, and ATP depletion. Additionally, EAO inhibited autophagy, as indicated by decreased LC3-II expression and increased p62 accumulation. Mechanistic investigations revealed that EAO inactivated the PI3K/AKT signaling pathway, and these effects were reversed by the ROS scavenger N-acetylcysteine (NAC), confirming ROS-dependent suppression of this pathway. Both network pharmacology and RNA-sequencing analyses further supported PI3K/AKT as a critical regulatory node. In summary, EAO exerts potent antitumor effects against hepatocellular carcinoma by inducing mitochondrial dysfunction and apoptosis, while concurrently suppressing autophagy through ROS-mediated inhibition of the PI3K/AKT pathway. These results highlight EAO as a promising low-toxicity candidate for the treatment of liver cancer.},
}

@article {pmid42537024,
year = {2026},
author = {Muhammad, MS and Isa, AS and Umar, AH and Bala, U and Oyedun, AR and Hassan, Z and John, P and Daniel, D and Faruk, F and Hassan, A and Buba, AS},
title = {Influence of Seasonal Variation on Anxiety-Like Behaviours in Albino Mice and the Modulatory Role of N-Acetyl Cysteine.},
journal = {Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria},
volume = {41},
number = {1},
pages = {63-74},
pmid = {42537024},
issn = {0794-859X},
mesh = {Animals ; *Acetylcysteine/pharmacology/therapeutic use ; Male ; Female ; *Anxiety/drug therapy/psychology ; Mice ; *Seasons ; *Behavior, Animal/drug effects ; Nigeria ; Maze Learning/drug effects ; Antioxidants/pharmacology ; },
abstract = {Anxiety disorders form one the most common type of mental illness and comprises of separation anxiety, specific phobias, social anxiety disorder, and generalized anxiety disorder. These disorders offer considerable comorbidity with other mental disorders like depression, memory and learning deficit which all shows considerable seasonal variance. Seasonal changes have major impact on health of individuals' especially mental health. N-Acetylcysteine (NAC) is an acetylated derivative of cysteine, and is considered as an antioxidant precursor to glutathione. It has been shown to ameliorate various types of mental disorders. This study investigated changes in anxiety-like behaviours in albino mice across different seasons in Nigeria and the modulatory role of NAC. The study was conducted across two seasons (cold dry and hot humid seasons) Nigeria. Forty (40) mice of both sexes (20/season) were used, divided into control (normal saline) and NAC (500mg/kg body weight) groups, respectively. All administration was done orally for one week and the rectal temperatures were measured. Behavioural test was conducted using Elevated Plus Maze (EPM) and Open Field Test under standard protocols for each season for a period of one week. The parameters for seasonal changes were also recorded. All analyses were done using Mixed ANOVA followed by Tukey's and Bonferroni's test, respectively and (P-values <0.05) were considered significant using SPSS version 22. The results of the study revealed a significant (P < 0.05) increase in anxiety-like behaviours in hot humid season and increased locomotive activity in cold dry season in male mice. Female mice were more susceptibility to anxiety in cold dry season, which was ameliorated by NAC. In conclusion, the study revealed that hot humid season have anxiogenic like effects, while cold dry season increased locomotive activities in male mice, demonstrating increase exploratory activity and decrease in level of anxiety. The study establishes the occurrence of anxiogenic-like behaviours in female mice in the cold dry season which was ameliorated by NAC administration. Key Words: Anxiety, Seasonal Variation, N-Acetyl Cysteine, Neurobehaviour Running Title: Seasonal variation and Anxiety-like behaviour.},
}

Animals
*Acetylcysteine/pharmacology/therapeutic use
Male
Female
*Anxiety/drug therapy/psychology
Mice
*Seasons
*Behavior, Animal/drug effects
Nigeria
Maze Learning/drug effects
Antioxidants/pharmacology

@article {pmid41780946,
year = {2026},
author = {Takeda, K and Ogata, K and Matsukawa, K and Yokokawa, H and Fukumoto, Y and Morimasa, K and Hidaka, T and Nogi, T and Watabe, K and Iijima, K and Nakamura, R and Ozawa, M and Kaneda, M},
title = {Effects of thiol compounds on DNA-damage detection and in vitro fertilization outcomes in bovine sperm.},
journal = {The Journal of reproduction and development},
volume = {72},
number = {4},
pages = {618-624},
doi = {10.1262/jrd.2025-138},
pmid = {41780946},
issn = {1348-4400},
mesh = {Animals ; Male ; Cattle ; *DNA Damage/drug effects ; *Fertilization in Vitro/veterinary ; *Spermatozoa/drug effects/metabolism ; Dithiothreitol/pharmacology ; *Sulfhydryl Compounds/pharmacology ; Acetylcysteine/pharmacology ; Female ; Cysteine/pharmacology ; In Situ Nick-End Labeling ; Glutathione/pharmacology ; Acrosome/drug effects ; Pregnancy ; },
abstract = {Reduced glutathione (GSH), a thiol compound, plays an important role in protecting sperm from excessive levels of reactive oxygen species. Our previous study demonstrated that GSH supplementation was associated with improved in vitro fertilization (IVF) outcomes. However, GSH supplementation also increased the proportion of DNA-damaged sperm detected in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, indicating involvement of its thiol components. In this study, we investigated the effects of several thiol compounds, including l-cysteine (Cys), N-acetyl-l-cysteine (NAC), and dithiothreitol (DTT), on bovine sperm DNA integrity. The addition of Cys or NAC (0.5, 1, or 5 mM) to the medium caused an increase in DNA damage, which was observed either throughout the sperm head or specifically in the post-acrosome (PA) region. DTT treatment increased DNA damage in both the PA and acrosomal regions, and it induced progressive sperm head lysis from the acrosome to the entire head. These treatments caused sperm DNA-damage rates that exceeded the normal range, suggesting that thiol groups enhance the detection of DNA damage. The effects of these thiols on IVF outcomes were further examined. Short-term exposure to 1 mM Cys before insemination improved cleavage rates, whereas prolonged exposure at concentrations ≥ 1 mM during insemination reduced cleavage rates. NAC supplementation had no significant effects. A mild negative correlation was observed between TUNEL-positive sperm rates and both cleavage and blastocyst formation rates following short-term treatment with 0.5 mM Cys. These findings suggest that thiol supplementation, when optimally dosed and timed, may enhance the sensitivity of DNA-damage detection rather than induce additional damage.},
}

Animals
Male
Cattle
*DNA Damage/drug effects
*Fertilization in Vitro/veterinary
*Spermatozoa/drug effects/metabolism
Dithiothreitol/pharmacology
*Sulfhydryl Compounds/pharmacology
Acetylcysteine/pharmacology
Female
Cysteine/pharmacology
In Situ Nick-End Labeling
Glutathione/pharmacology
Acrosome/drug effects
Pregnancy