@article {pmid41603285,
year = {2026},
author = {Karimi-Dehkordi, M and Saghaei, F and Saberian, M and Nejad, HS and Sohrabi, F and Zabihi, N},
title = {Feselol Ameliorates Acetaminophen-Induced Hepatotoxicity Through Multi-Pathway Modulation of Oxidative Stress, Inflammation, and Apoptosis in Mice.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {2},
pages = {e70710},
doi = {10.1002/jbt.70710},
pmid = {41603285},
issn = {1099-0461},
mesh = {Animals ; *Acetaminophen/adverse effects/toxicity ; *Oxidative Stress/drug effects ; Mice ; *Apoptosis/drug effects ; *Chemical and Drug Induced Liver Injury/metabolism/pathology/drug therapy/prevention & control ; Male ; *Inflammation/drug therapy/metabolism/chemically induced/pathology ; Liver/metabolism/pathology/drug effects ; },
abstract = {BACKGROUND AND AIM: Acetaminophen (APAP) overdose is a major cause of drug-related acute liver failure around the world. The limited treatment options beyond N-acetylcysteine (NAC) show a clear need for new liver-protective agents. Feselol, a natural compound known for its strong antioxidant effects, has become a potential candidate. This research aimed to evaluate feselol's anti-inflammatory, anti-apoptotic, and protective qualities against APAP-induced acute liver damage in a mouse model.

MATERIAL AND METHOD: The experiment included 42 mice divided into 7 groups, with some being administered a toxic dose of APAP only and others being given APAP in combination with 25 or 50 mg/kg of feselol. Serum levels of AST (serum aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), and GGT (gamma-glutamyl transferase) were examined. SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase) activities and MDA (malondialdehyde) levels were measured by colorimetric method. The liver tissue was analyzed through H&E staining. The expression of IL-1β, TNF-α, Bax, Caspase 3, and Bcl-2 genes was also examined by Real-time PCR.

RESULTS: The results showed that treatment of feselol at different doses with APAP led to a decrease in MDA levels to 23.25 nmol/mg (p < 0.05). Also, the activities of SOD, CAT and GPx enzymes in the group treated with a dose of 50 mg/kg of feselol with APAP were 33.09, 109.86, and 109.80, respectively, which was significant compared to the APAP group (p < 0.05). The results showed that simultaneous treatment with feselol and APAP resulted in a decrease in IL-1β and TNF-α gene expression by 1.67 and 1.015 fold, respectively (p < 0.05). Also, the expression of Bax (3.22-fold) and Caspase 3 (1.26-fold) genes decreased in the feselol-treated group and the expression of Bcl-2 (0.59-fold) gene increased. In the group that received APAP and feselol, the liver tissue was close to that of the control group. Feselol (50 mg/kg) coadministered with APAP significantly reduced ALT, AST, ALP, and GGP enzyme activity compared to the APAP-treated group (p < 0.05).

CONCLUSION: This study is notable for the discovery of feselol's pharmacological effects as a preventive drug against oxidative stress-associated hepatic impairment.},
}

Animals
*Acetaminophen/adverse effects/toxicity
*Oxidative Stress/drug effects
Mice
*Apoptosis/drug effects
*Chemical and Drug Induced Liver Injury/metabolism/pathology/drug therapy/prevention & control
Male
*Inflammation/drug therapy/metabolism/chemically induced/pathology
Liver/metabolism/pathology/drug effects

@article {pmid41602262,
year = {2025},
author = {Zacharia, GS and Ravte, V and Jyala, A and Shehi, E},
title = {Complementary and Alternative Medicine-Induced Combined Hepatorenal Toxicity: A Case Report.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100197},
pmid = {41602262},
issn = {2168-8184},
abstract = {Drug-induced liver injury (DILI) is a leading cause of liver disease globally, with complementary and alternative medicine (CAM) representing a significant contributor due to its widespread use and limited regulation. CAM encompasses diverse practices and products, with regional and ethnic diversity, many of which are used to treat liver disease. Even though a few natural remedies have been utilized for centuries, most lack scientific evidence for their safety and efficacy. This report describes a 42-year-old male who self-treated his fatty liver with CAM, culminating in severe concomitant hepatic and renal dysfunctions. Comprehensive evaluation excluded viral, autoimmune, metabolic liver diseases, and obstructive biliary diseases. The Roussel Uclaf Causality Assessment Method (RUCAM) score indicated a probable causal link between CAM and DILI of hepatocellular pattern. The constituents of the CAM, extracts of Carica papaya, Alstonia boonei, and Tetrapleura tetraptera, have been implicated in hepatotoxicity in animal models. Discontinuing the supplements and supportive care, including N-acetyl cysteine, led to symptomatic and biochemical improvement. This case highlights the importance of clinicians' awareness of CAM-related DILI, emphasizing the need for vigilance and patient education about the potential risks associated with herbal products.},
}

@article {pmid41602127,
year = {2025},
author = {Zeng, Q and Sun, Y and Lei, M and Liu, Z and Yan, X and Li, R and Zheng, J and Zha, J and Zhang, L and Guan, X and Yao, J},
title = {Nicotinic acid protects against hepatic ischemia-reperfusion injury via suppressing mitochondrial damage-induced ferroptosis.},
journal = {Liver research (Beijing, China)},
volume = {9},
number = {4},
pages = {324-337},
pmid = {41602127},
issn = {2542-5684},
abstract = {BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)-recognized for its antioxidative and metabolic regulatory properties-emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms.

METHODS: An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. N-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays.

RESULTS: NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI.

CONCLUSIONS: NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.},
}

@article {pmid41601049,
year = {2026},
author = {Firouzjaei, Y and Hajizadeh Moghaddam, A and Sohabatzadeh, F and Khanjani Jelodar, S and Farhadi, M},
title = {Neuroprotective effects of plasma-activated N-acetylcysteine against streptozotocin-induced behavioral deficits in rats: Attenuation of oxidative stress and cholinergic dysfunction.},
journal = {Ecotoxicology and environmental safety},
volume = {309},
number = {},
pages = {119619},
doi = {10.1016/j.ecoenv.2025.119619},
pmid = {41601049},
issn = {1090-2414},
mesh = {Animals ; *Acetylcysteine/pharmacology ; Male ; *Oxidative Stress/drug effects ; Rats ; *Neuroprotective Agents/pharmacology ; Streptozocin/toxicity ; Behavior, Animal/drug effects ; *Cognitive Dysfunction/chemically induced/drug therapy ; Plasma Gases ; },
abstract = {N-Acetylcysteine (NAC), a thiol-containing antioxidant, has demonstrated neuroprotective potential in various neurological disorders. Recently, cold atmospheric plasma (CAP) technology has emerged as a promising approach for modifying the physicochemical properties of biomolecules. This study investigated the neuroprotective effects of plasma-activated N-acetylcysteine (PAN) in a rat model of intracerebroventricular streptozotocin (icv-STZ)-induced cognitive impairment, with particular emphasis on redox homeostasis and cholinergic function. The physicochemical properties of PAN were characterized using FTIR, LC-MS/MS, and DPPH assay. Male rats received a single icv-STZ injection (3 mg/kg) on day 0, followed by oral administration of NAC or PAN (50 mg/kg) every other day for three weeks. Cognitive performance and anxiety-like behaviors were assessed using the shuttle box, novel object recognition, and elevated plus maze tests. Subsequently, oxidative stress indices (TAC, GSH, SOD, CAT, MDA, NO), cholinergic markers (AChE activity, ACh levels), and the expression of AChE, α7 nAChR, Nrf2, Keap1 and BDNF genes were quantified in the hippocampus and cerebral cortex. FTIR and LC-MS/MS analyses revealed plasma-induced chemical modifications in NAC, resulting in the generation of novel compounds. The DPPH assay further demonstrated superior radical scavenging activity of PAN compared with NAC. Behaviorally, PAN administration significantly alleviated STZ-induced cognitive deficits and anxiety-like behaviors. Biochemically, PAN normalized TAC, GSH, MDA, NO, and ACh levels, increased CAT and SOD activities, and reduced AChE activity. At the transcriptional level, PAN upregulated α7 nAChR, Nrf2 and BDNF expression while downregulating AChE and Keap1. Collectively, these findings suggest that PAN mitigates behavioral impairments in the icv-STZ rat model of Alzheimer's disease, potentially through attenuation of oxidative stress and restoration of cholinergic neurotransmission.},
}

Animals
*Acetylcysteine/pharmacology
Male
*Oxidative Stress/drug effects
Rats
*Neuroprotective Agents/pharmacology
Streptozocin/toxicity
Behavior, Animal/drug effects
*Cognitive Dysfunction/chemically induced/drug therapy
Plasma Gases

@article {pmid41597285,
year = {2026},
author = {Chung, YY and Kim, B and Lee, J and Kwak, S and Jung, M and Kim, YS and Baek, SK},
title = {Establishing a Non-Surgical Mouse Model of Laryngopharyngeal Reflux Disease: Acid-Induced Epithelial Disruption and Protective Role of N-Acetylcysteine.},
journal = {Cells},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/cells15020210},
pmid = {41597285},
issn = {2073-4409},
support = {2021R1F1A1056645 (RS-2021-NR063002)//National Research Foundation of Korea/ ; 2023R1A2C1004538 (RS-2023-NR076554)//National Research Foundation of Korea/ ; },
mesh = {Animals ; *Acetylcysteine/pharmacology/therapeutic use ; Female ; Disease Models, Animal ; Mice, Inbred C57BL ; *Laryngopharyngeal Reflux/pathology/drug therapy/metabolism ; Mice ; Cadherins/metabolism ; Matrix Metalloproteinase 7/metabolism ; *Acids ; Epithelial Cells/drug effects/pathology/metabolism ; *Protective Agents/pharmacology ; },
abstract = {Laryngopharyngeal reflux disease (LPRD) results from the retrograde flow of gastric contents into the upper aerodigestive tract, causing epithelial injury. Progress in its management has been limited by the lack of objective biomarkers and reproducible in vivo models. This study aimed to establish a chronic, non-surgical mouse model of LPRD and to investigate the protective effect of N-acetylcysteine (NAC). Female C57BL/6 mice were randomly assigned to three groups: control (standard drinking water), study (acidified water, pH 3.0, for 12 weeks), and treatment (acidified water for 12 weeks plus NAC supplementation during the final 4 weeks). Body weight, food intake, and water consumption were monitored weekly. Pharyngeal tissues were analyzed by immunohistochemistry and Western blotting. Chronic acid exposure resulted in loss of membrane-localized E-cadherin, cytoplasmic redistribution, and upregulation of matrix metalloproteinase-7 (MMP-7). These molecular alterations were accompanied by enhanced phosphorylation of ERK and c-Jun, consistent with activation of the ROS-ERK-c-Jun signaling pathway. NAC supplementation was associated with partial restoration of E-cadherin, reduced MMP-7 expression, and attenuation of ERK/c-Jun phosphorylation. No systemic toxicity or weight loss was observed, indicating good tolerability of the model. This non-surgical ingestion-based model faithfully recapitulates key epithelial features of LPRD and provides a feasible platform for mechanistic investigation and exploratory therapeutic studies. NAC may exert protective effects against acid-induced epithelial injury in this model.},
}

Animals
*Acetylcysteine/pharmacology/therapeutic use
Female
Disease Models, Animal
Mice, Inbred C57BL
*Laryngopharyngeal Reflux/pathology/drug therapy/metabolism
Mice
Cadherins/metabolism
Matrix Metalloproteinase 7/metabolism
*Acids
Epithelial Cells/drug effects/pathology/metabolism
*Protective Agents/pharmacology

@article {pmid41596085,
year = {2025},
author = {Chen, X and Gao, D and Wang, M and Wang, L and Hu, H and Wen, C and Tang, Y},
title = {Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: Pathogenic Mechanisms, Crosstalk with Oxidative Stress, and Antioxidant Therapeutic Potential.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/antiox15010025},
pmid = {41596085},
issn = {2076-3921},
support = {82305145//National Natural Science Foundation of China/ ; LQ23H270006//Zhejiang Provincial Natural Science Foundation of China/ ; },
abstract = {Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and the formation of immune complexes (ICs), which lead to widespread inflammation and tissue damage. Neutrophil extracellular traps (NETs), web-like structures composed of DNA, histones, and antimicrobial proteins released by activated neutrophils, play a crucial role in innate immunity by defending against pathogens. However, excessive NET formation and ineffective clearance of these structures contribute to the development of SLE. This review explores the mechanisms behind NET formation in SLE, their relationship with oxidative stress, and the potential role of antioxidants in treatment. Research indicates that SLE patients exhibit two key abnormalities: excessive NET formation and impaired NET clearance. Excessive NET formation is driven by proinflammatory low-density granulocytes (LDGs) and immune complexes (ICs). Impaired NET clearance stems from reduced DNase1/DNase1L3 activity or anti-nuclease autoantibodies. These two abnormalities lead to elevated circulating NETs. These NETs act as autoantigen reservoirs, forming pathogenic NET-ICs that amplify autoimmune responses. Oxidative stress drives NET formation by activating NADPH oxidase. In contrast, various antioxidants, including enzymatic and non-enzymatic types, can inhibit NET formation via scavenging reactive oxygen species (ROS) and blocking NADPH oxidase activation. Preclinical studies show that antioxidants such as curcumin, resveratrol, and mitochondrial-targeted MitoQ reduce NET formation and ameliorate lupus nephritis; clinical trials confirm that curcumin and N-acetylcysteine (NAC) lower SLE disease activity and reduce proteinuria, supporting their role as safe adjuvant therapies. However, high-dose vitamin E may exacerbate autoimmunity, highlighting the need for dose optimization. Future research should aim to clarify the mechanisms underlying NET formation in SLE and to optimize new antioxidant therapies, including assessments of their long-term efficacy and safety.},
}

@article {pmid41595622,
year = {2025},
author = {Dinç, M and Bayrak, HÇ and Karasu, R and Aykaç, B and Soydemir, ÖC and Saricetin, A},
title = {Intra-Articular N-Acetylcysteine Reduces Synovitis Without Preventing Cartilage Degeneration in Experimental Osteoarthritis.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/biomedicines14010086},
pmid = {41595622},
issn = {2227-9059},
abstract = {Background/Objectives: Osteoarthritis (OA) is a multifactorial degenerative joint disease characterized by synovial inflammation, oxidative stress, and progressive cartilage degeneration. This study investigated whether intra-articular N-acetylcysteine (NAC) attenuates synovial inflammation and oxidative stress and whether these effects translate into structural cartilage protection. Methods: OA was induced in rats by anterior cruciate ligament transection (ACLT). NAC (5 mg/50 µL) was administered intra-articularly once weekly for three weeks post-ACLT. Inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (iNOS, TAS, TOS, OSI), and cartilage degradation markers (MMP-13, COMP, CTX-II) were quantified in synovial fluid and cartilage homogenates using ELISA. Cartilage integrity was evaluated histologically using the modified Mankin scoring system. Results: Compared with controls, NAC significantly reduced synovial IL-1β, IL-6, TNF-α, MMP-13, and iNOS levels and improved the synovial redox profile by increasing TAS and reducing TOS and OSI (all p < 0.05). In contrast, NAC did not significantly alter cartilage homogenate levels of inflammatory cytokines, oxidative stress indices, or degradation markers (COMP, CTX-II, MMP-13). Histological analysis demonstrated persistent cartilage fissuring, hypocellularity, and proteoglycan loss in both groups (p > 0.05). Conclusions: Intra-articular NAC exerts potent anti-inflammatory and antioxidative effects within the synovial compartment but fails to prevent cartilage degeneration in the ACLT model. These findings indicate a compartment-specific therapeutic profile, suggesting that NAC may function as a symptom-modifying agent in synovitis-dominant OA rather than a structure-modifying therapy. Future studies should focus on optimized delivery systems or combination strategies targeting cartilage and subchondral bone to achieve disease modification.},
}

@article {pmid41593161,
year = {2026},
author = {Ozhan, O and Ekici, C and Ates, B and Yildiz, A and Balcioglu, S and Vardi, N and Parlakpinar, H},
title = {N-acetyl cysteine amide mitigates oxidative stress and apoptosis in a rat model of renal ischemia-reperfusion injury.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-37274-8},
pmid = {41593161},
issn = {2045-2322},
support = {2209a//Türkiye Bilimsel ve Teknolojik Araştırma Kurumu/ ; },
}

@article {pmid41593024,
year = {2026},
author = {Chen, Z and Zhang, X and Li, J and Feng, C and Xiong, Y and Yan, L},
title = {Facile Synthesis of Thioketal-Functionalized Poly(amino acid) Nanocarriers for ROS-Triggered Drug Release in Cancer Therapy.},
journal = {ACS macro letters},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsmacrolett.5c00731},
pmid = {41593024},
issn = {2161-1653},
abstract = {Polymer nanocarriers offer significant advantages in antitumor drug delivery; however, achieving a balance between minimizing nonspecific drug release in blood circulation and maximizing specific intracellular drug release remains a critical challenge. To address this, this study developed a cross-linked poly(amino acid) nanocarrier sensitive to intracellular reactive oxygen species (ROS). A novel thioketal-functionalized, ROS-sensitive bicyclic amino acid N-carboxyanhydride (NCA) monomer was designed and synthesized, and ROS-responsive poly(amino acid)s were prepared via ring-opening polymerization. Polymeric nanomicelles loaded with doxorubicin (DOX) were successfully fabricated using a microemulsion method, and their ROS-responsive properties were systematically evaluated. In vitro release experiments demonstrated that the nanocarrier exhibited H2O2 concentration-dependent, ROS-triggered drug release characteristics. The oxidative response behavior of the drug-loaded nanomicelles was further validated in cellular and animal models by introducing the ROS scavenger N-acetylcysteine (NAC). In a 4T1 tumor-bearing mouse model, these drug-loaded nanomicelles showed enhanced tumor retention and superior tumor suppression compared to free DOX. This study demonstrates that thioketal-functionalized poly(amino acid) nanocarriers hold promise in balancing blood circulation stability and intracellular specific drug release, providing a novel design strategy for developing efficient and safe poly(amino acid)-based anticancer nanomedicines.},
}

@article {pmid41586115,
year = {2025},
author = {Jafarzadeh, E and Pashaei-Asl, R and Hakimi, P and Pashaiasl, M},
title = {The Effect of Letrozole and N-Acetylcysteine on the Expression Levels of Genes Involved in Glucose Metabolism in Patients with Polycystic Ovary Syndrome: A Clinical Trial Study.},
journal = {Journal of reproduction & infertility},
volume = {26},
number = {2},
pages = {81-89},
pmid = {41586115},
issn = {2228-5482},
abstract = {BACKGROUND: N-acetylcysteine (NAC) is a supplement commonly used in patients with polycystic ovary syndrome (PCOS). The expansion of oocyte-associated cumulus cells (CCs) and the quality of the oocyte are critical factors influencing fertilization rates and clinical pregnancy outcomes in assisted reproductive techniques (ARTs). Genes such as phosphofructokinase (PFKP) and pyruvate kinase isoform M2 (PKM2) are involved in glucose metabolism and are crucial in the regulation of oocyte competence and developmental potential. The purpose of the current study was to evaluate the effects of letrozole and NAC on the expression of PFKP and PKM2 in CCs of PCOS patients undergoing ART.

METHODS: The study evaluated 20 PCOS women undergoing ART to assess the effect of letrozole and NAC on the expression levels of PKM2 and PFKP genes in cumulus cells. Women were randomly assigned using a simple randomization method into four groups: control, NAC, letrozole, and NAC plus letrozole, with five women in each group. Gene expression levels of PKM2 and PFKP were measured using real-time PCR.

RESULTS: The expression level of PKM2 was significantly higher in the letrozole plus NAC group compared to the control group (p<0.05). In NAC group, PFKP was significantly expressed compared to the control group (p<0.05). There were no significant differences among the other groups compared to the control group.

CONCLUSION: NAC can improve the quality of oocytes by increasing the expression level of genes involved in the glucose metabolism (PKM2, PFKP) of CCs, thereby potentially improving ART success rate in PCOS patients. Therefore, administering NAC along with letrozole can have a synergistic effect on increasing the expression level of genes associated with blastocyst quality in PCOS patients.},
}

@article {pmid41582130,
year = {2026},
author = {Li, C and Yuan, Y and Bao, Y and Ni, Y and Chen, N and Piao, J and Wang, L and Zhu, Z},
title = {Synergistic regulation of TGF-β1/Smad2/3 signaling and inflammatory pathways via SA/NAC-based nanoplatforms: a novel strategy to enhance anti-fibrotic therapeutic outcomes in idiopathic pulmonary fibrosis.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04071-4},
pmid = {41582130},
issn = {1477-3155},
support = {LQ20H270014//National Natural Science Foundation of Zhejiang Province/ ; LY23H280010//Zhejiang Provincial Natural Science Foundation of China/ ; 2023JKZKTS23//Research Project of Zhejiang Chinese Medical University/ ; },
abstract = {Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by progressive fibrosis and poor prognosis, with no current therapies capable of reversing the fibrotic changes. The aberrant repair driven by fibroblast activation and an inflammatory microenvironment results in irreversible IPF. In this work, a macrophage-derived apoptotic body delivery system (SA + NAC@AB) co-loaded with sodium arsenite (SA) and N-acetylcysteine (NAC) was developed to exert synergistic antifibrotic activity against IPF via coordinated regulation of TGF-β1 signaling and inflammation. Apoptotic bodies derived from macrophages inherit inflammation-homing capability, enabling targeted delivery to fibrotic lesions. In vivo evaluation in a bleomycin-induced IPF mouse model demonstrated that SA + NAC@AB effectively targeted the lungs, significantly improved body weight and survival, and alleviated pulmonary fibrosis. Immunofluorescence and Western blot analyzes revealed that SA + NAC@AB reduced Smad2/3 phosphorylation and M2 macrophage polarization, indicating regulation of the TGF-β1/Smad2/3 pathway and inflammation as part of its mechanism of action. Furthermore, in vitro studies validated the enhanced efficacy of SA + NAC@AB, which significantly promoted fibroblast uptake, thereby potentiating its inhibitory effects on fibroblast viability, as well as TGF-β1-induced migration and differentiation. In conclusion, our study demonstrates that SA + NAC@AB represents an effective therapeutic strategy for IPF, offering a promising novel approach by modulating both the TGF-β1/Smad2/3 signaling pathway and the inflammatory response.},
}

@article {pmid41579736,
year = {2026},
author = {Mah, E and Gallagher, D and Gao, F and Ramirez, J and Rabin, JS and Survilla, K and Vieira, D and Chen, JJ and Kang, Y and Andreazza, A and Herrmann, N and Kiss, A and Marzolini, S and Oh, P and Swardfager, W and Black, SE and Lanctôt, KL},
title = {Frontal white matter hyperintensity burden predicts cognitive response to N-acetylcysteine and exercise in vascular mild cognitive impairment.},
journal = {Neurobiology of aging},
volume = {161},
number = {},
pages = {39-46},
doi = {10.1016/j.neurobiolaging.2026.01.005},
pmid = {41579736},
issn = {1558-1497},
abstract = {Vascular mild cognitive impairment (vaMCI) is a prodromal stage of dementia defined by cognitive deficits due to cerebrovascular disease. Increased white matter hyperintensity (WMH) volume has been associated with reduced executive function (EF). We explored whether lower baseline frontal and global WMH volume predicted an improvement in EF in vaMCI participants treated with N-acetylcysteine (NAC) and exercise as compared to placebo and exercise. Fifty-eight individuals with vaMCI received exercise therapy and were randomized to NAC or placebo. EF was assessed using the Trail Making Test Part B (TMT-B), Digit Symbol-Coding Test (DSCT), and a test of phonemic fluency, at baseline, 3 months, and 6 months. WMH volumes were measured from baseline magnetic resonance imaging scans. Linear mixed models were used. All participants improved on TMT-B (β = -0.185, SE = 0.046, p < 0.001) and phonemic fluency (β = 4.440, SE = 0.911, p < 0.001) over 6 months. A significant three-way interaction between baseline frontal WMH volume, treatment group, and timepoint predicted TMT-B performance at 3 months (β = 0.160, SE = 0.076, p = 0.039), but not at 6 months. No significant interactions were found for DSCT or phonemic fluency. Global WMH did not predict treatment response. Participants demonstrated improvement in EF regardless of treatment group and WMH volume. Lower frontal WMH volume predicted a greater improvement in TMT-B performance at 3 months in those treated with NAC versus placebo. These findings underscore the importance of considering participant heterogeneity in trials for vaMCI.},
}

@article {pmid41579706,
year = {2026},
author = {Madhavan, A and Schiano-Visconte, M and Dutton, L and Cantalupo, M and Balasco, L and Mavillonio, A and Chelini, G and Bozzi, Y and Pangrazzi, L},
title = {Astaxanthin improves behavioural and immune dysfunction in the Shank3b mouse model of autism spectrum disorder.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {195},
number = {},
pages = {119051},
doi = {10.1016/j.biopha.2026.119051},
pmid = {41579706},
issn = {1950-6007},
abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviours. Numerous studies have associated ASD with immune dysregulation and inflammation, with neuroinflammatory processes reported in ASD individuals and mouse models. Altered immune cell profiles and cytokine levels have been observed in the peripheral blood (PB), supporting systemic immune dysfunction. Recently we showed that the administration of antioxidant molecule N-acetylcysteine (NAC) reduced oxidative stress and inflammation and counteracted behavioural deficits in two mouse models of ASD, providing a rationale for exploring other redox-active compounds. Here, we investigated the effects of astaxanthin (AST), potent antioxidant and anti-inflammatory molecule, in the Shank3b model (Shank3b[-/-] mice). AST treatment significantly improved core ASD-like behaviours, including social interaction deficits, motor incoordination, and repetitive grooming. In the cerebellum, AST reduced pro-inflammatory cytokines and counteracted microglial hyperactivation. In peripheral immune compartments, AST modulated cytokine expression. Pro-inflammatory markers were downregulated in Shank3b[-/-] mice in the bone marrow and spleen while they were elevated in Shank3b controls, suggesting immune rebalancing (i.e. adaptive modulation suppressing harmful inflammation while supporting protective immunity). As a limitation, oxidative stress assays were not performed here. Receiver operating characteristic (ROC) analysis suggests that TNF and IFNγ expression in peripheral immune cells may be promising biomarkers of treatment response. Notably, unlike NAC, AST did not induce pro-inflammatory effects in Shank3b[+/+] animals. These findings show that AST administration may counteract behavioural deficits and immune dysfunction in Shank3b[-/-] mice, therefore suggesting its potential as a safe immunomodulatory therapy for ASD.},
}

@article {pmid41577060,
year = {2026},
author = {Abdeltawab, M and Ebid, AH and Ahmed, O and Mobarez, MA and Ibrahim, M},
title = {N-acetylcysteine Reduces Incidence and Duration of Linezolid-Associated Thrombocytopenia in Critically Ill Patients: A Randomized Controlled Trial.},
journal = {Environmental toxicology and pharmacology},
volume = {},
number = {},
pages = {104944},
doi = {10.1016/j.etap.2026.104944},
pmid = {41577060},
issn = {1872-7077},
abstract = {Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥48hours. Patients received IV NAC (600mg every 12hours) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10[3]/mm[3] or >50% reduction from baseline). NAC significantly reduced LAT incidence (16.8% vs. 41.6%; p < 0.001), platelet transfusions (1.6% vs. 11.2%; p = 0.003), and linezolid discontinuations (6.4% vs. 32.0%; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT05944458. Registered on July 6, 2023.},
}

@article {pmid41575655,
year = {2026},
author = {Li, B and Liu, P and Yang, X and Li, M and Lei, L and Meng, Z and Song, Y and Lan, J and Ouyang, C and Ma, J and Liu, Q},
title = {NAC and DNase I synergistically reduce NETs to attenuate severe acute pancreatitis via suppressing the NETs/NF-κB/CXCL3 pathway.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {31},
number = {2},
pages = {58},
pmid = {41575655},
issn = {1573-675X},
mesh = {*Deoxyribonuclease I/pharmacology/therapeutic use ; *Extracellular Traps/drug effects/metabolism ; *NF-kappa B/metabolism/genetics ; Animals ; *Acetylcysteine/pharmacology/therapeutic use ; *Pancreatitis/drug therapy/metabolism/pathology ; Mice ; Signal Transduction/drug effects ; Male ; Humans ; Neutrophils/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; Mice, Inbred C57BL ; Apoptosis/drug effects ; Oxidative Stress/drug effects ; },
abstract = {Neutrophil extracellular traps (NETs) drive severe acute pancreatitis (SAP) progression by promoting pancreatic injury, duct obstruction, and systemic inflammation. Reactive oxygen species (ROS) are critical for NETs formation, while NETs degradation remains therapeutically challenging. This study investigates whether combined N-acetylcysteine (NAC) and deoxyribonuclease I (DNase I) therapy mitigates SAP and associated lung injury by suppressing NETs formation and degradation, respectively, and explores the underlying molecular mechanisms. NETs were elevated in SAP pancreatic tissue. In vitro, NAC reduced NETs formation by inhibiting oxidative stress, while DNase I degraded preformed NETs. Combined therapy surpassed monotherapy efficacy, synergistically attenuating NETs burden. In vivo, Early dual intervention degraded NETs, reduced neutrophil infiltration and apoptosis, and lowered inflammatory cytokines, thereby alleviating pancreatitis and lung injury. Mechanistically, dual therapy suppressed NF-κB activation in pancreatic tissue, decreasing CXCL3 release and subsequent CXCR2-positive neutrophil recruitment, ultimately ameliorating SAP. NAC and DNase I synergistically target NETs generation and clearance, offering a promising redox-based therapeutic strategy for SAP.},
}

*Deoxyribonuclease I/pharmacology/therapeutic use
*Extracellular Traps/drug effects/metabolism
*NF-kappa B/metabolism/genetics
Animals
*Acetylcysteine/pharmacology/therapeutic use
*Pancreatitis/drug therapy/metabolism/pathology
Mice
Signal Transduction/drug effects
Male
Humans
Neutrophils/drug effects/metabolism
Reactive Oxygen Species/metabolism
Mice, Inbred C57BL
Apoptosis/drug effects
Oxidative Stress/drug effects

@article {pmid41574386,
year = {2026},
author = {Yadav, N and Singh, R and Mondal, SK and Mandal, AK},
title = {Molecular Insights of p-Benzoquinone-Induced Red Blood Cell Dysfunction: Probable Implications to Cigarette Smoke-Associated Pathologies.},
journal = {Free radical research},
volume = {},
number = {},
pages = {1-26},
doi = {10.1080/10715762.2026.2620638},
pmid = {41574386},
issn = {1029-2470},
abstract = {Cigarette smoke (CS) is a complex mixture of numerous chemicals, including p-benzosemiquinone (pBSQ), which oxidizes to p-benzoquinone (pBQ) in the lungs of smokers and enters circulation. Despite its high reactivity, the direct impact of pBQ on human red blood cells (RBC) remains underexplored. Herein, we investigated the molecular insights into how pBQ compromises human RBC physiology and its role in mediating CS-associated pathologies by integrating redox biochemistry, membrane integrity, and omics-based approaches. Our findings reveal that pBQ disrupted redox homeostasis, evidenced by glutathione depletion, elevated reactive oxygen species, lipid peroxidation, and reduced antioxidant enzyme activity. pBQ also triggered methemoglobin formation, hemoglobin aggregation, and reduced oxygen-binding capacity. Biophysical analysis of RBCs revealed reduced membrane fluidity, alterations in membrane proteins and lipids, disrupted zeta potential, and sedimentation dynamics, suggesting altered deformability, an indication of impaired microvascular transit. Untargeted metabolomics and lipidomics profiling revealed metabolic reprogramming and remodelling of the membrane lipids. Depletion of polyunsaturated fatty acids alongside accumulation of saturated species in the membrane points towards membrane stiffening. Pathway analysis highlighted perturbations in fatty acid biosynthesis and redox homeostasis. Disease enrichment analysis linked these changes to hypertension and other pathologies that are previously linked to redox imbalance and CS exposure. Notably, NAC co-treatment mitigated these effects, preserving RBC integrity and redox homeostasis. These findings underscore that pBQ is a critical mediator of CS-induced RBC dysfunction and establish a mechanistic link to its contribution to smoking-associated complications.},
}

@article {pmid41563857,
year = {2026},
author = {Race, NS and Uchida, K and Burcham, PC and Shi, R},
title = {Multimodal Toxicity of Acrolein and Associated Therapeutic Strategies in Central Nervous System Trauma and Disease.},
journal = {Annual review of biomedical engineering},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-bioeng-103023-035352},
pmid = {41563857},
issn = {1545-4274},
abstract = {Acrolein is a highly reactive α,β-unsaturated aldehyde produced endogenously through lipid peroxidation and enzymatic metabolism and exogenously via environmental exposures. Acrolein covalently adducts to DNA and proteins, leading to oxidative stress, mitochondrial dysfunction, and inflammation, including innate immune response activation via natural antibodies. Acrolein is difficult to measure in biological systems, but acrolein-bound covalent products can be measured reliably. Therapeutically, nucleophilic small molecules that scavenge acrolein such as hydralazine, phenelzine, dimercaprol, carnosine, and N-acetylcysteine (NAC) have shown neuroprotective effects in animal models of multiple sclerosis, Parkinson's disease, spinal cord injury, and traumatic brain injury. These effects include preserved membrane and mitochondrial integrity, reduced inflammation, reduced pain, and improved motor, sensory, and cognitive outcomes. Alternative strategies that enhance clearance or inhibit production of acrolein show promise but face limitations. Acrolein is a key pathophysiological mediator and a viable therapeutic target in central nervous system trauma and neurodegenerative diseases.},
}

@article {pmid41562319,
year = {2026},
author = {Hossen, F and Kouwaki, T and Fujiwara, Y and Tsutsuki, H and Zhang, T and Guo, C and Rahman, A and Komohara, Y and Oshiumi, H and Sawa, T},
title = {Therapeutic Efficacy of the Supersulfide Donor NAC-S2 in Influenza Virus Pneumonia via Suppression of Excessive Inflammatory Responses.},
journal = {Microbiology and immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1348-0421.70039},
pmid = {41562319},
issn = {1348-0421},
support = {21H05267//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 21H05258//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 25H01029//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 25K02477//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 23K06362//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 23K07942//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 25K22315//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; 23gm161001h001//Japan Agency for Medical Research and Development/ ; },
abstract = {Influenza pneumonia is characterized by excessive inflammatory responses that contribute to severe lung injury and mortality. Supersulfides, endogenously produced cysteine-derived persulfides and polysulfides, exert potent antioxidant, anti-ferroptotic, and anti-inflammatory activities; however, their therapeutic potential after disease onset remains unclear. Here, we investigated the efficacy of N-acetylcysteine tetrasulfide (NAC-S2), a highly water-soluble and cell-permeable supersulfide donor, in a mouse model of influenza A virus (IAV)-induced pneumonia. Subcutaneous administration of NAC-S2 rapidly elevated systemic levels of cysteine- and glutathione-derived supersulfides. In therapeutic treatment starting 2 days post-infection, when body weight loss and clinical signs had already developed, NAC-S2 significantly improved survival and mitigated body weight loss compared with vehicle and oxidized NAC controls. Metabolomic analysis revealed that influenza virus infection depleted lung glutathione persulfide (GSSH), while NAC-S2 effectively restored tissue GSSH levels. NAC-S2 treatment markedly reduced pulmonary interleukin (IL)-1β and IL-6 production without affecting viral load or Type-I interferon responses. Furthermore, NAC-S2 suppressed NLRP3 inflammasome activation and gasdermin D expression, leading to decreased infiltration of CD3[+] T cells and myeloperoxidase-positive neutrophils. Histopathological analyses confirmed that NAC-S2 ameliorated epithelial injury, interstitial edema, and hemorrhage in infected lungs. Collectively, our findings demonstrate that NAC-S2 exerts therapeutic benefit even after the onset of severe influenza pneumonia, primarily by replenishing supersulfides and alleviating excessive inflammatory responses. Supersulfide donors represent a promising class of adjunctive therapeutics for severe viral pneumonia.},
}

@article {pmid41558638,
year = {2026},
author = {Moseanko, A and Ginwalla, C and Eidman, M and Dash, S and Lewis, J and Albertson, TE},
title = {Pediatric Intravenous Acetaminophen Overdoses: A Continuing Iatrogenic Problem.},
journal = {Hospital pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1542/hpeds.2025-008624},
pmid = {41558638},
issn = {2154-1671},
abstract = {OBJECTIVE: To determine if intravenous (IV) acetaminophen use in children remains a source of iatrogenic overdosing.

METHODS: A cluster of 3 index cases in early 2025 stimulated a 14-year (2011-2024) retrospective study of calls from health care facilities to the California Poison Control System (CPCS) involving IV acetaminophen dosing errors in children aged 16 years or younger. All calls during this period that involved pediatric IV acetaminophen were reviewed and data abstracted. Date of call, age of child, location in the hospital, laboratory results, acetaminophen levels, intended dose, dose given, use of N-acetylcysteine (NAC), and outcomes were recorded. Descriptive statistics were used.

RESULTS: The 3 index pediatric cases of IV acetaminophen overdose ranged from 3 to 10 times the desired dose. Two of the 3 patients were treated with NAC. The retrospective review of CPCS calls resulted in 42 additional cases in which intravenous dosing errors occurred with mean doses of 45.5 ± 36.7 mg/kg (range, 14.7-147.1 mg/kg) and mean age of 4.9 years ± 4.0 (1 day to 16 years). Two additional patients were treated with NAC. These adverse events happened in operative/perioperative areas (13 cases), 11 cases on the pediatric inpatient units, 5 in intensive care units, 12 in the emergency department, and 4 in unknown areas. No long-term adverse effects were seen in the 45 children.

CONCLUSION: Rare pediatric iatrogenic IV acetaminophen overdoses continue to be seen in acute care settings. Determining potential toxicity and the need for NAC remains challenging. Further efforts are needed to prevent this infrequent serious medication error.},
}

@article {pmid41558404,
year = {2026},
author = {Aral, H and Aral, T and Sunkur, M and Çolak, M and Bağcık, M},
title = {N-acetylcysteine-functionalised a multimodal HPLC stationary phase for broad-range separations.},
journal = {Talanta},
volume = {302},
number = {},
pages = {129397},
doi = {10.1016/j.talanta.2026.129397},
pmid = {41558404},
issn = {1873-3573},
abstract = {In this study, a new multimodal HPLC stationary phase derived from N-acetyl-l-cysteine was synthesized and comprehensively evaluated across a broad polarity spectrum. In chromatographic stationary phase design, two fundamental criteria are particularly important: a facile, low-cost synthesis and broad applicability across diverse analyte classes. The present stationary phase fulfils both requirements, as it is prepared from a commercially available starting material via a simple single-step immobilisation onto silica, providing a practical and economical synthetic route alongside wide analytical utility. The molecular architecture of the ligand, incorporating a pH-responsive carboxyl group, a hydrogen-bond-donating and -accepting amide moiety, a polarisation-sensitive sulfur atom, and hydrophobic methyl and methylene units, creates a versatile interaction environment capable of mediating hydrophobic, polar, dispersive, and weak cation-exchange processes. This multifunctional design enables the stationary phase to adapt its selectivity according to analyte structure and mobile-phase conditions, supporting both reversed-phase-like and HILIC-like retention behaviour within a single chromatographic platform. The chromatographic performance of the NAC-derived stationary phase was systematically evaluated using a wide range of chemically and biologically relevant analytes. Under HILIC conditions, the column successfully resolved 7 of the 9 highly polar nucleobases and nucleosides. In reversed-phase mode, compounds with high hydrophobicity-including 6 alkyl benzenes, 4 polycyclic aromatic hydrocarbons, 6 Sudan dyes, 8 anilines, and 7 benzoic acid derivatives-were efficiently separated. Under the same reversed-phase conditions, the stationary phase successfully resolved 10 analytes from a twelve-analyte plant growth regulator mixture and 9 sulphonamides. In addition, a 6 herbicide was also effectively separated, highlighting the multimodal selectivity of the stationary phase. Retention trends were interpreted using analyte logD and pKa values, clarifying the combined contributions of hydrophobic, polar, and weak ion-exchange interactions to overall selectivity. The N-acetyl-l-cysteine-based stationary phase provides a finely balanced interaction profile, enabling high separation performance for analytes spanning from extreme polarity to pronounced hydrophobicity and demonstrating broad analytical utility.},
}

@article {pmid41553565,
year = {2026},
author = {Altındağ, F and İgit, T},
title = {Berberine and N-Acetylcysteine ameliorate diabetes-induced hippocampal damage by inhibiting apoptosis and neuroinflammation, and improve synaptic plasticity in rats.},
journal = {Journal of molecular histology},
volume = {57},
number = {1},
pages = {54},
pmid = {41553565},
issn = {1567-2387},
support = {TDK-2021-9565//Van Yuzuncu Yil University Scientific Research Coordination Unit/ ; TDK-2021-9565//Van Yuzuncu Yil University Scientific Research Coordination Unit/ ; },
mesh = {Animals ; *Apoptosis/drug effects ; *Berberine/pharmacology/therapeutic use ; *Acetylcysteine/pharmacology/therapeutic use ; *Diabetes Mellitus, Experimental/complications/pathology/drug therapy ; Rats ; *Hippocampus/drug effects/pathology/metabolism ; Male ; *Neuronal Plasticity/drug effects ; *Neuroinflammatory Diseases/drug therapy/pathology/etiology ; },
abstract = {Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from impaired insulin secretion and resistance. Berberine (BBR) and N-acetylcysteine are anti-inflammatory and antiapoptotic compounds that have beneficial effects on diabetic complications. This study aimed to investigate the effects of BBR and NAC on the Hippocampus in an experimental diabetes model in rats. Rats were divided into 5 groups: control, diabetes (D), D + NAC, D + BBR, and D + BBR + NAC. STZ (45 mg/kg, i.p.) was administered to the other four groups except the control group. BBR and NAC (50 mg/kg/day) were given intragastrically (i.g.) to the treatment groups for 28 days. Decreased cell body size, pyknotic cells and necrotic neurons were observed in the D group. However, these pathological changes were largely improved in the D + BBR, D + NAC, and D + BBR + NAC. Stereologically, there was no significant difference between the groups in terms of hippocampus volume. The number of pyramidal neurons in CA1 was significantly decreased in the D group. But the number of CA1 pyramidal neurons was higher in both the alone and combined BBR and NAC treatment groups than in the D group. Expressions of Caspase-3, TNF-α, and IL-1β increased in the D group, while expressions of Bcl-2 and SYP decreased. But, BBR and NAC treatments decreased Caspase-3, TNF-α, and IL-1β expressions and increased Bcl-2 and SYP expressions. These results revealed that BBR and NAC can have an antidiabetic effect against the neuronal damage caused by diabetes in the hippocampus CA1 region, suppressing inflammation and apoptosis and preventing the decrease in the number of pyramidal neurons. Also, they reveal that they may modulate synaptic plasticity by increasing synaptophysin expression.},
}

Animals
*Apoptosis/drug effects
*Berberine/pharmacology/therapeutic use
*Acetylcysteine/pharmacology/therapeutic use
*Diabetes Mellitus, Experimental/complications/pathology/drug therapy
Rats
*Hippocampus/drug effects/pathology/metabolism
Male
*Neuronal Plasticity/drug effects
*Neuroinflammatory Diseases/drug therapy/pathology/etiology

@article {pmid41552353,
year = {2025},
author = {Wu, Y and Yao, J and Zhang, Y},
title = {Effects of acetylcysteine combined with bronchoalveolar lavage under fiberoptic bronchoscopy on blood oxygenation and inflammation in elderly severe pneumonia patients.},
journal = {American journal of translational research},
volume = {17},
number = {12},
pages = {9317-9326},
pmid = {41552353},
issn = {1943-8141},
abstract = {OBJECTIVE: To determine the effects of acetylcysteine (NAC) plus bronchoalveolar lavage (BAL) under fiberoptic bronchoscopy (FB) on blood oxygenation and inflammation in elderly severe pneumonia patients.

METHODS: The data of 180 elderly patients with severe pneumonia treated in the Affiliated Hospital 2 of Nantong University between January 2022 and January 2024 were analyzed retrospectively. Eighty-six patients were treated with BAL under FB (BAL group) and 94 patients were treated with NAC based on BAL under FB (BAL + NAC group). Outcomes included pre-/post-treatment blood gas, pulmonary function, inflammatory factors, correlation between inflammatory markers and blood gas parameters, clinical efficacy, symptom resolution time, and adverse reactions.

RESULTS: After treatment, both groups exhibited an increase in arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and decreased C-reactive protein (CRP) and interleukin-6 (IL-6), with more significant changes in the BAL + NAC group (all P < 0.05). Inflammatory markers (CRP/IL-6) were negatively correlated with oxygenation parameters (PaO2/SpO2, all P < 0.01). Additionally, the BAL + NAC group had earlier resolution time of chest pain, expectoration, cough, and lung rales, a higher overall response rate, and no significant difference in adverse reaction incidence versus the BAL group.

CONCLUSION: NAC combined with BAL under FB is effective for elderly patients with severe pneumonia. It can strongly improve the blood gas indexes and lung function, relieve inflammatory reactions, and quickly relieve clinical symptoms, without increasing adverse reactions. Thus it is worthy of clinical promotion.},
}

@article {pmid41550647,
year = {2025},
author = {Zheng, Z and Chen, Z and Zhang, C and Peng, S and Hu, J and Wang, C and Liu, L and Yang, MX and Chen, H},
title = {Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer.},
journal = {Pharmaceutical science advances},
volume = {3},
number = {},
pages = {100088},
pmid = {41550647},
issn = {2773-2169},
abstract = {Multidrug resistance (MDR) poses a critical barrier to chemotherapy efficacy. While the promising agents, aldose reductase inhibitors (ARIs), to overcome multidrug resistance (MDR) has been investigated over recent decades, their underlying mechanisms remain unclear and clinically viable candidates are still lacking. In our study, we identified a novel ARI, 5F-E, which exhibited a more potent sensitizing effect on doxorubicin (DOX) resistant HepG2 cells (HepG2/ADR) compared to epalrestat (EPA). Both 5F-E and EPA were observed to decrease intracellular GSH levels while elevating reactive oxygen species (ROS), Fe[2+] and lipid peroxidation; these effects could be reversed by N-acetyl cysteine (NAC), suggesting that enhanced ferroptosis may be involved in restoring DOX sensitivity. Furthermore, inhibition of AKR1B1 by either compound led to marked reductions in p-STAT3 and SLC7A11 expression, an outcome that was recapitulated by AKR1B1 gene knockdown. The results demonstrate that ARIs exert antitumor effects on HepG2/ADR cells by triggering ferroptosis, a process dependent on AKR1B1/STAT3/SLC7A11 signaling. And, 5F-E, but not EPA, was found to increase intracellular DOX accumulation by inhibiting ABCB1. Our integrated experimental approach reveals that 5F-E exhibits strong chemosensitizing effects against multidrug-resistant liver cancer, highlighting its therapeutic promise.},
}

@article {pmid41547222,
year = {2026},
author = {Su, H and Wu, F and Haque, K and Sha, SH},
title = {Furosemide prevents noise-induced hearing loss and enhances the preventive effect of N-acetylcysteine.},
journal = {Hearing research},
volume = {471},
number = {},
pages = {109537},
doi = {10.1016/j.heares.2026.109537},
pmid = {41547222},
issn = {1878-5891},
abstract = {Disruption of reactive oxygen species (ROS) homeostasis is a key mechanism underlying noise-induced sensory hair cell damage. Antioxidant treatments such as N-acetylcysteine (NAC) have been shown to attenuate noise-induced hearing loss (NIHL), supporting the role of ROS accumulation. However, no FDA-approved pharmaceutical therapy currently exists for the prevention or treatment of NIHL, likely due to the complexity of the damaging mechanisms and the presence of the blood-labyrinth barrier (BLB), which limits drug permeability and prevents therapeutic compounds from reaching effective concentrations via systemic administration. Furosemide (FRS) has demonstrated potential to reduce NIHL and facilitate drug delivery into inner ear by transiently opening the BLB. In this study, we investigated the mechanisms by which FRS pretreatment prevents NIHL. A single dose of 200 mg/kg FRS administered immediately before noise exposure significantly reduced NIHL in FVB/NJ mice. One hour after FRS treatment, the endocochlear potential (EP) was temporarily reduced without altering cochlear sensitivity (ABR thresholds), outer hair cell function (DPOAE amplitudes), or synaptic transmission integrity between hair cells and auditory nerve fibers (suprathreshold ABR wave I amplitudes). Furthermore, this dose of FRS selectively increased stria vascularis permeability to small molecules but not to large protein-bound tracers. Combined treatment with FRS and NAC enhanced NAC's antioxidant effect and additively prevented noise-induced outer hair cell (OHC) loss and NIHL, with OHC loss almost entirely prevented. These findings provide important insight into future strategies for the prevention and treatment of NIHL.},
}

@article {pmid41546819,
year = {2026},
author = {Elhence, A and Mishra, P and Rai, P},
title = {N‑acetylcysteine for post-ERCP pancreatitis prophylaxis: A systematic review and meta-analysis.},
journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology},
volume = {},
number = {},
pages = {},
pmid = {41546819},
issn = {0975-0711},
abstract = {BACKGROUND: Oxidative stress is an early step in the cascade of events triggering post-ERCP pancreatitis (PEP). N-acetylcysteine (NAC), a free radical scavenger, can be used to check this oxidative stress for PEP prophylaxis. METHODS: A systematic search of MEDLINE, EMBASE and Scopus was undertaken from inception to May 30, 2025. The relative risks (RR) of PEP and severe PEP were pooled using a random effects model with the inverse variance method. Funnel plot and Egger's test were used to evaluate publication bias. The quality of studies was assessed using the Cochrane risk of bias tool. Further sensitivity analysis was undertaken to evaluate oral route dosing and a leave-alone-one sensitivity analysis was done to confirm the robustness of the results (PROSPERO ID CRD420251062268).

RESULTS: The five studies meeting the inclusion criteria included 784 participants of which 388 received NAC and 396 received placebo. PEP occurred in 50 participants in the NAC group as compared to 68 participants in the placebo group with a pooled RR of 0.74 (95% confidence interval [CI] 0.48 to 1.15) with moderate heterogeneity, I[2] 35%. Severe PEP occurred in none of the participants administered NAC as compared to three participants administered placebo with a pooled RR of 0.27 (95% CI of 0.03 to 2.43), with I[2] of 0% and no publication bias confirmed by no funnel plot visual asymmetry or Egger's test (p = 0.220). Sensitivity analysis confirmed the robustness of the results.

CONCLUSION: The pooled results of the meta-analysis suggest that NAC prophylaxis does not prevent the occurrence of PEP or severe PEP as compared to placebo.},
}

@article {pmid41541699,
year = {2026},
author = {Ahmad, F and Rendina, BP and Chen, C and Ren, H and Brantner, C and Dukic, T and Miles, D and Winkles, JA and Woodworth, GF and Bhetawal, S and Stone, E and Bar, EE},
title = {Systemic cyst(e)inase administration induces ferroptosis and synergizes with temozolomide in glioblastoma.},
journal = {iScience},
volume = {29},
number = {1},
pages = {114350},
pmid = {41541699},
issn = {2589-0042},
abstract = {Glioblastoma exhibits profound therapeutic resistance, driven by tumor heterogeneity and highly plastic glioma stem cells (GSCs). This study exploits GSC metabolic dependence on cysteine using systemic cyst(e)inase, a cysteine-degrading enzyme. In patient-derived GSCs and orthotopic xenograft models, cyst(e)inase potently inhibited GSC proliferation and extended animal survival by inducing ferroptosis. Mechanistically, cyst(e)inase triggered elevated reactive oxygen species (ROS), glutathione (GSH) depletion, and significant lipid peroxidation. Crucially, these effects were reversed by N-acetylcysteine (NAC), and lipid peroxidation was abrogated by the iron chelator deferoxamine (DFX), unequivocally confirming iron-dependent ferroptosis. Characteristic mitochondrial morphological changes further validated ferroptosis induction. Acyl-CoA synthetase long-chain family member-4 (ACSL4) was identified as essential for this process. Critically, cyst(e)inase synergized with temozolomide (TMZ), markedly enhancing its anti-tumor efficacy and prolonging survival, even in TMZ-resistant xenografts. These findings establish cysteine metabolism as a promising therapeutic target and position cyst(e)inase, especially with TMZ, as a potent strategy to overcome GBM resistance.},
}

@article {pmid41537173,
year = {2026},
author = {Wang, S and Zhang, F and Zhou, X and Yang, J and Li, Z and Li, S and Lu, Q and Sun, H and Liu, P},
title = {Chondrocyte-Targeted Nanoparticles Loaded with N-Acetylcysteine Protect Articular Cartilage and Attenuate Osteoarthritis by Inhibiting Ferroptosis via Glutathione Maintenance.},
journal = {Small science},
volume = {6},
number = {1},
pages = {e202500440},
doi = {10.1002/smsc.202500440},
pmid = {41537173},
issn = {2688-4046},
abstract = {Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation. Abnormal mechanical loading exacerbates intracellular ROS accumulation and glutathione (GSH) depletion. While N-acetylcysteine (NAC) has potent antioxidant properties, its therapeutic potential in OA is limited by rapid degradation and poor intraarticular retention. In this study, chondrocyte-targeted, chondroitin sulfate (CS)-modified PLGA nanoparticles (CS-NAC-NPs) is developed for sustained and localized delivery of NAC. These nanoparticles exhibit excellent physical and chemical properties, biocompatibility, and chondrocyte targeting capabilities. In vitro, CS-NAC-NPs attenuated mechanical stress-induced ROS accumulation, preserved mitochondrial integrity, restored GSH levels, and suppressed ferroptosis, as evidenced by increased GPX4 expression and improved chondrocyte viability. In a murine model of OA, intraarticular injection of CS-NAC-NPs significantly reduced cartilage degradation and osteophyte formation, improved histological scores, and maintained extracellular matrix homeostasis more effectively than free NAC or nontargeted NAC-NPs. Notably, the therapeutic effect is abolished in GPX4-deficient mice, confirming that CS-NAC-NPs act via GPX4-mediated ferroptosis inhibition. Furthermore, in vivo tracking demonstrated excellent joint retention and no off-target toxicity, underscoring their translational safety. This study introduces a novel nanotherapeutic platform that couples biomechanical targeting with redox-responsive delivery to modulate ferroptosis, offering a promising disease-modifying approach for OA treatment.},
}

@article {pmid41535111,
year = {2026},
author = {Afşar, E and Öz, M and Özkan, E and Eranıl, I},
title = {Maternal Immune Activation Disrupts Autophagy and Glucose Homeostasis: Experimental Evidence for the Protective Effects of N-Acetylcysteine on Maternal and Offspring Outcomes in a Rat Model.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70063},
pmid = {41535111},
issn = {1099-1263},
support = {KÜN.2025-BAGP-005//Kapadokya University/ ; },
abstract = {Maternal immune activation during pregnancy has been shown to disrupt maternal glucose regulation, predisposing the mother to postpartum diabetic conditions while also exerting long-lasting metabolic effects on the offspring. This study aimed to investigate the impact of lipopolysaccharide (LPS)-induced maternal immune activation on glucose homeostasis at different postpartum stages, the modulatory role of N-acetylcysteine (NAC), and the effects on the offspring, including sex-specific differences. Albino Wistar female and male rats were used; pregnant females received a single intraperitoneal injection of LPS (0.5 mg/kg) on gestational day 16, with a subset pretreated with NAC (300 mg/kg). Mothers were sacrificed at the end of gestation or on postpartum day 21 (PP21), and offspring were analyzed at PP21. Maternal glucose tolerance was assessed using OGTT, and HOMA-IR and HOMA-β indices were used to determine insulin resistance and β-cell function. Maternal and offspring tissues were analyzed for key markers of signaling, autophagy, proliferation, apoptosis, and inflammation. Phosphorylated protein kinase B (p-Akt), mammalian target of rapamycin (mTOR), Ki-67 (a proliferation marker), phosphorylated AMP-activated protein kinase (p-AMPK), Beclin-1, and microtubule-associated protein 1 light chain 3 beta (LC3B) were measured in tissue homogenates; pancreatic insulin and pro-insulin levels were determined; plasma cytokines, including interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as cleaved caspase-3. All of them were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in plasma using colorimetric assays. At PP0, LPS decreased muscle glucose uptake, increased hepatic gluconeogenesis and glucose output, and enhanced pancreatic insulin production, autophagy, apoptosis, and proliferation while maintaining plasma glucose levels, indicating an adaptive response. NAC improved muscle glucose uptake, suppressed hepatic gluconeogenesis, and normalized pancreatic changes. At PP21, LPS exposure led to increased hepatic gluconeogenesis, impaired pancreatic function, and higher plasma glucose levels. NAC reduced hepatic gluconeogenesis but did not restore glucose balance and worsened pancreatic dysfunction. In offspring of LPS-treated dams, IL-6, TNF-α, and IFN-γ levels decreased, whereas IL-10 increased only in females. Markers of pancreatic apoptosis, autophagy, and proliferation were reduced in both sexes. NAC exposure decreased IL-10 and increased IL-6, TNF-α, and IFN-γ in all offspring and selectively enhanced pancreatic markers in males. Maternal LPS exposure differentially affected glucose regulation through the muscle, liver, and pancreas across postpartum stages. NAC exerted beneficial effects mainly in the early postpartum period but was insufficient later. Furthermore, NAC induced sex-specific effects in the offspring, with a more substantial impact observed in males.},
}

@article {pmid41534829,
year = {2026},
author = {Yadav, A and Richartz, N and Bhagwat, S and Burman, MM and Munthe-Kaas, MC and Skålhegg, BS and Wik, JA and Naderi, S and Blomhoff, HK},
title = {Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111143},
doi = {10.1016/j.jbc.2026.111143},
pmid = {41534829},
issn = {1083-351X},
abstract = {Most children with acute lymphoblastic leukemia (ALL) achieve long-term survival due to intensive multimodal chemotherapy. However, the use of cytotoxic DNA-damaging agents is frequently associated with severe long-term side effects, prompting continued efforts to improve treatment strategies. This study explores the potential of starving the leukemic cells to enhance the efficacy of DNA-damaging therapy in ALL. Previous work demonstrated that cAMP signaling attenuates DNA damage-induced apoptosis in ALL cells, both in vitro and in a xenograft model. The current findings show that glucose and serum deprivation reverse the effect of cAMP, converting it from a survival factor to a promoter of DNA damage-induced apoptosis in ALL-derived cell lines and patient-derived leukemic cells in vitro. The starvation-induced sensitization was independent of p53 but was shown to require increased levels of reactive oxygen species (ROS). In turn, the elevated ROS levels enhanced the activation of the mitogen-activated protein kinase p38 (p38 MAPK). The resulting augmented cell death was inhibited both by the ROS scavenger N-acetyl cysteine (NAC) and the p38 MAPK inhibitor SB 202190. The translational potential of increasing the efficacy of DNA damaging agents in starving ALL cells was supported by in vivo data showing that intermittent fasting, combined with subtherapeutic doses of irradiation, significantly inhibit the leukemia progression in a xenograft model of severe combined immunodeficiency (SCID) mice.},
}

@article {pmid41534554,
year = {2026},
author = {Fu, W and Yan, Y and Shu, C and Xu, C and Chen, Y and Xia, Y and Chen, J and Chen, Y and Cui, R and Zou, P and Ni, D},
title = {6-Methoxydihydrosanguinarine Synergizes with Cisplatin to Enhance Lung Cancer Cell Death via ROS-Mediated Autophagy, ER Stress, and JNK Activation.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178544},
doi = {10.1016/j.ejphar.2026.178544},
pmid = {41534554},
issn = {1879-0712},
abstract = {6-Methoxydihydrosanguinarine is a natural alkaloid derived from medicinal plants that exhibits significant antitumor activity, making it a promising candidate for cancer therapy. However, the exact molecular mechanisms underlying its effects require further investigation. In this study, we investigated the cytotoxicity and underlying mechanisms of 6-Methoxydihydrosanguinarine in human non-small cell lung cancer (NSCLC) cells. Our findings reveal that reactive oxygen species (ROS) accumulation is the key driver of its antitumor activity. Mechanistically, 6-Methoxydihydrosanguinarine activates the JNK signaling pathway and induces endoplasmic reticulum (ER) stress, both of which can be reversed by the ROS scavenger N-acetylcysteine (NAC). Interestingly, 6-Methoxydihydrosanguinarine also activates autophagy, and inhibition of autophagy reverses the JNK and ER stress pathway activation induced by 6-Methoxydihydrosanguinarine. Notably, 6-Methoxydihydrosanguinarine synergistically enhances cisplatin-induced NSCLC cell death, and this synergistic effect is abolished by NAC, highlighting the critical role of ROS accumulation in their combined efficacy. This study systematically elucidates the molecular mechanisms of 6-Methoxydihydrosanguinarine against NSCLC, revealing that, in addition to the JNK and autophagy pathways, ER stress also mediates its antitumor effects. Moreover, our data establish a rationale for exploring 6-Methoxydihydrosanguinarine in NSCLC therapy and highlight its combination with cisplatin as a potentially effective strategy.},
}

@article {pmid41534303,
year = {2026},
author = {Feng, J and Carreño, M and Jung, H and Dayalan Naidu, S and Arroyo-Diaz, N and Ang, AD and Kulkarni, B and Kisielewski, D and Suzuki, T and Yamamoto, M and Hayes, JD and Honda, T and Wilson, L and Leon-Ruiz, B and Eggler, AL and Vitturi, DA and Dinkova-Kostova, AT},
title = {The electrophilic metabolite of kynurenine, kynurenine-CKA, requires C151 in Keap1 to derepress Nrf2.},
journal = {Redox biology},
volume = {90},
number = {},
pages = {104009},
doi = {10.1016/j.redox.2026.104009},
pmid = {41534303},
issn = {2213-2317},
abstract = {The Kelch-like ECH-associated protein 1/Nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) system responds to a wide array of structurally diverse small molecules, of both exogenous and endogenous origin, by inducing a robust cytoprotective program that allows adaptation during oxidative, metabolic and inflammatory stress. Here, we report that exposure to the tryptophan metabolite kynurenine and its electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA) leads to an increase in the abundance of transcription factor Nrf2 and induction of Nrf2-target genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), in murine and human cells. Additionally, both kynurenine and Kyn-CKA activate the aryl hydrocarbon receptor (AhR). Using cellular thermal shift assays, we found that Kyn-CKA increases the thermal stability of Keap1-mCherry fusion protein, but not free mCherry, indicating target engagement of Keap1, the principal repressor of Nrf2. Critically, the ability of Kyn-CKA to increase the abundance of Nrf2 and expression of NQO1 in mouse embryonic fibroblasts (MEFs) expressing wild-type Keap1 was greatly diminished in C151S-Keap1 mutant MEFs. Furthermore, Kyn-CKA reacts with Keap1 C151 much faster in vitro than with the small molecule thiol N-acetyl cysteine, suggesting that Kyn-CKA is targeted to C151 by the surrounding active site. Experiments in wild-type, AhR-knockout, and Nrf2-knockout primary murine bone marrow-derived macrophages showed that Nrf2 is required for the acute anti-inflammatory activity of Kyn-CKA, whereas AhR is dispensable. Together, these findings demonstrate that Kyn-CKA requires C151 in Keap1 to derepress Nrf2 and reveal that Nrf2, but not AhR, is a main contributor to the anti-inflammatory activity of Kyn-CKA in macrophages.},
}

@article {pmid41533906,
year = {2026},
author = {Guo, Y and Luo, S and Li, W and Wang, X and Sun, W and Zha, W and Zhang, R and Liu, D and Wei, M and Zhang, H and Liu, Q and Liu, Z},
title = {Ferroptosis in Meibomian Gland Progenitor Cells Contributes to Pathogenesis of Meibomian Gland Dysfunction.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {1},
pages = {9},
doi = {10.1167/iovs.67.1.9},
pmid = {41533906},
issn = {1552-5783},
mesh = {*Ferroptosis/physiology ; Animals ; Mice ; *Meibomian Glands/pathology/metabolism ; Disease Models, Animal ; *Meibomian Gland Dysfunction/metabolism/pathology/etiology ; *Stem Cells/pathology/metabolism ; Mice, Inbred C57BL ; Humans ; Hydrogen Peroxide ; Male ; Epithelial Cells/metabolism/pathology ; Cells, Cultured ; },
abstract = {PURPOSE: Meibomian gland (MG) atrophy in Meibomian gland dysfunction (MGD) is critically linked to progenitor cell (PC) abnormalities. However, the mechanisms underlying PC abnormalities during MGD pathogenesis remain unclear. This study investigates the role of ferroptosis in MG PC abnormalities during MGD pathogenesis.

METHODS: Three mouse MGD models were established: alkali burn-induced MGD (AK-MGD), blue light-induced MGD (BL-MGD), and age-related MGD (AR-MGD). All exhibited MG atrophy and Lrig1-positive PC abnormalities. Dihydroethidium (DHE) and immunofluorescent staining for Gpx4 and Ptgs2 in MGs were applied to observe the distribution of ferroptotic cells during MGD. Ferroptosis was evaluated in H2O2-treated human MG epithelial cells (HMGECs) by measuring intracellular Fe2+, iron metabolism gene expression, and levels of Gpx4, Slc7a11, and Ptgs2. Ferroptosis signatures were evaluated across models. Ferroptosis inhibitors including Ferrostatin-1 (Fer-1), deferoxamine (DFO), and N-acetylcysteine (NAC) targeting different ferroptosis pathways were applied therapeutically in these MGD models.

RESULTS: All MGD models demonstrated lipid peroxidation and ferroptosis in MG PCs. In HMGECs, we confirmed that H2O2 treatment induced ferroptosis, which was rescued by ferroptosis inhibitors. Acute and chronic MGD models exhibited distinct ferroptosis signatures. Therapeutic intervention with ferroptosis inhibitors ameliorated MGD manifestations to varying degrees in MGD models.

CONCLUSIONS: Ferroptosis in MG PCs contributes to the pathogenesis of MGD. MG PCs are preferentially susceptible to ferroptosis. Pharmacological inhibition of ferroptosis represents a promising therapeutic strategy for MGD.},
}

*Ferroptosis/physiology
Animals
Mice
*Meibomian Glands/pathology/metabolism
Disease Models, Animal
*Meibomian Gland Dysfunction/metabolism/pathology/etiology
*Stem Cells/pathology/metabolism
Mice, Inbred C57BL
Humans
Hydrogen Peroxide
Male
Epithelial Cells/metabolism/pathology
Cells, Cultured

@article {pmid41531336,
year = {2026},
author = {Azuma, R and Yamasaki, T and Sano, K and Mukai, T},
title = {Development of a radioiodinated boronic acid probe for the detection of hydrogen peroxide and peroxynitrite.},
journal = {Free radical research},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/10715762.2026.2617613},
pmid = {41531336},
issn = {1029-2470},
abstract = {Hydrogen peroxide and peroxynitrite play important roles as signaling molecules to maintain the biological functions; however, excess levels of these oxidants are associated with various diseases. Despite their important roles in vivo, effective methods to measure these oxidants in the body with high sensitivity have not yet been established. Therefore, in this study, we aimed to design a radioiodinated boronic acid probe for the in vivo detection of hydrogen peroxide and peroxynitrite. The probe contained boronic acid, a well-known substructure that reacts with hydrogen peroxide and peroxynitrite, at positions 3 and 6 of the xanthene moiety and radioiodine at the phthalide moiety of fluorescein. I-125 labeling was successful, resulting in a radiochemical yield of 60% and radiochemical purity of >95%. In vitro selectivity studies demonstrated that the probe showed significant responses to both hydrogen peroxide and peroxynitrite while exhibiting minimal reactivity toward other reactive oxygen species including superoxide, nitric oxide, and peroxy radicals. In biodistribution studies using lipopolysaccharide (LPS)-treated mice generating reactive oxidants, the boronic acid probe was significantly accumulated in various organs damaged by LPS. However, this phenomenon was inhibited by administration of the antioxidant, N-acetylcysteine, to LPS-treated mice. These results highlight the potential of the developed radioiodinated boronic acid probe to detect hydrogen peroxide and peroxynitrite in living organisms, suggesting it as a candidate for the in vivo detection and functional evaluation of these oxidants in various diseases.},
}

@article {pmid41524784,
year = {2026},
author = {Penney, C and Piper, AK and Holliday, J and Tincknell, G and Joosse, SA and Pantel, K and Brungs, D and Ranson, M},
title = {Adaphostin-induced oxidative stress in oesophageal neuroendocrine carcinoma: a potential therapeutic strategy.},
journal = {Medical oncology (Northwood, London, England)},
volume = {43},
number = {2},
pages = {109},
pmid = {41524784},
issn = {1559-131X},
support = {RSP-316-FY2023//Tour de Cure/ ; RSP-316-FY2023//Tour de Cure/ ; RSP-316-FY2023//Tour de Cure/ ; },
mesh = {Humans ; *Esophageal Neoplasms/drug therapy/pathology/metabolism ; *Carcinoma, Neuroendocrine/drug therapy/pathology/metabolism ; *Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Apoptosis/drug effects ; *Antineoplastic Agents/pharmacology ; Cell Survival/drug effects ; DNA Damage/drug effects ; },
abstract = {Advanced oesophageal neuroendocrine carcinoma (ENEC) is a highly aggressive and rare malignancy with poor prognosis. Due to the rarity of this cancer there are currently no standardised treatment regimens for ENEC, and models to study this disease are difficult to obtain. To address this, we screened our established circulating tumour cell line from a patient with metastatic ENEC, termed UWG01CTC, using the LOPAC[®][1280] drug repurposing library. The redox modulatory agent adaphostin was identified as a potent cytotoxin against UWG01CTC but not non-ENEC cell lines. Secondary adaphostin cell viability screens returned IC50 values of 0.201 ± 0.024 µM confirming the high sensitivity of this ENEC CTC line to the drug. Inclusion of the antioxidant N-acetyl cysteine significantly protected the UWG01CTCs against the cytotoxic effects of adaphostin (IC50 = 0.928 ± 0.425 µM), corroborating a mechanism mediated through the generation of reactive oxygen species (ROS). The expression of DNA damage marker phospho-γH2AX and apoptotic marker cleaved PARP1 were both elevated in cells treated with adaphostin, suggesting that the increased intracellular ROS levels induced by the drug causes downstream DNA damage and ultimately apoptosis. Thus, adaphostin shows promise as a potential new and selective treatment for ENEC.},
}

Humans
*Esophageal Neoplasms/drug therapy/pathology/metabolism
*Carcinoma, Neuroendocrine/drug therapy/pathology/metabolism
*Oxidative Stress/drug effects
Reactive Oxygen Species/metabolism
Cell Line, Tumor
Apoptosis/drug effects
*Antineoplastic Agents/pharmacology
Cell Survival/drug effects
DNA Damage/drug effects

@article {pmid41523401,
year = {2025},
author = {Rasheed, A and Hassan, SH and Mehmood Qadri, H and Ahmed, AB and Ahmed, M and Khan, H and Fatima, N and Azam, A and Dar, SA and Khawaja, AA},
title = {Neurological Manifestations of Aluminum Phosphide (Wheat-Pill/Rice-Pill) Poisoning: A Narrative Review.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e98910},
pmid = {41523401},
issn = {2168-8184},
abstract = {The clinical manifestations of Aluminium Phosphide (AlP) that stem from its misdirected human consumption range from nausea and vomiting to acute respiratory failure, cardiotoxicity and hepatotoxicity, causing sudden death. Currently, there is no standard regimen to deal with this menacing product. This review aimed to highlight the neurological manifestations and treatment options for dealing with wheat pill poisoning. After the literature search, a total of eight studies were included in this study. Study types included five case reports, a prospective case series, a retrospective review, and an autopsy with sample sizes ranging from a single patient to 471 patients. The major symptoms included were dizziness, headache, and weakness in both upper and lower extremities. Reported neurological findings included progressive decline in consciousness, anisocoria with non-reactive pupils, loss of consciousness, convulsions, variable coma grades, and motor deficits. The CT brain findings mentioned in one case report were significant for diffuse bilateral hypoattenuation in the cerebellar hemispheres, midbrain, thalamus, and globus pallidus nuclei. MRI brain revealed multiple cortical and subcortical diffusion restrictions in cerebral hemispheres, consistent with prior global hypoperfusion injury in one case report, while the other showed an acute ischemic infarct in the left posterior cerebral artery (PCA) territory involving left medial temporal, parieto-occipital lobes, left half of the splenium of the corpus callosum and left thalamus. There is some evidence that paraffin oil, co-enzyme Q10, hyperinsulinemia euglycemia, and N-acetylcysteine (NAC) decrease mortality in this poisoning. However, further large-scale randomised controlled trials are needed to definitively evaluate their mortality benefit.},
}

@article {pmid41523131,
year = {2025},
author = {Kim, J and Yi, S and Kang, S and Yae, C and Choi, JM and Kim, SB and Kim, HK},
title = {Liquiritigenin, a licorice-derived flavanone, reduces dry eye pathology via dual anti-inflammatory and antioxidant action.},
journal = {Taiwan journal of ophthalmology},
volume = {15},
number = {4},
pages = {598-610},
pmid = {41523131},
issn = {2211-5072},
abstract = {PURPOSE: Liquiritigenin (LIQ), an active flavanone derived from Glycyrrhiza uralensis, is known to possess potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidative and anti-inflammatory effects of LIQ on experimental dry eye disease (DED) models.

MATERIALS AND METHODS: In vitro effects of LIQ were assessed using a hyperosmotic stress model with assays including quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and immunofluorescent staining. The antioxidative effect was compared with n-acetyl cysteine (NAC) and the anti-inflammatory effect with dexamethasone (DEX). In vivo, DED was induced by desiccation stress in a controlled environmental chamber mouse model. Tear production rate, corneal staining scores, pro-inflammatory cytokine expression, conjunctival goblet cell density, infiltration of T-helper (Th) 17 cells, and reactive oxygen species (ROS) levels in the lacrimal gland were evaluated.

RESULTS: In vitro studies demonstrated that LIQ significantly reduced ROS levels, comparable to NAC, and exhibited anti-inflammatory effects similar to DEX. In the mouse model, LIQ treatment significantly increased tear production and reduced corneal staining scores compared to controls, decreased the expression of Interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-13, tumor necrosis factor α, Interferon γ, restored conjunctival goblet cell density, reduced Th17 cell infiltration, and lowered ROS levels in the lacrimal gland Microarray analysis revealed LIQ regulated cytokine expression and ROS levels through the modulation of the aldo-keto reductase (AKR) superfamily in hyperosmotic stress conditions.

CONCLUSION: LIQ shows potential as a therapeutic agent for DED through its dual anti-inflammatory and antioxidative actions, primarily through modulation of the AKR superfamily.},
}

@article {pmid41519441,
year = {2026},
author = {Li, Z and Xue, Y and Li, K and Qian, M and Wang, F and Luo, JL and Gao, XJ},
title = {Dietary Zinc Deficiency Regulates the ROS/TLR4/NF-κB Pathway to Induce Pancreatic Inflammation and Cell Death in Mice.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110262},
doi = {10.1016/j.jnutbio.2026.110262},
pmid = {41519441},
issn = {1873-4847},
abstract = {Zinc (Zn) deficiency disrupts redox homeostasis in the body. The pancreas is a vital digestive and endocrine organ of the body, and its normal functional operation cannot proceed without the involvement of Zn. In this study, we established in vivo mouse models, including the normal Zn group (CG, 34 mg Zn/kg), Zn-deficient group (LZn, 2 mg Zn/kg), and Zn-supplemented group (HZn, 100 mg Zn/kg), as well as an in vitro Zn-deficient model of Mouse INsulinoma 6 (MIN6) cells. We systematically investigated the effects of Zn deficiency on pancreatic oxidative stress, inflammation, and cell death. The results showed that Zn deficiency significantly decreased the activities of α-amylase and lipase in the pancreas, and led to pancreatic histological damage. Through flow cytometry and detection of antioxidant enzyme activities, it was found that Zn deficiency induces excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the pancreas, and inhibits antioxidant enzyme activities. Using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, it was observed that Zn deficiency activates the TLR4/NF-κB pathway and significantly increases the expression of the NLRP3 inflammasome and inflammatory factors. Furthermore, Zn deficiency significantly upregulates the expression of apoptosis-related factors (Bax, Caspase-3, Caspase-7, Caspase-9) and necroptosis-related factors (RIPK1, RIPK3, MLKL). Treatment with the antioxidant N-acetylcysteine (NAC) reduces the level of ROS and inhibits the activation of the TLR4/NF-κB pathway, thereby alleviating Zn deficiency-induced inflammation and cell death. Taken together, Zn deficiency induces pancreatic inflammation and cell death by regulating the ROS/TLR4/NF-κB pathway.},
}

@article {pmid41519036,
year = {2026},
author = {Yang, X and Zhou, J and Shangguan, D},
title = {Self-oxidation and proximity crosslinking of G-quadruplex in G-quadruplex /hemin peroxidase system.},
journal = {Talanta},
volume = {302},
number = {},
pages = {129344},
doi = {10.1016/j.talanta.2025.129344},
pmid = {41519036},
issn = {1873-3573},
abstract = {G-quadruplex (G4)/hemin peroxidase has emerged as a robust platform for signal amplification in biosensors. While offering distinct advantages over protein enzymes, its susceptibility to inactivation often results in low apparent catalytic activity, thereby limiting broader applications. To address this, we investigated the side reactions occurring during the catalytic process of G4/hemin DNAzyme in both N-acetyl-cysteine (NAC) and H2O2 systems. Notably, high-molecular-weight products were observed when the hemin/G4 ratio exceeded 10. Further analysis revealed that these products primarily resulted from the self-oxidation of G4 sequences or proximity cross-linking with hemin fractions, substrates, and coexisting DNA sequences. Our findings provide critical insights into the inactivation mechanism and offer guidance for enhancing the catalytic efficiency of G4-based biosensors.},
}

@article {pmid41516400,
year = {2026},
author = {Zhang, J and Wang, D and Wang, H and Wu, Q and Liu, M and Li, Q and Gong, Z},
title = {Antioxidant N-Acetylcysteine Facilitates Breast Cancer Metas-Tasis via Immunosuppressive Reprogramming of Neutrophils.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010526},
pmid = {41516400},
issn = {1422-0067},
support = {2023KYQD002//Institute of Health and Medicine, Hefei Comprehensive National Science Center/ ; 32400758//National Natural Science Foundation of China/ ; 32470974//National Natural Science Foundation of China/ ; 82472960//National Natural Science Foundation of China/ ; },
mesh = {*Acetylcysteine/pharmacology ; Animals ; *Neutrophils/immunology/drug effects ; Female ; Mice ; *Breast Neoplasms/pathology/immunology/drug therapy ; *Antioxidants/pharmacology ; Humans ; T-Lymphocytes/immunology/drug effects ; Cell Line, Tumor ; *Lung Neoplasms/secondary/immunology ; },
abstract = {N-acetylcysteine (NAC) is a widely used antioxidant. It has also attracted significant research interest with regard to its role in cancer progression, although the mechanisms involved remain controversial and poorly understood. Here, using murine models of breast cancer metastasis, we found that systemic NAC administration significantly enhanced pulmonary metastasis without altering primary tumor growth in immunocompetent mice, whereas this metastasis-promoting property of NAC was abrogated in T cell-deficient mice. This phenomenon was not due to the direct effects of NAC on T cells or tumor cells, since in vitro studies indicated that NAC exhibited no impact on the effector functions of T cells or the malignant behavior of breast cancer cells. Mechanistically, we demonstrated that NAC endows neutrophils with an immunosuppressive phenotype, which is characterized by the upregulation of immunosuppressive genes, and these NAC-educated neutrophils potently suppress the activation and effector functions of T cells. Collectively, our study reveals a previously unrecognized role played by NAC in regulating breast cancer lung metastasis by orchestrating the myeloid-dependent suppression of anti-tumor T cell immunity and suggests a need to consider immune-mediated mechanisms when evaluating the systemic impact of antioxidant agents in cancer patients.},
}

*Acetylcysteine/pharmacology
Animals
*Neutrophils/immunology/drug effects
Female
Mice
*Breast Neoplasms/pathology/immunology/drug therapy
*Antioxidants/pharmacology
Humans
T-Lymphocytes/immunology/drug effects
Cell Line, Tumor
*Lung Neoplasms/secondary/immunology

@article {pmid41516202,
year = {2025},
author = {Chrószcz-Porębska, M and Waśkiewicz, S and Gołofit, T and Gadomska-Gajadhur, A},
title = {Synthesis and Characterization of Bioactive Oligoitaconates with Amino Acid Functional Groups for Tissue Engineering.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010324},
pmid = {41516202},
issn = {1422-0067},
support = {504/04496/1020/45.010045//Warsaw University of Technology/ ; },
mesh = {*Tissue Engineering/methods ; Cysteine/chemistry ; *Amino Acids/chemistry ; Spectroscopy, Fourier Transform Infrared ; Acetylcysteine/chemistry ; *Biocompatible Materials/chemistry/chemical synthesis ; },
abstract = {Improving the hydrophilicity and tissue adhesion of polymers remains a significant challenge in tissue engineering and is often addressed by introducing functional groups that enhance polymer-tissue interactions. In this field, L-cysteine (Cys) and N-acetyl-L-cysteine (NAC) are particularly interesting due to their functional carboxyl and amine groups, which are prone to hydrogen bonding. Following this trend, this study (i) investigated the feasibility of grafting Cys or NAC onto the linear oligoitaconates via thio-Michael addition and (ii) examined the influence of amino acid incorporation on the material's physicochemical properties. NMR-based calculations confirmed nearly 100% addition efficiency for Cys and a slightly lower, but still high, efficiency for NAC. FT-IR spectra confirmed thiol-based addition, as signal from the Cys/NAC S-H stretching vibrations was not observed in the adduct's spectra. The obtained adducts showed thermal stability up to 200 °C and glass transition temperatures below -20 °C. They were soluble in common organic solvents, except for Cys adducts with oligo(propylene itaconate) and oligo(hexylene itaconate), which were water-soluble only. Due to the low molecular weight (below 1000 g/mol) of oligoitaconates, their adducts cannot serve as standalone scaffold components. However, they showed potential for use as modifiers for high-molecular-weight polylactide or poly(ɛ-caprolactone)-based scaffolds.},
}

*Tissue Engineering/methods
Cysteine/chemistry
*Amino Acids/chemistry
Spectroscopy, Fourier Transform Infrared
Acetylcysteine/chemistry
*Biocompatible Materials/chemistry/chemical synthesis

@article {pmid41512939,
year = {2026},
author = {Lei, Y and Xu, R and Zhan, J and Liu, J},
title = {Activation of the Nrf2-Keap1 Pathway is Associated with NAC-Mediated Alleviation of Nitrite-Induced Oxidative and Endoplasmic Reticulum Stress and Apoptosis in Marsupenaeus japonicus.},
journal = {Fish & shellfish immunology},
volume = {},
number = {},
pages = {111114},
doi = {10.1016/j.fsi.2026.111114},
pmid = {41512939},
issn = {1095-9947},
abstract = {Nitrite accumulation poses a serious threat to aquatic animals in intensive aquaculture systems. Although the antioxidant role of the Nrf2-Keap1 pathway is well established, its regulatory mechanisms under nitrite stress in crustaceans remain poorly understood. This investigation focused on the protective impact of N-acetylcysteine (NAC) on Marsupenaeus japonicus exposed to nitrite toxicity. Shrimp were injected with NAC or PBS and then exposed to 100 mg/L of nitrite nitrogen for 72 hours. The findings revealed that pretreatment with NAC markedly reduced tissue damage in both the hepatopancreas and gills, in comparison to the PBS control group. Additionally, the NAC-treated M. japonicus exhibited upregulated mRNA levels of Nrf2 and its associated antioxidant genes including NQO1, HO-1, CAT, GPx, GST, and SOD, while Keap1 expression was notably suppressed. Additionally, the NAC group downregulated endoplasmic reticulum stress (ERS)-related genes (PERK, eIF2α, ATF4, GRP78, CHOP, IRE1, XBP1, ATF6) and apoptosis-related genes (Caspase-3, Caspase-9, p53, Bax, Apaf-1), while upregulating Bcl-2. Additionally, the NAC group improved total antioxidant capacity (T-AOC) and SOD activity, reduced malondialdehyde (MDA) content and Caspase-3 activity, and decreased the apoptosis rate in the hepatopancreas. The results indicate that NAC alleviates oxidative stress, ERS, and apoptosis triggered by nitrite in M. japonicus. This protective effect is associated with the activation of the Nrf2-Keap1 signaling pathway, suggesting its potential as a potential therapeutic strategy for nitrite toxicity in crustacean aquaculture.},
}

@article {pmid41510997,
year = {2026},
author = {Du, Z and Wu, J and Zhang, T and Ma, X and Li, Z and Xu, J and You, J and Chen, N and Wu, J},
title = {Lack of receptor for advanced glycation end products attenuates obesity-induced adipose tissue senescence in mice.},
journal = {Adipocyte},
volume = {15},
number = {1},
pages = {2611481},
doi = {10.1080/21623945.2025.2611481},
pmid = {41510997},
issn = {2162-397X},
mesh = {Animals ; *Obesity/metabolism/genetics ; *Receptor for Advanced Glycation End Products/metabolism/genetics/deficiency ; Mice ; *Adipose Tissue/metabolism/pathology ; *Cellular Senescence ; Reactive Oxygen Species/metabolism ; Diet, High-Fat/adverse effects ; Mice, Knockout ; Male ; Sirtuin 1/metabolism ; Mice, Inbred C57BL ; Adipocytes/metabolism ; },
abstract = {The receptor for advanced glycation end products (RAGE) and its ligands are critical drivers of adipose tissue inflammation. While RAGE expression increases in ageing cells and pathological conditions, its specific role in high-fat diet (HFD)-induced adipose tissue senescence remains to be fully elucidated. In this study, we investigated the function of RAGE in the development of adipose tissue senescence associated with obesity. We observed that HFD-fed RAGE-deficient (RAGE[-/-]) mice exhibited significantly reduced body weight and adipocyte hypertrophy compared to wild-type (WT) controls. At the molecular level, RAGE[-/-] mice displayed lower mRNA expression of cell cycle regulators and markers of the senescence-associated secretory phenotype. This anti-senescent phenotype was accompanied by decreased reactive oxygen species (ROS) production and elevated expression of anti-oxidant genes. Mechanistically, the lack of RAGE resulted in the upregulation of silent information regulator type 1 (SIRT1) in adipose tissues. Notably, the inhibition of SIRT1 reversed these anti-senescent effects and attenuated anti-oxidant gene expression in RAGE-deficient mice. Furthermore, while antioxidant treatment with N-acetylcysteine (NAC) reduced p53 in WT mice, it failed to fully suppress p16 and p21, whereas NAC treatment in RAGE[-/-] mice significantly downregulated all senescence markers, suggesting a synergistic protective effect. In conclusion, our results demonstrated that RAGE deficiency improved anti-oxidant properties and prevents adipocyte senescence via the SIRT1 signalling pathway, highlighting a potential therapeutic target for obesity-associated tissue dysfunction.},
}

Animals
*Obesity/metabolism/genetics
*Receptor for Advanced Glycation End Products/metabolism/genetics/deficiency
Mice
*Adipose Tissue/metabolism/pathology
*Cellular Senescence
Reactive Oxygen Species/metabolism
Diet, High-Fat/adverse effects
Mice, Knockout
Male
Sirtuin 1/metabolism
Mice, Inbred C57BL
Adipocytes/metabolism

@article {pmid41509112,
year = {2025},
author = {Esparham, F and Rajabian, F and Ghasemzadeh Rahbardar, M and Razavi, BM and Khajavi Rad, A and Amoueian, S and Hosseinzadeh, H},
title = {Evaluating the effect of rutin on contrast-induced nephropathy in rats.},
journal = {Avicenna journal of phytomedicine},
volume = {15},
number = {6},
pages = {1726-1740},
pmid = {41509112},
issn = {2228-7930},
abstract = {OBJECTIVE: Contrast-induced nephropathy is a common cause of acute kidney injury, and oxidative stress plays an important role in its development. The flavonoid rutin is of interest for its potential antioxidant properties. This study aimed to assess the protective effects of rutin against contrast-induced renal toxicity in rats.

MATERIALS AND METHODS: Eight groups of male Wistar rats (n=6 in each group) were designed: (1) Sham, (2) Premedication-control (N(ω)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.)+indomethacin (10 mg/kg, i.p.)), (3) Contrast medium (L-NAME+indomethacin+diatrizoate (12.5 ml/kg, i.p)), (4-6) Rutin (25, 50, and 100 mg/kg, p.o., for 7 days)+L-NAME+indomethacin+ diatrizoate, (7) N-acetylcysteine (NAC, 125 mg/kg, i.p.), L-NAME+indomethacin+diatrizoate, and (8) Rutin-alone (100 mg/kg). All study groups except for the sham and rutin-alone were subjected to 48 hr of water deprivation. On day 8, blood and kidney samples were isolated to evaluate oxidative stress, biochemical and histopathological changes.

RESULTS: The levels of serum blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA) were raised by diatrizoate, while glutathione (GSH) levels in renal tissue were reduced. Rutin (25, 50, and 100 mg/kg) improved biochemical parameters and oxidative stress. Diatrizoate also resulted in interstitial edema, medullary congestion, proteinaceous casts, and severe tubular necrosis in kidney tissue. Rutin (100 mg/kg) reduced tubular necrosis and interstitial edema but had no significant effect on the formation of medullary congestion and proteinaceous casts in renal tissue.

CONCLUSION: Oxidative stress triggered by contrast-induced nephropathy is caused by a rise in MDA and a decline in GSH amounts. Rutin protects kidney tissue against contrast-induced damage through its antioxidant effect.},
}

@article {pmid41504138,
year = {2026},
author = {Singh, P and Kumari, S and Singh, R},
title = {Intranasal Curcumin and N-Acetyl l-Cysteine (NAC) Attenuates Dibutyl Phthalate (DBP)-Aggravated Airway Inflammation by Targeting Ferroptosis via Nrf-2/GPx4-SLC7A11.},
journal = {Environmental toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1002/tox.70035},
pmid = {41504138},
issn = {1522-7278},
support = {//Department of Biotechnology, Ministry of Science and Technology, India/ ; //Institute of Eminence (IOE), Banaras Hindu University/ ; },
abstract = {Ferroptosis plays a significant role in the pathophysiological development of several diseases. It is an iron-dependent type of controlled cell death triggered by oxidative stress and lipid peroxidation. Nrf2, a key regulator of the antioxidant response, protects cells from ferroptosis by regulating genes involved in iron metabolism and the synthesis and breakdown of glutathione (GSH). This study was undertaken to investigate the relationship between Nrf2-mediated oxidative stress and ferroptosis in allergic asthmatic mice, particularly when the environmental toxin DBP is present. DBP disrupts iron homeostasis and causes asthma exacerbation by inducing iron accumulation and increasing hemosiderin-loaded macrophage numbers in the lungs. N-acetylcysteine (NAC) and curcumin antioxidant treatments significantly reduced ferroptotic damage, increased downstream targets such as GPx4, SLC7A11, and SLC40A1, and activated the Nrf2 pathway. On the other hand, ferroptosis and lung damage were exacerbated by Nrf2 suppression. In addition to elevating reactive oxygen species (ROS), nitric oxide (NO), and 8-oxoguanine (8-oxodG), DBP exposure also decreased GSH, GPx, and SOD, which led to lipid peroxidation and increased levels of malondialdehyde (MDA). These results demonstrate the therapeutic potential of Nrf2 targeting to prevent oxidative lung injury and ferroptosis in asthma triggered by DBP.},
}

@article {pmid41504037,
year = {2025},
author = {Qiao, W and Huang, M and Chen, L and Goltzman, D and Miao, D},
title = {Active Vitamin D Insufficiency Accelerates Skeletal Aging via Oxidative Stress and p16-Mediated Senescence.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {12},
pages = {46123},
doi = {10.31083/FBL46123},
pmid = {41504037},
issn = {2768-6698},
support = {81730066//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Oxidative Stress ; *Vitamin D Deficiency/metabolism ; Male ; Mice ; *Cellular Senescence ; *Aging/metabolism ; *Cyclin-Dependent Kinase Inhibitor p16/metabolism/genetics ; DNA Damage ; Reactive Oxygen Species/metabolism ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; *Bone and Bones/metabolism/pathology ; Acetylcysteine/pharmacology ; Vitamin D ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Vitamin D is essential for skeletal health, but its role in redox homeostasis and cellular senescence during aging in vivo is unclear. We therefore investigated whether active vitamin D insufficiency accelerates bone loss via oxidative stress and senescence pathways.

METHODS: Male wild-type (WT) and Cyp27b1 haploinsufficient mice (modeling vitamin D insufficiency) were treated with N-acetylcysteine (NAC) or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Double-mutant p16[-/-]Cyp27b1[+/-] mice were used to assess the role of the tumor suppressor protein p16. Mice were maintained until 8 months of age in a specific pathogen-free facility. Outcomes included lifespan (n = variable per group, monitored daily); generation of oxidative stress (determined by serum malondialdehyde [MDA] levels via assay kit); generation of bone reactive oxygen species [ROS] (determined via flow cytometry), development of DNA damage (indicated by 8-hydroxy-2'-deoxyguanosine [8-OHdG] and γ-H2A.X generation and determined via immunohistochemistry and Western blot); and senescence (assessed by generation of β-galactosidase [β-gal], p16, and senescence-associated secretory phenotype [SASP] cytokines as determined via staining, blot, and real-time reverse transcription polymerase chain reaction). Additionally, bone microarchitecture was examined via micro-computed tomography and histomorphometry. Data from at least 5 mice per group were analyzed using unpaired Student's t-test for two-group comparisons and two-way analysis of variance for multi-group comparisons, with significance at p < 0.05.

RESULTS: Compared with wild-type controls, Cyp27b1[+/-] mice showed a significantly shorter lifespan, higher oxidative stress, greater DNA damage, increased senescence markers, and lower trabecular bone volume (all p < 0.05). In Cyp27b1[+/-] mice, treatment with either N-acetylcysteine or 1,25(OH)2D3 significantly improved survival, reduced oxidative stress and DNA damage, attenuated senescence markers, and increased bone volume relative to untreated Cyp27b1[+/-] mice (p < 0.05 for all relevant comparisons; n = 5 per group). Genetic deletion of p16 in Cyp27b1[+/-]mice similarly increased bone volume and reduced senescence-associated readouts compared with Cyp27b1[+/-] controls (p < 0.05; n = 5).

CONCLUSIONS: Active vitamin D insufficiency accelerates skeletal aging in vivo through a pathway involving reactive oxygen species-DNA damage-p16/senescence-associated secretory phenotype. Antioxidants, vitamin D repletion, or p16 inhibition rescued bone loss, highlighting redox-senescence axes as potential therapeutic targets for osteoporosis.},
}

Animals
*Oxidative Stress
*Vitamin D Deficiency/metabolism
Male
Mice
*Cellular Senescence
*Aging/metabolism
*Cyclin-Dependent Kinase Inhibitor p16/metabolism/genetics
DNA Damage
Reactive Oxygen Species/metabolism
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics
*Bone and Bones/metabolism/pathology
Acetylcysteine/pharmacology
Vitamin D
Mice, Inbred C57BL

@article {pmid41503729,
year = {2026},
author = {Yu, T and Wang, B},
title = {N-Acetylcysteine Attenuates Benzo[a]pyrene-Exacerbated Asthma Lung Injury by Inhibiting Mucous Hypersecretion and Apoptosis via the ROS/CREB/ERK Pathway.},
journal = {The Journal of asthma : official journal of the Association for the Care of Asthma},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/02770903.2025.2612521},
pmid = {41503729},
issn = {1532-4303},
abstract = {OBJECTIVE: To investigate the protective effect of N-acetylcysteine (NAC) against benzo[a]pyrene (BaP)-aggravated lung injury in asthma and to elucidate whether it is mediated through the ROS/CREB/ERK signaling pathway.

METHODS: Twenty-four BALB/c mice were randomly divided into Control, Model (OVA + BaP), and Intervention (OVA + BaP + NAC) groups. An aggravated asthma model was established by ovalbumin (OVA) sensitization/challenge combined with intratracheal instillation of BaP. The NAC group received NAC via gavage. Airway inflammation and mucus secretion were assessed by H&E and PAS staining. Serum IgE levels were measured by ELISA. SOD activity and MDA content were detected using commercial kits. ROS levels in lung tissue were observed by fluorescence staining. The mRNA expression of mucin genes (MUC5AC, MUC5B, MUC16, etc.) was detected by qPCR. The protein expression of apoptosis-related markers (Bax, Bcl-2) and signaling pathway components (p-ERK1/2, p-CREB) was measured by Western Blot.

RESULTS: Compared with the Model group, NAC intervention significantly alleviated airway inflammatory cell infiltration, mucus hypersecretion, and epithelial damage, and reduced serum IgE levels. Meanwhile, NAC effectively decreased ROS and MDA levels, increased SOD activity in lung tissue, reversed the BaP-induced upregulation of MUC5AC, MUC5B, and MUC16 genes, and modulated the Bax/Bcl-2 ratio to inhibit apoptosis. Mechanistically, NAC significantly inhibited BaP-induced phosphorylation of ERK1/2 and CREB.

CONCLUSION: NAC can mitigate BaP-induced airway mucus hypersecretion and apoptosis, thereby alleviating asthma lung injury, by scavenging ROS and inhibiting the overactivation of the ROS/CREB/ERK signaling pathway. This study provides experimental evidence supporting NAC as a potential therapeutic strategy for preventing and treating air pollution-associated asthma.},
}

@article {pmid41503441,
year = {2026},
author = {Gu, HJ and Han, GU and Kim, SG and Moon, SH and Shin, SH and Ryu, BY},
title = {Bisphenol AF induces mouse spermatogonia apoptosis via reactive oxygen species-mediated Beclin-1 cleavage.},
journal = {Toxicological research},
volume = {42},
number = {1},
pages = {113-125},
doi = {10.1007/s43188-025-00321-z},
pmid = {41503441},
issn = {1976-8257},
abstract = {Oxidative stress plays an essential role in homeostasis, cell signaling, and host defense mechanisms. However, excessive levels are harmful and cause DNA damage, lipid peroxidation, and mitochondrial dysfunction, ultimately causing cell death. Oxiapoptophagy, a cell death mechanism driven by excessive reactive oxygen species (ROS), involves both apoptosis and autophagy. This study investigated the mechanisms underlying bisphenol AF (BPAF)-induced cell death in mouse GC-1 spermatogonia (spg), using 7-ketocholesterol (7KC) as a reference oxiapoptophagy inducer. Both 7KC and BPAF inhibited GC-1 spg proliferation with comparable half-maximal inhibitory concentration (IC50): 16.9 µM for 7KC and 16.5 µM for BPAF. However, BPAF induced significantly higher ROS levels than 7KC. At 20 µM, BPAF predominantly triggered apoptosis, whereas 7KC mainly promoted autophagy. BPAF evidently increased cleaved Beclin-1 levels, suggesting a transition from autophagy to apoptosis and implicating Beclin-1 cleavage as key modulator of apoptosis. Furthermore, the ROS scavenger N-acetyl cysteine (NAC) reduced BPAF-induced ROS production, suppressed Beclin-1 cleavage, and partially restored GC-1 spg proliferation. Collectively, these findings demonstrate that BPAF-induced spermatogonia toxicity is mediated by ROS and regulated through Beclin-1 cleavage, underscoring the need for further investigation of BPAF's reproductive toxicity and the development of strategies to protect male reproductive health.},
}

@article {pmid41502527,
year = {2025},
author = {Shi, H and Chen, L and Huang, J and Lin, X and Huang, L and Tang, M and Lu, K and Wang, W and Zhu, M},
title = {CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma.},
journal = {Oncology research},
volume = {34},
number = {1},
pages = {17},
doi = {10.32604/or.2025.068737},
pmid = {41502527},
issn = {1555-3906},
mesh = {Humans ; *Carcinoma, Hepatocellular/pathology/genetics/metabolism ; *Liver Neoplasms/pathology/genetics/metabolism ; Apoptosis/genetics ; *Reactive Oxygen Species/metabolism ; *Mitochondria/metabolism/pathology ; *p38 Mitogen-Activated Protein Kinases/metabolism ; Cell Proliferation ; *MAP Kinase Signaling System ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Prognosis ; JNK Mitogen-Activated Protein Kinases/metabolism ; Cell Movement ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms, with a particular focus on mitochondrial function and apoptosis.

METHODS: Differential expression analyses were performed across three datasets-The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), GSE36076, and GSE95698-to identify overlapping differentially expressed genes (DEGs). A prognostic risk model was then constructed. Cysteine/serine-rich nuclear protein 1 (CSRNP1) expression levels in HCC cell lines were assessed via western blot (WB) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of CSRNP1 knockdown or overexpression on cell proliferation, migration, and apoptosis were evaluated using cell counting-8 (CCK-8) assays, Transwell assays, and flow cytometry. Mitochondrial ultrastructure was examined by transmission electron microscopy, and intracellular and mitochondrial reactive oxygen species (mROS) levels were measured using specific fluorescent probes. WB was used to assess activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) pathway, and pathway dependence was examined using the ROS scavenger N-Acetylcysteine (NAC) and the JNK inhibitor SP600125.

RESULTS: A six-gene prognostic model was established, comprising downregulated genes (NR4A1 and CSRNP1) and upregulated genes (CENPQ, YAE1, FANCF, and POC5) in HCC. Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis. Conversely, CSRNP1 overexpression impaired mitochondrial integrity, increased both mitochondrial and cytoplasmic ROS levels, and activated the JNK/p38 MAPK pathway. Notably, treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.

CONCLUSION: CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC. It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner. These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.},
}

Humans
*Carcinoma, Hepatocellular/pathology/genetics/metabolism
*Liver Neoplasms/pathology/genetics/metabolism
Apoptosis/genetics
*Reactive Oxygen Species/metabolism
*Mitochondria/metabolism/pathology
*p38 Mitogen-Activated Protein Kinases/metabolism
Cell Proliferation
*MAP Kinase Signaling System
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Prognosis
JNK Mitogen-Activated Protein Kinases/metabolism
Cell Movement

@article {pmid41500430,
year = {2026},
author = {Zhang, W and Lin, H and Xiao, Z and Shen, D and Xia, D and Qiu, Z and Zhang, X and Zhao, Q},
title = {Trichlorfon induces damage of growth and development of Bombyx mori through ferroptosis pathway.},
journal = {Insect biochemistry and molecular biology},
volume = {},
number = {},
pages = {104488},
doi = {10.1016/j.ibmb.2026.104488},
pmid = {41500430},
issn = {1879-0240},
abstract = {Trichlorfon (TCF), an organophosphorus pesticide, has long been used in agriculture as an insecticide for crop protection. However, its residual presence has caused significant economic losses to the sericulture industry, hindering the development of Bombyx mori (B. mori) farming. Although previous studies have investigated the toxicity of TCF to silkworms, the detailed toxic effects and molecular mechanisms remain poorly understood. In this study, the potential molecular targets and mechanisms of TCF-induced injury in silkworms were investigated in vivo and in vitro by combining RNA sequencing, qRT-PCR and other techniques. It is found that TCF exposure leads to damage of growth and development in silkworms, as evidenced by reduced body weight, increased mortality, and decline of cluster, cocooning, pupation and egg production. Further RNA sequencing analysis identified several differentially expressed genes, particularly LOC101744260, as well as altered pathways, notably the glutamine metabolism pathway-both of which are closely associated with ferroptosis. In vivo and in vitro experiments have confirmed that the expression levels of ferroptosis-related genes, including Fer HCH, Fer 2LCH, Keap1, Tf, Gtpx and SOD1 exhibited significant changes in expression levels. These changes are accompanied by elevated intracellular Fe[2+] and Fe[3+] levels and oxidative stress. Moreover, N-acetylcysteine (NAC) treatment partially reverses TCF-induced growth and developmental impairments at the individual and cellular levels. Taken together, these results indicate for the first time that TCF exposure induces damage of growth and development in silkworms by activating the ferroptosis pathway. This study provides a new insight into the toxic mechanisms of TCF in silkworms and offers a theoretical basis for the prevention and control of pesticide pollution in silkworms industry.},
}

@article {pmid41496214,
year = {2025},
author = {Seomoon, K and Lee, H and Hong, T and Park, J and Ying, W and Song, G and Jeong, W and Lim, W},
title = {Multi-organ toxicity via oxidative stress and disrupting mitochondrial plasticity induced by bendiocarb in zebrafish.},
journal = {Redox biology},
volume = {89},
number = {},
pages = {104001},
doi = {10.1016/j.redox.2025.104001},
pmid = {41496214},
issn = {2213-2317},
abstract = {Bendiocarb, a carbamate insecticide, is widely applied in various circumstances; however, it poses a potential threat to various non-target organisms. Although many researchers have focused on defining the toxic effects of bendiocarb, those associated with early and organ development remain poorly understood. In this study, we evaluated the developmental and organ-specific toxic mechanisms of bendiocarb in a zebrafish model. Exposure of bendiocarb decreased viability of zebrafish larvae by changing morphology and inducing production of reactive oxygen species with a decrease of the expression of antioxidant genes cat and sod2. In addition, bendiocarb affected mitochondrial bioenergetics and plasticity with reduction of mitochondrial complexes I, III, and V related genes leading to suppression of ATP generation. To investigate multi-organ toxic effects of bendiocarb, various transgenic zebrafish were utilized, for example, cardiac toxicity, impaired vasculature, and interfered blood flow were confirmed using cmlc2:dsRed, fli1a:EGFP, and gata1a:dsRed. Hepatotoxicity was examined using the fabp10a:dsRed model, and pancreatic toxicity was elucidated using the elastase:EGFP and insulin:EGFP models. Additionally, abnormal neuronal development was observed following treatment with olig2:dsRed and gad1b:EGFP. Moreover, changes at the molecular level by whole mount in situ hybridization and qPCR analyses were consistent with our observations. Furthermore, N-acetylcysteine (NAC) co-treatment substantially ameliorated developmental toxicity across multiple organ systems, including the cardiovascular, metabolic, and nervous systems. Taken together, this study provides novel perspectives on the system-level toxicity of bendiocarb and its molecular mechanisms of action in zebrafish.},
}

@article {pmid41493763,
year = {2026},
author = {He, Q and Hu, X and Li, X and Li, N and Wu, JL},
title = {Covalently Active Metabolites of Bisphenol A Analogs by Mass Spectrometry Diagnostic Ions: Possible Mechanisms of Their Toxicity.},
journal = {Chemical research in toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.chemrestox.5c00417},
pmid = {41493763},
issn = {1520-5010},
abstract = {Bisphenol A analogs (BPs), used as BPA alternatives, have drawn great concerns due to their potential adverse effects. Studies have shown that reactive metabolites (RMs) formed in vitro and in vivo could covalently bind to nucleophilic macromolecules to elicit toxicity. However, the bioactivation potential of BPs and their capacity to covalently modify amino acid residues within proteins have been poorly characterized. Thus, this study systematically characterized the metabolic activation of eight BPs and their reactivity toward cysteine. Using N-acetylcysteine (NAC) as a trapping agent to capture RMs, we developed a novel nontargeted fragment screening strategy for cysteine adduct identification and mechanistic exploration. Integrating calculated electron affinity results, mechanistic analyses revealed a common activation pathway across multiple BPs involving oxidation, ipso-addition, and ipso-substitution. Also, the abundances of cysteine adducts correlated with metabolic rates of individual BPs, underscoring structure-reactivity relationships. These results provided critical mechanistic insight into BPs bioactivation, implicating their potential toxicity risk and supporting environmental risk evaluation.},
}

@article {pmid41492367,
year = {2026},
author = {Zhang, Y and Jin, Z and Xu, L and Zhong, Z and Wang, X and Gao, C and Li, L},
title = {ROS-scavenging nanoparticles loaded with tectorigenin protect against acetaminophen-induced hepatotoxicity by interrupting the calcium/ROS-mediated pathogenic endoplasmic reticulum-Mitochondrial signaling cascade.},
journal = {Bioactive materials},
volume = {58},
number = {},
pages = {408-421},
pmid = {41492367},
issn = {2452-199X},
abstract = {Acetaminophen (APAP) overdose is a leading cause of acute liver injury (ALI) and acute liver failure (ALF) worldwide, representing a major clinical and public health challenge due to its rapid onset and high morbidity. Current clinical treatment is limited to N-acetylcysteine (NAC), but its efficacy is highly time-dependent and the prolonged regimen imposes additional clinical burdens and side effects. Natural compounds hold tremendous promise for hepatoprotection, but their clinical translation is limited by unfavorable physicochemical and pharmacokinetic properties. In this study, tectorigenin (Tec), an isoflavone possessing anti-inflammatory and antioxidative activity, was encapsulated within a reactive oxygen species (ROS)-responsive nanoplatform (PBHB@Tec) to enhance bioavailability and enable site-selective hepatoprotection. PBHB@Tec possessed diameters compatible with passage through hepatic sinusoidal fenestrae into the space of Disse enabling direct hepatocyte interaction, while exhibiting potent ROS scavenging activity and undergoing ROS-triggered morphological degradation that accelerated Tec release under oxidative conditions. In an APAP-induced ALI mouse model, PBHB@Tec markedly attenuated ALI phenotypes. Mechanistically, PBHB@Tec reduced endoplasmic reticulum (ER) stress, which alleviated ER Ca[2+] leak and subsequently prevented mitochondrial Ca[2+] overload. This, in turn, lowered mitochondrial ROS production and restored antioxidant defenses, collectively disrupting the feedforward calcium/ROS apoptotic cascade. These broad improvements in ER-mitochondrial homeostasis positioning PBHB@Tec as a promising ROS-responsive nanotherapy for APAP-induced hepatotoxicity.},
}

@article {pmid41490888,
year = {2026},
author = {Wei, Y and Sun, D and Wu, F and Zhang, S and Cai, B and Ma, Y and Zheng, H and Shi, X and Li, Y and Le, S and Zhou, X and Jin, L and Wang, J},
title = {Mitochondrial retrograde signaling initiates HIF-1α/BNIP3/NIX-mediated mitophagy in Tibetan high-altitude adaptation.},
journal = {Cell death discovery},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41420-025-02933-8},
pmid = {41490888},
issn = {2058-7716},
support = {U23A20475, 32288101, 82300574, 31871436//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Genome-wide studies have identified the nuclear gene EPAS1 and the mitochondrial M9a haplogroup as pivotal contributors to hypoxia adaptation in Tibetans. However, the interaction between these two genetic components is not yet clear. In this study, we demonstrate that cells harboring the Tibetan-specific M9a haplogroup with downregulated EPAS1 (M9a+shEPAS1) exhibit enhanced cellular function under hypoxic conditions. These cells display improved mitochondrial function and proliferation, alongside reduced apoptosis and mtDNA-mediated inflammation, driven by the activation of HIF-1α-BNIP3/NIX-mediated mitophagy and an increase in reactive oxygen species (ROS) levels. Furthermore, treatment with N-acetylcysteine (NAC), PX-478, or Mdivi-1 significantly attenuated BNIP3/NIX-mediated mitophagy, leading to an aggravation of mtDNA-mediated inflammation and apoptosis in M9a+shEPAS1 cells during hypoxia. This study first reveals that ROS-driven HIF-1α-BNIP3/NIX-mediated mitophagy mitigates hypoxia-induced inflammation and apoptosis, contributing to the enhanced hypoxia adaptation observed in Tibetans. HIF-1α-BNIP3/NIX-mediated mitophagy may offer potential therapeutic targets for high-altitude illnesses by regulating cellular energy metabolism and inflammation.},
}

@article {pmid41486713,
year = {2025},
author = {Shruthi, T and Govindan, L and Kanagarajan, SS},
title = {Fluoxetine versus N-acetylcysteine in reducing craving in Indian men with alcohol dependence syndrome: a randomised controlled trial.},
journal = {East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan},
volume = {35},
number = {4},
pages = {224-228},
doi = {10.12809/eaap2591},
pmid = {41486713},
issn = {2224-7041},
mesh = {Humans ; Male ; *Acetylcysteine/therapeutic use/adverse effects ; Adult ; *Craving/drug effects ; *Alcoholism/drug therapy/psychology ; Middle Aged ; *Fluoxetine/therapeutic use/adverse effects ; India ; Young Adult ; Treatment Outcome ; Adolescent ; Recurrence ; Aged ; },
abstract = {OBJECTIVES: To compare the efficacy of fluoxetine and N-acetylcysteine (NAC) in reducing craving, relapse, and improving treatment adherence in men with alcohol dependence syndrome (ADS).

METHODS: Men aged 18 to 65 years with a diagnosis of ADS who had maintained ≥7 days of abstinence from alcohol were recruited. Participants were randomised in a 1:1 ratio to receive either oral fluoxetine 20 mg/day or NAC 600 mg twice/day for 12 weeks. Participants were followed up at weeks 4, 8, and 12. Outcome measures included the Penn Alcohol Craving Scale (PACS), relapse rate, treatment adherence, and adverse effects.

RESULTS: In total, 100 men were equally randomised to receive either fluoxetine or NAC. Both fluoxetine and NAC were effective in lowering PACS scores over 12 weeks, with scores being lower in the NAC group than in the fluoxetine group at week 4 (15.4 vs 17.6, p = 0.03), week 8 (11.3 vs 14.2, p = 0.002), and week 12 (7.8 vs 11.1, p < 0.001). The reduction in PACS scores was significantly greater in the NAC group from week 4 onward. Relapse rates were lower in the NAC group (18.0% vs 32.0%, p = 0.049). Treatment adherence was higher (but not significantly) in the NAC group (90.0% vs 84.0%, p = 0.38). Both medications were well tolerated. All adverse effects were mild.

CONCLUSION: Both fluoxetine and NAC were effective in reducing alcohol craving over 12 weeks, with greater reduction in the NAC group at each follow-up assessment. The NAC group also had a lower relapse rate and better adherence and tolerability.},
}

Humans
Male
*Acetylcysteine/therapeutic use/adverse effects
Adult
*Craving/drug effects
*Alcoholism/drug therapy/psychology
Middle Aged
*Fluoxetine/therapeutic use/adverse effects
India
Young Adult
Treatment Outcome
Adolescent
Recurrence
Aged

@article {pmid41486682,
year = {2026},
author = {Kiel, A and Luty, M and Kralemann-Köhler, A and Helweg, LP and Schürstedt-Seher, J and Kotlinowski, J and Pospíšil, J and Lekka, M and Ly, TD and Huser, T and Schulte Am Esch, J and Hübner, W and Szafranska, K and Zapotoczny, B},
title = {Offsetting ROS-Mediated Arrest of Endothelial Fenestration Dynamics Permits Long-Term Optical Super-Resolution Imaging Validated by AFM.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c22333},
pmid = {41486682},
issn = {1944-8252},
abstract = {Advances in cell biology create the demand for developing methods capable of resolving the structure and dynamics of subcellular organelles in living cells, which are beyond the reach of classical microscopy. Live-cell super-resolution fluorescence imaging provides this capability; however, in practice, its application is limited by phototoxicity, which perturbs cellular features and interferes with natural mechanisms of biological processes, providing a biased interpretation. Liver Sinusoidal Endothelial Cells (LSECs), with their nanoscale fenestrations that are physiologically critical and highly dynamic structures in the native state, represent a particularly demanding system for fluorescence-based microscopy. Here, we identify that photoactivation-generated reactive oxygen species (ROS) are the principal cause of fenestration arrest in fluorescence microscopy. By implementing three-dimensional super-resolution structured illumination microscopy (3D SR-SIM), we systematically evaluate a range of fluorophores and ROS scavengers to optimize imaging conditions. By combining BioTracker staining, carbon dioxide-independent medium supplemented with N-acetylcysteine (NAC), we preserved fenestration dynamics without altering the number/size of fenestrations. Complementary atomic force microscopy (AFM) validated that the combination of light and dye exposure impairs fenestration dynamics through ROS, in the absence of antioxidant supplementation. Additionally, AFM provides insights into the cells' nanomechanical changes upon illumination. Our findings confirm the mechanism underlying imaging-induced artifacts in LSECs observed in the literature and provide a broadly applicable framework for extending live-cell super-resolution microscopy of living cells.},
}

@article {pmid41485463,
year = {2026},
author = {Patwardhan, UM and Soni, C and Mannava, S and Campwala, I and Vacaru, A and Cope, J and Soundappan, SV and Moores, D and Radulescu, A and Cromeens, BP and Waltz, P and Gollin, G},
title = {Operative Management of Meconium Ileus With Needle Injection of N-Acetylcysteine.},
journal = {The Journal of surgical research},
volume = {318},
number = {},
pages = {9-13},
doi = {10.1016/j.jss.2025.12.001},
pmid = {41485463},
issn = {1095-8673},
abstract = {INTRODUCTION: The operative management of meconium ileus in infants often includes enterotomy or appendectomy with N-acetylcysteine (NAC) instillation. Some have adopted an approach whereby NAC is instead injected directly into the meconium-bearing ileum at multiple sites with a small-gauge needle. We hypothesized that this technique would facilitate the mobilization of meconium without an enterotomy or even appendectomy.

METHODS: A retrospective study of neonates who underwent operative management of meconium ileus at 6 hospitals in the United States and Australia between 2010 and 2021 was conducted. Outcomes after NAC instillation at multiple sites with a 27G needle injection versus enterotomy or the appendiceal stump were assessed. The primary outcomes were operative duration and time to full enteral feedings.

RESULTS: Inclusion criteria were met in 52 patients and 9 (17.3%) underwent needle injection of NAC. Meconium was evacuated via the appendiceal stump (33%) or colon and passed via rectum (67%) in all patients in whom NAC was injected via a needle but in only 4 (9%) of those who were administered NAC via an enterotomy. Time to first stool, first enteral feeding, goal enteral feedings, and postoperative length of stay did not differ based on the operative approach. The median operative time in the needle injection group was significantly shorter (90 versus 133 min, P = 0.009).

CONCLUSIONS: Needle injection of NAC appears to be safe and effective in clearing inspissated meconium in neonates who required operative management. It obviated the need for enteral violation in the majority of cases and resulted in reduced operative time.},
}

@article {pmid41483163,
year = {2026},
author = {Nicholson, SE and Hewitt, KA and Brauen, CS and Henricks, AM},
title = {Prenatal antioxidant treatment suppresses maternal immune activation induced increases in alcohol self-administration in a sex-specific manner.},
journal = {Psychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41483163},
issn = {1432-2072},
support = {Alcohol and Drug Abuse Research Program//Alcohol and Drug Abuse Research Program/ ; },
abstract = {RATIONALE: Prenatal exposure to infection is a risk factor for neuropsychiatric disorders that often co-occur with alcohol misuse. However, the mechanisms by which early exposure to infection might increase the risk of such disorders remains unclear. One hypothesis is that prenatal stressors interact with adolescent stressors (i.e., "two-hits") to promote alcohol misuse development.

OBJECTIVES: The current project tested whether maternal immune activation (MIA) combined with adolescent alcohol exposure (AA) increases the motivation to work for alcohol and negative affect in adulthood, and whether prenatal antioxidant treatment prevents these effects.

METHODS: Pregnant Sprague-Dawley rats were exposed to poly(I: C) (4 mg/kg) or saline on gestational day 15, and the antioxidant n-acetylcysteine (NAC; 100 mg/kg) or saline 24 h before and after poly(I: C). Offspring had 24-hour access to 10% ethanol and water during adolescence. In adulthood, offspring were trained to self-administer 10% ethanol and tested on escalating schedules of reinforcement. Elevated plus maze (EPM) behavior was assessed on non-self-administration days.

RESULTS: Poly(I: C) and NAC treatment independently led to an increased willingness to work for alcohol in males, but not females, relative to same-sex controls. NAC treatment suppressed the MIA-induced increase in alcohol-seeking. Poly(I: C) increased locomotor activity in the EPM in both sexes, independent of NAC, without altering open or closed arm time.

CONCLUSIONS: These data support the hypothesis that MIA-induced oxidative stress negatively influences development, leaving the brain more susceptible to the negative effects of AA, and increasing the risk of alcohol misuse in adulthood, particularly in males.},
}

@article {pmid41482855,
year = {2026},
author = {Benna-Doyle, S and Grant, S and Maunder, A and Liu, J and Ibrahim, M and Cave, A and Pandey, C and Tang, M and Koh, ES and Delaney, G and Bhuyan, DJ and Choi, V and Kwon, K and Gonzalez, M and Graham, S and Malalasekera, A and Ee, C},
title = {The Efficacy and Safety of Nutritional Supplements for Cancer Supportive Care: An Umbrella Review and Hierarchical Evidence Synthesis.},
journal = {Integrative cancer therapies},
volume = {25},
number = {},
pages = {15347354251405267},
doi = {10.1177/15347354251405267},
pmid = {41482855},
issn = {1552-695X},
mesh = {Humans ; *Dietary Supplements/adverse effects ; *Neoplasms/therapy ; },
abstract = {Cancer survivors experience a range of side effects during and after treatment. There is a need for a rigorous synthesis of the most recent and best available evidence on the role of nutritional supplements for supportive care in cancer, to inform shared decision-making. We searched 5 databases for umbrella reviews, meta-analyses and systematic reviews on nutritional supplements for supportive cancer care, excluding studies on pain, anxiety and depression, which are covered in recent guidelines. We found 52 reviews that reported on 250 RCTs on 18 supplements for 16 indications. Almost all reviews were of low/critically low quality (assessed using A MeaSurement Tool to Assess systematic Reviews version 2). There was moderate-certainty evidence for benefit from the following supplements: amino acids and oral proteolytic enzymes for severity of radiation-induced dermatitis, N-acetyl cysteine for prevention of chemotherapy-induced peripheral neuropathy (CIPN) in individuals with gastrointestinal cancers. There was low to very low certainty evidence that glutamine, zinc, probiotics and melatonin may be effective for oral mucositis; Vitamin E, omega-3 fatty acids, glutamine and other amino acids may be effective for preventing CIPN. Serious adverse events were reported for high-dose Vitamin A, and dose-related adverse events were reported with zinc and Vitamin E. However, the majority of nutritional supplements were associated with only minor adverse events. Due to the low to very low certainty of the majority of evidence, firm clinical recommendations cannot be made. Further research to conclusively evaluate benefit and harm, including potential impact on efficacy of standard treatments, should be conducted.},
}

Humans
*Dietary Supplements/adverse effects
*Neoplasms/therapy

@article {pmid41479169,
year = {2026},
author = {Li, Z and Yang, X and Mao, J and Zeng, P and Qi, Y and Shi, Y and Guo, J and Zhou, J and Wang, D and Liu, J and Hou, L},
title = {Senecavirus a VP2 protein orchestrates PRDX1 degradation through dual autophagy pathways: macroautophagy and chaperone-mediated autophagy.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/15548627.2025.2610449},
pmid = {41479169},
issn = {1554-8635},
abstract = {Co-adaptation between viruses and autophagy has equipped viruses with diverse strategies to regulate host redox homeostasis, thereby facilitating viral replication. However, the mechanisms by which viruses manipulate PRDX1 (peroxiredoxin 1), a key antioxidative enzyme, via autophagy remain poorly understood. Here, we demonstrate that infection by Senecavirus A (SVA), an emerging picornavirus, induces PRDX1 degradation, and that PRDX1 negatively regulates viral replication. Decreased PRDX1 expression impairs cellular antioxidant defenses, leading to enhanced reactive oxygen species generation that facilitates SVA replication. Screening of viral proteins revealed that SVA VP1, VP2, and 3A induce PRDX1 degradation through vesicle formation-dependent macroautophagy. Notably, viral VP2 can also recruit HSPA8/HSC70 to specifically target PRDX1, directing it for degradation via LAMP2A-mediated chaperone-mediated autophagy (CMA). Collectively, these findings demonstrate that the SVA VP2 protein plays a central role in orchestrating both macroautophagy- and CMA-mediated PRDX1 degradation, establishing PRDX1 as a potential intervention target for countering SVA infection.Abbreviations: AKT/protein kinase B: AKT serine/threonine kinase; ATP: adenosine triphosphate; BHK-21: baby hamster kidney-21; CAT: catalase; CCCP: BMDMs: bone marrow-derived macrophages; CMA: chaperone-mediated autophagy; co-IP: co-immunoprecipitation; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CQ: chloroquine; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DMSO: dimethyl sulfoxide; GFP: green fluorescent protein; GPX: glutathione peroxidase; GSH: glutathione; HEK-293T: human embryonic kidney 293T; hpi: hours post-infection; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; KO: knockout; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; Mdivi-1: mitochondrial division inhibitor-1; mM: millimole; MMP: mitochondrial membrane potential; mPTP: mitochondrial permeability transition pore; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetylcysteine; PI3K: phosphoinositide 3-kinase; PRDX1: peroxiredoxin 1; RT-qPCR: real-time quantitative reverse transcription polymerase chain reaction; ROS: reactive oxygen species; SD: standard deviation; SOD: superoxide dismutase; SQSTM1: sequestosome 1; SVA: Senecavirus A; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; WT: wild-type; μg: microgram; μm: micrometer; μM: micromolar.},
}

@article {pmid41475676,
year = {2025},
author = {Eskafinoghani, A and Palomares, AR and Hao, X and Mohammadi, R and Lundberg, A and Rodriguez-Walberg, KA},
title = {Early gonadotoxic effects of cyclophosphamide on the prepubertal testis and the feasibility of reducing toxicity through combined antioxidant therapy.},
journal = {Reproductive toxicology (Elmsford, N.Y.)},
volume = {},
number = {},
pages = {109156},
doi = {10.1016/j.reprotox.2025.109156},
pmid = {41475676},
issn = {1873-1708},
abstract = {Early chemotherapy-induced gonad toxicity threatens future fertility in boys, yet early in-vivo testicular responses are poorly defined. To characterize acute effects of cyclophosphamide (CPA) on the prepubertal testis and explore whether combined antioxidants (AO; L-carnitine [LC] and N-acetyl cysteine [NAC]) modulate these changes. CBA/B6 F1 male pups (postnatal day 7-9) were randomized to saline control, CPA (100mg/kg i.p.), AO, or CPA+AO. Testes were collected every 8h to 48h for histology/immunostaining and were pooled (n=3 per group/time point) for bulk RNA-seq per group/time point. Histology showed emerging degeneration from ~32h with prominent effects by 48h after CPA, including reduced germ cell layers, increased γH2AX/CC3, and decreased Ki67. Transcriptionally, CPA perturbed apoptosis/developmental pathways as early as 16h, preceding overt histological change. AO and CPA+AO groups displayed partial transcriptional shifts toward control profiles, consistent with mitigation of CPA-associated signatures, but not full normalization. In neonatal mouse testis, CPA elicits rapid transcriptomic reprogramming within 16h, before morphological injury at ~32-48h. Concomitant AO shows preliminary, partial protective transcriptional effects. These proof-of-concept data support transcriptomics as an early, sensitive readout of testicular toxicity and motivate follow-up studies with independent validation and long-term outcomes prior to clinical translation.},
}

@article {pmid41472557,
year = {2025},
author = {Wu, QN and Feng, ZR and Tang, Q and Jin, JP and Liu, XH and Mai, ZB and Zhao, SN and Lan, YQ and Chen, KX and Lin, JD and Xu, PC and Fu, JJ},
title = {Redox-Active Cerium Oxide Nanoparticles Protect Against Acetaminophen-Induced Acute Liver Injury by Modulating Oxidative Stress and Inflammatory Pathways.},
journal = {Molecular pharmaceutics},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.molpharmaceut.5c01647},
pmid = {41472557},
issn = {1543-8392},
abstract = {Acute liver injury (ALI), often triggered by an acetaminophen (APAP) overdose, is characterized by severe oxidative stress, inflammation, and hepatocyte apoptosis. Current therapies, such as N-acetylcysteine (NAC), are limited by narrow treatment windows, highlighting the need for more effective antioxidant strategies. In this study, cerium oxide nanoparticles (CeO2 NPs, nanoceria) were synthesized and comprehensively characterized using the transmission electron microscopy (TEM), dynamic light scattering method (DLS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) to confirm their branched morphology, high crystallinity, and mixed Ce[3+]/Ce[4+] valence states. Their enzyme-mimetic antioxidant activities were evaluated through superoxide, hydrogen peroxide, and hydroxyl radical scavenging assays. Nanoceria exhibited excellent cytocompatibility and effectively suppressed the generation of lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) and lipid peroxidation and caspase-3-mediated apoptosis in macrophages. They also downregulated pro-inflammatory mediators (nitric oxide synthase (iNOS), TNF-α, IL-1β, and NLRP3) while enhancing anti-inflammatory markers (Arg1 and IL-10). In an APAP-induced ALI mouse model, nanoceria preferentially accumulated in the liver, alleviated oxidative stress and inflammation, and significantly reduced aspartate aminotransferase (AST) levels, showing hepatoprotective efficacy comparable to NAC. Nanoceria protect against APAP-induced ALI via synergistic antioxidative and anti-inflammatory mechanisms based on reversible Ce[3+]/Ce[4+] redox cycling. These findings underscore nanoceria's potential as a next-generation nanotherapeutic for oxidative stress-related liver diseases.},
}

@article {pmid41469142,
year = {2025},
author = {Wang, H and Fan, Y and Liang, Q and Tao, W and Chen, X and Wang, J and Cao, S and Ye, J and Zuo, S and Zhang, C and Shen, D and Gao, Y and Huang, Q and Ma, X and Zhang, X and Huang, Y and Yang, M},
title = {MAVS/CMTM6 axis couples mitochondrial homeostasis to immunogenic senescence via CCL3-driven T-cell recruitment in renal carcinoma.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {12},
pages = {},
doi = {10.1136/jitc-2025-011477},
pmid = {41469142},
issn = {2051-1426},
mesh = {Humans ; *Kidney Neoplasms/immunology/pathology/metabolism/genetics ; *Mitochondria/metabolism ; Animals ; Mice ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; *Carcinoma, Renal Cell/immunology/pathology/metabolism ; Cellular Senescence/immunology ; Homeostasis ; Female ; },
abstract = {BACKGROUND: Mitochondrial antiviral signaling protein (MAVS), a central adaptor in cytosolic RNA sensing, is critical for antitumor innate immunity and maintains mitochondrial homeostasis via its mitochondrial localization. Mitochondrial dysfunction acts as a key driver and amplifier of the senescence-associated secretory phenotype (SASP), a double-edged sword in tumor progression. However, whether tumor-intrinsic MAVS can regulate antitumor immunity via cellular senescence independently of its well-established interferon signaling remains unclear.

METHODS: Our study employed an integrated strategy. Clinically, we profiled MAVS expression and its association with prognosis and immune infiltration in renal tumor specimens. Mechanistic insights into tumor-intrinsic MAVS were gained through a battery of techniques spanning quantitative PCR, immunoblotting, RNA sequencing, senescence and mitochondrial function assays, confocal imaging, immunohistochemical, mass spectrometry, and co-immunoprecipitation. In vivo, we used MAVS-deficient models combined with CD8[+] T-cell depletion, programmed cell death protein-1 (PD-1) blockade, or reactive oxygen species (ROS) scavenging by N-acetylcysteine (NAC), with immune infiltration characterized by flow cytometry.

RESULTS: Clinical evidence links elevated MAVS expression in renal tumors to poor prognosis and diminished CD8[+] T-cell infiltration. Strikingly, tumor-intrinsic MAVS deficiency curbed malignant progression by triggering cellular senescence and fostering a permissive niche for CD8[+] T-cell activation and recruitment. Mechanistically, MAVS orchestrates mitochondrial integrity by co-localizing with and stabilizing chemokine-like factor-like MARVEL transmembrane domain-containing 6 (CMTM6), thereby shielding it from lysosomal degradation. Disruption of this axis provoked mitochondrial dysfunction and ROS accumulation, culminating in senescence and an SASP marked by chemokine C-C motif ligand 3 (CCL3). Thus, despite dampening canonical innate immune signaling, MAVS deletion unleashed potent antitumor immunity via CCL3-mediated CD8[+] T-cell recruitment, an effect abolished by CD8[+] T-cell depletion or ROS scavenging with NAC. Leveraging this paradigm, we demonstrated that tumor-specific MAVS deficiency acts synergistically with PD-1 blockade to achieve robust therapeutic efficacy.

CONCLUSIONS: Our findings establish the tumor-intrinsic MAVS/CMTM6/CCL3 axis as a previously unrecognized critical regulator of senescence-driven antitumor immunity in renal carcinoma. Therapeutic targeting of this axis presents a promising strategy to curtail tumor progression and potentiate immunotherapy.},
}

Humans
*Kidney Neoplasms/immunology/pathology/metabolism/genetics
*Mitochondria/metabolism
Animals
Mice
*Adaptor Proteins, Signal Transducing/metabolism/genetics
*Carcinoma, Renal Cell/immunology/pathology/metabolism
Cellular Senescence/immunology
Homeostasis
Female

@article {pmid41467082,
year = {2025},
author = {Wolie, AA and Mengistie, BT and Mengistie, CT and Genet, A and Wakie, SA and Alebachew, EA and Bonus, SM},
title = {Overlapping Hepatic and Neurological Toxicity Following Intentional Multidrug Poisoning with Acetaminophen, Metoclopramide, and Metronidazole: A Case Report.},
journal = {Clinical medicine insights. Case reports},
volume = {18},
number = {},
pages = {11795476251410404},
doi = {10.1177/11795476251410404},
pmid = {41467082},
issn = {1179-5476},
abstract = {INTRODUCTION: Polydrug overdose, defined as the simultaneous ingestion of multiple toxic substances, is increasingly encountered in emergency departments. Overlapping toxidromes often obscure the causative agents, complicating diagnosis and management. Acetaminophen (APAP) overdose can cause hepatotoxicity through N-acetyl-p-benzoquinone imine (NAPQI) formation, metoclopramide may precipitate acute extrapyramidal symptoms, and metronidazole can induce neurotoxicity, typically a cerebellar syndrome.

CASE SUMMARY: Young adult male medical student intentionally ingested 12 g of APAP, 170 mg of metoclopramide, and 8 g of metronidazole. He presented 24 hours later with repeated vomiting, tremor, rigidity, dysarthria, gait ataxia, and transient confusion. Vital signs were stable; laboratory tests showed transaminase elevation and coagulopathy. Peak AST/ALT were 100/76 U/L and INR peaked at 1.74. Management included oral N-acetylcysteine for APAP toxicity, intravenous diphenhydramine and diazepam for extrapyramidal symptoms, supportive ICU care, and psychiatric intervention. Coagulopathy was corrected with fresh frozen plasma. Neurological and hepatic abnormalities resolved within 72 hours, and the patient remained asymptomatic at 2-week follow-up. The patient recovered fully after N-acetylcysteine and supportive care, illustrating the diagnostic challenges of overlapping toxidromes.

CONCLUSION: This case highlights the diagnostic and therapeutic challenges of polydrug overdose with overlapping toxidromes. Rapid identification and agent-specific management, including NAC for APAP, symptomatic therapy for metoclopramide and metronidazole toxicity, and supportive care, resulted in full recovery without long-term sequelae. Emergency clinicians should maintain high suspicion for multiple co-ingestants and use targeted interventions to optimize outcomes.},
}

@article {pmid41462060,
year = {2025},
author = {Kim, JW and Won, HR and Kim, CS and Choi, JS and Woo, SH and Lee, DW and Kwon, M and Joo, YH and Koo, BS and Cho, KJ},
title = {Effects of topically applied liquid N-acetylcysteine for the management of burning mouth syndrome.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {44889},
pmid = {41462060},
issn = {2045-2322},
mesh = {Humans ; *Acetylcysteine/administration & dosage/therapeutic use ; *Burning Mouth Syndrome/drug therapy ; Male ; Female ; Aged ; Middle Aged ; Administration, Topical ; Quality of Life ; Prospective Studies ; Clonazepam/administration & dosage/therapeutic use ; Treatment Outcome ; Pain Measurement ; Adult ; },
abstract = {Burning Mouth Syndrome (BMS) is a chronic neuropathic pain condition with limited treatment options. N-acetylcysteine (NAC), a thiol-based antioxidant with neuroprotective properties, has not been clinically evaluated as a topical agent for BMS. This study aimed to evaluate the efficacy of topically applied liquid NAC in reducing symptoms and improving quality of life of patients with BMS. In a multicenter, prospective, nonrandomized, open-label study, 114 patients with BMS were allocated to receive liquid NAC oral rinse, oral clonazepam, or combination therapy for eight weeks. Symptoms were assessed at baseline, week 4, and week 8 using the visual analog scale (VAS) and the Korean version of the Oral Health Impact Profile-14 (OHIP-14 K). Across all three groups, VAS scores declined significantly within groups from baseline to week 4 and to week 8; however, the magnitude of VAS change did not differ between groups at either time point. For OHIP‑14 K, significant within‑group decreases were observed in the liquid NAC and combination groups from baseline to weeks 4 and 8, whereas the clonazepam group showed a significant decrease only from week 4 to week 8 and not from baseline. At week 4, the combination group achieved a larger OHIP‑14 K reduction than either monotherapy; by week 8, between‑group differences were no longer significant. Topically applied liquid NAC, alone or in combination with clonazepam, effectively reduced pain and enhanced patient-reported outcomes. These findings support the potential of a localized and safe strategy targeting neuropathic mechanisms in BMS. Topically administered liquid NAC demonstrates potential as an effective and well-tolerated therapeutic strategy for managing BMS, offering symptom relief with minimal systemic burden. Although the combination with clonazepam did not demonstrate sustained superiority at 8 weeks, its principal advantage is a faster onset of improvement in OHIP‑14 K, evident by week 4.},
}

Humans
*Acetylcysteine/administration & dosage/therapeutic use
*Burning Mouth Syndrome/drug therapy
Male
Female
Aged
Middle Aged
Administration, Topical
Quality of Life
Prospective Studies
Clonazepam/administration & dosage/therapeutic use
Treatment Outcome
Pain Measurement
Adult

@article {pmid41460361,
year = {2025},
author = {Yang, CW and Yen, CH and Chien, TM and Yu, SY and Chang, FR and Sheu, JH and Chang, HW},
title = {Excavatolide E triggers oxidative stress-associated apoptosis and DNA damage to inhibit bladder cancer cell proliferation.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {234},
pmid = {41460361},
issn = {1573-4978},
support = {NSTC 114-2314-B-037-032//National Science and Technology Council/ ; NSTC 114-2320-B-037-015//National Science and Technology Council/ ; KMU-DK(A)113003 and KMU-TB114009//Kaohsiung Medical University/ ; KMU-TC114A04//Kaohsiung Medical University Research Center/ ; },
mesh = {Humans ; *Oxidative Stress/drug effects ; *Apoptosis/drug effects ; *Urinary Bladder Neoplasms/drug therapy/metabolism/genetics/pathology ; Cell Proliferation/drug effects ; *DNA Damage/drug effects ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Cell Survival/drug effects ; Animals ; Mitochondria/drug effects/metabolism ; Anthozoa/chemistry ; },
abstract = {BACKGROUND: Excavatolide E (EXCE), a biocompound extracted from the gorgonian octocoral Briareum excavatum, has received limited attention for its anticancer properties, especially in the context of bladder cancer.

METHODS: Cell viability, flow cytometry, and Western blotting were performed to assess the antiproliferative effects and mechanisms against bladder cancer cells.

RESULTS: In the present study, the impacts and mechanisms of EXCE's antiproliferative effects on bladder cancer cells were assessed, along with its impacts on normal cells. EXCE selectively inhibited proliferation of bladder cancer cells, as compared to normal cells, i.e., selectivity index > 2, and induced greater oxidative stress in bladder cancer cells than normal cells, regarding the induction of cellular and mitochondrial ROS, as well as the depletion of mitochondrial membrane potential. Moreover, EXCE triggered higher levels of apoptosis, both extrinsic and intrinsic caspase activation, and DNA damage in bladder cancer cells than in normal cell; these EXCE-triggered antiproliferative mechanisms were alleviated by N-acetylcysteine (NAC), a ROS inhibitor.

CONCLUSION: Therefore, EXCE's antiproliferative activity offers a promising therapeutic approach for targeting bladder cancer cells by modulating oxidative stress, while preserving the safety of normal cells.},
}

Humans
*Oxidative Stress/drug effects
*Apoptosis/drug effects
*Urinary Bladder Neoplasms/drug therapy/metabolism/genetics/pathology
Cell Proliferation/drug effects
*DNA Damage/drug effects
Cell Line, Tumor
Reactive Oxygen Species/metabolism
Membrane Potential, Mitochondrial/drug effects
Cell Survival/drug effects
Animals
Mitochondria/drug effects/metabolism
Anthozoa/chemistry

@article {pmid41458194,
year = {2026},
author = {Alajab, MB and Elameen, SAO and Mohamed, FAY and Eisa, MGM and Omer, EOM and Elmubarak, MAH and Elmubarak, MAH and Abdalazim Dafallah, M},
title = {Fulminant Hepatic Failure in Dengue Infection: Two Survivors From a Resource-Limited Outbreak in Sudan.},
journal = {Clinical case reports},
volume = {14},
number = {1},
pages = {e71721},
pmid = {41458194},
issn = {2050-0904},
abstract = {Dengue is a leading cause of viral hemorrhagic fever globally, with hepatic involvement being common but usually mild. Rarely, dengue can progress to fulminant hepatic failure, a life-threatening complication requiring prompt recognition especially in resource-limited settings. We report two Sudanese male patients (aged 29 and 18) who presented with jaundice, markedly elevated liver enzymes, hepatic encephalopathy, and coagulopathy. Both fulfilled criteria for fulminant hepatic failure with hepatic encephalopathy. One patient had concurrent hepatitis B infection and developed acute kidney injury requiring hemodialysis. Both patients received supportive management including intravenous N-acetylcysteine, correction of coagulopathy, glucose infusion, hypertonic saline, lactulose/rifaximin, and appropriate transfusions. Renal replacement therapy was initiated in the patient with acute kidney injury. Despite severe presentation and limited resources, both patients demonstrated progressive clinical and biochemical improvement. Follow-up showed complete recovery of liver and renal parameters. These cases underscore that early recognition and intensive supportive management, including N-acetylcysteine, are critical for survival in dengue-associated fulminant hepatic failure, even in constrained settings.},
}

@article {pmid41452363,
year = {2025},
author = {Chen, Y and Wu, W and Zhao, L and Shen, L and Tao, D and Liang, Y and Zheng, X and Zheng, Z and Luo, C and Peng, F and Chen, X and Long, H},
title = {GATA1 controls metadherin transcription to promote oxidative stress-induced podocyte injury.},
journal = {Journal of molecular medicine (Berlin, Germany)},
volume = {104},
number = {1},
pages = {14},
pmid = {41452363},
issn = {1432-1440},
support = {82000682//National Natural Science Foundation of China/ ; 82374198//National Natural Science Foundation of China/ ; 82570842//National Natural Science Foundation of China/ ; 2024A1515030266//Basic and Applied Basic Research Foundation of Guangdong Province/ ; yzjj2022ms01//President Foundation of Zhujiang Hospital, Southern Medical University/ ; 2021XM08//Science and Technology Action of Erdos High-tech Industrial Development Commission of Inner Mongolia/ ; },
mesh = {*Podocytes/metabolism/pathology ; *Oxidative Stress ; Animals ; RNA-Binding Proteins/genetics ; Mice ; *Membrane Proteins/genetics/metabolism ; *Renal Insufficiency, Chronic/metabolism/pathology/genetics ; *GATA1 Transcription Factor/metabolism/genetics ; beta Catenin/metabolism ; Male ; Humans ; Advanced Oxidation Protein Products ; *Transcription, Genetic ; Mice, Inbred C57BL ; *Cell Adhesion Molecules/genetics/metabolism ; Signal Transduction ; Gene Expression Regulation ; },
abstract = {Oxidative stress has been demonstrated to induce damage to podocytes, which play a pivotal role in the pathogenesis of chronic kidney disease (CKD). Metadherin (MTDH), an oncogene that has been extensively investigated in various malignancies, also contributes to podocyte injury in CKD. However, the relationship between oxidative stress and MTDH remains poorly elucidated. Here, we show that elevated oxidative stress in CKD serum induced MTDH expression and activated β-catenin signaling in podocytes, which were reversed by N-acetyl cysteine (NAC), a pharmacological antioxidant agent. Therefore, we established the oxidative stress model by administration of Advanced Oxidation Protein Products (AOPPs). As for the mechanism, oxidative stress enhanced MTDH expression both in mRNA and protein levels in podocytes. Furthermore, transcription factor prediction analysis and the Chip-qPCR assay identified that GATA1 was capable of directly binding to the MTDH promoter following AOPP stimulation. Silencing GATA1 repressed MTDH expression induced by AOPPs, while overexpressing GATA1 enhanced MTDH expression and subsequently activated β-catenin signaling. In conclusion, GATA1 induced by oxidative stress triggers MTDH transcription to activate β-catenin signaling, thereby promoting podocyte injury. Thus, targeting the GATA1/MTDH axis may present a promising therapeutic strategy for attenuating oxidative stress-induced damage in podocytes during CKD. KEY MESSAGES: Advanced Oxidative Protein Products (AOPPs) promote the accumulation of oxidative stress in circulation Metadherin is elevated in kidneys of AOPP-induced oxidative stress CKD model mice GATA1 controls transcription of MTDH in renal podocyte of CKD Silencing GATA1/MTDH axis interrupts β-catenin signaling and ameliorates podocyte injury and CKD pathology.},
}

*Podocytes/metabolism/pathology
*Oxidative Stress
Animals
RNA-Binding Proteins/genetics
Mice
*Membrane Proteins/genetics/metabolism
*Renal Insufficiency, Chronic/metabolism/pathology/genetics
*GATA1 Transcription Factor/metabolism/genetics
beta Catenin/metabolism
Male
Humans
Advanced Oxidation Protein Products
*Transcription, Genetic
Mice, Inbred C57BL
*Cell Adhesion Molecules/genetics/metabolism
Signal Transduction
Gene Expression Regulation

@article {pmid41446880,
year = {2025},
author = {van Brummelen, R and van Brummelen, AC},
title = {The role of neuro-supportive substances of natural origin in neurological conditions-A literature-based formulators' perspective.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1647092},
pmid = {41446880},
issn = {1664-2295},
abstract = {Products of natural origin are seldom tested up to a point of full acceptance, mainly due to a lack of financial viability for commercialization. Yet many come with a rich history of use and proof of concept testing. We investigated literature regarding the possible role and function of the best known of these nutraceuticals in relationship to three neurological conditions i.e. stroke, Alzheimer's - (AD) and Parkinson's disease (PD), and their potential as supportive therapies. Current studies suggest that citicoline has a neuroprotective effect in ischemic conditions, playing a role in the restoration of the barrier function of endothelial cells, activating repair mechanisms and possibly decreasing ischemic lesion size in stroke, as well as increasing dopamine availability in PD. Citicoline was also demonstrated to increase the levels of sirtuin 1 (SIRT1), thus reducing inflammation-leading to improved cognitive status and a better quality of life in cognitive impairment. N-Acetylcysteine (NAC) shows pro-cognitive effects, increasing glutathione (GSH) levels that are decreased in AD and PD patients, possibly decreasing neuroinflammation. Mechanistic studies indicate the potential neuroprotective and neurorestorative effects of resveratrol by its anti-inflammatory and anti-apoptotic activity, also increasing SIRT1 levels and promoting the outgrowth of neurite protrusions and synaptogenesis. Curcumin's anti-inflammatory effects via inhibition of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can potentially delay progression of PD. Some nutraceuticals, e.g., citicoline, show synergism in combination with current therapies. We propose a renewed, risk-benefit approach for inclusion of the investigated nutraceuticals with limited indications in certain neurological treatment regimens.},
}

@article {pmid41445121,
year = {2025},
author = {Mehrpour, O and Soltani, M and Karami-Mohajeri, S and Khanamani Falahatipour, S},
title = {Acetaminophen poisoning: contemporary intravenous acetylcysteine regimens and early discharge pathways.},
journal = {Expert opinion on pharmacotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14656566.2025.2610370},
pmid = {41445121},
issn = {1744-7666},
abstract = {INTRODUCTION: Acetaminophen (paracetamol, APAP) overdose remains a leading cause of drug-induced acute liver failure, yet N-acetylcysteine (NAC) prevents hepatic injury.

AREAS COVERED: We conducted a narrative search of PubMed/MEDLINE, Embase, and Google Scholar (January 2000-August 2025) and reviewed NAC regimens, including the 3-bag protocol (21 h), the U.S. FDA-labeled 2-bag regimen (20 h), and the 12-h Scottish and Newcastle Acetylcysteine Protocol (SNAP), as well as early-stop pathways. Across regimens, efficacy is broadly similar, but simplified protocols reduce non non-immunoglobulin E reactions and dosing errors. SNAP delivers 300 mg/kg over 12 h and is extended only when stopping criteria are not met, whereas early-stop pathways (NACSTOP/SARPO) are restricted to selected low-risk patients. In most acute overdoses, NAC can be stopped when APAP is < 10 mg/L, ALT/AST are stable or falling, and INR is acceptable.

EXPERT OPINION: A protocolized NAC pathway with clear stop/extend rules is the most impactful way to improve care. Escalation (higher or prolonged dosing, early hepatology/transplant referral, and consideration of ECTR) should be reserved for high-risk cases. In low- and middle-income countries (LMICs), dose and timing history can guide empiric NAC when levels are delayed. Biomarkers and artificial intelligence remain useful adjuncts, not substitutes, for laboratory-based decisions.},
}

@article {pmid41441921,
year = {2025},
author = {Yavuz, M and Acer, S and Celik, O and Argun, M and Ozmen, O and Tok, L},
title = {Assessment of neuroprotective efficacy of N-acetylcysteine compared with brimonidine in an experimental glaucoma model.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {53},
pmid = {41441921},
issn = {1573-2630},
mesh = {Animals ; *Brimonidine Tartrate/therapeutic use ; Female ; Rats ; Disease Models, Animal ; Rats, Wistar ; *Glaucoma/drug therapy/metabolism/pathology ; *Neuroprotective Agents/therapeutic use ; *Acetylcysteine/therapeutic use/pharmacology ; Retinal Ganglion Cells/pathology/drug effects ; Oxidative Stress/drug effects ; Apoptosis/drug effects ; Intraocular Pressure/drug effects ; Adrenergic alpha-2 Receptor Agonists ; },
abstract = {PURPOSE: To investigate the neuroprotective effects of N-acetylcysteine (NAC) in comparison with brimonidine in an experimental glaucoma model.

METHODS: Thirty-two adult female Wistar albino rats were randomly assigned to five groups: Control, Sham, NAC, Brimonidine, and Combination (NAC + Brimonidine). Glaucoma was induced in the right eye by optic nerve crush in all groups except Control. Treatments were administered intraperitoneally every 72 h for 30 days. Neuroprotection was assessed histopathologically by measuring ganglion cell layer (GCL) thickness and total retinal thickness. Apoptotic activity and glial activation were evaluated by quantifying B-cell lymphoma/leukemia-2 (BCL-2), BCL-2-associated X protein (BAX) and glial fibrillary acidic protein (GFAP) expression. Oxidative stress and antioxidant capacity were assessed using malondialdehyde (MDA), total oxidant status (TOS), glutathione (GSH) and total antioxidant capacity (TAC) levels.

RESULTS: NAC significantly preserved GCL and total retinal thickness compared with the Sham group (P < 0.001), with neuroprotective efficacy comparable to brimonidine (P > 0.05). The combination therapy group demonstrated the most pronounced neuroprotective effects. NAC treatment increased antiapoptotic BCL-2 and GSH levels while reducing BAX, GFAP, MDA, and TOS levels (P < 0.001).

CONCLUSIONS: NAC exhibited substantial neuroprotective effects in an intraocular pressure-independent glaucoma model, likely mediated through its antioxidant properties and modulation of apoptotic pathways. These findings suggest that NAC may serve as a promising adjunctive therapy for glaucomatous optic neuropathy and other retinal neurodegenerative disorders characterized by oxidative stress and apoptosis.},
}

Animals
*Brimonidine Tartrate/therapeutic use
Female
Rats
Disease Models, Animal
Rats, Wistar
*Glaucoma/drug therapy/metabolism/pathology
*Neuroprotective Agents/therapeutic use
*Acetylcysteine/therapeutic use/pharmacology
Retinal Ganglion Cells/pathology/drug effects
Oxidative Stress/drug effects
Apoptosis/drug effects
Intraocular Pressure/drug effects
Adrenergic alpha-2 Receptor Agonists

@article {pmid41440725,
year = {2025},
author = {Hong, M and Kedeshian, K and Hoffman, L and Kita, A},
title = {Preliminary Evaluation of an Injectable Therapeutic for Cisplatin Ototoxicity Using Neuronal SH-SY5Y Cells.},
journal = {Medicines (Basel, Switzerland)},
volume = {12},
number = {4},
pages = {},
pmid = {41440725},
issn = {2305-6320},
support = {K08 DC019957/DC/NIDCD NIH HHS/United States ; 1K08DC019957-01/NH/NIH HHS/United States ; Not applicable//American Neurotology Society/ ; },
abstract = {BACKGROUND/OBJECTIVES: Though ototoxic, cisplatin is a mainstay of chemotherapy for a variety of cancers. One suggested mechanism of cisplatin ototoxicity involves damage to the spiral ganglion afferent neurons in the inner ear. There is a need for a high-throughput model to screen medications for efficacy against cisplatin and to develop a local therapeutic to mitigate cisplatin's debilitating side effects. Microparticles encapsulating a therapeutic medication are an injectable and tunable method of sustained drug delivery, and thus a promising treatment.

METHODS: SH-SY5y human neuroblastoma cells were used as a cell line model for the spiral ganglion neurons. The cells were dosed with cisplatin and four potential therapeutics (melatonin, metformin, cyclosporine, and N-acetylcysteine), with cell viability measured by CCK-8 assay. The most promising therapeutic, N-acetylcysteine (NAC), was then encapsulated into multiple poly(lactic-co-glycolic acid) (PLGA) microparticle subtypes of varied lactide-glycolide (L:G) ratios and NAC amounts. The elution profile of each microparticle subtype was determined over two months.

RESULTS: Of the therapeutics screened, only cells dosed with 1 or 10 mM NAC prior to cisplatin injury demonstrated an improvement in cell viability (73.8%, p < 1 × 10[-8]) when compared to cells dosed with cisplatin alone. The 75:25 L:G microparticles demonstrated an increase in the amount of NAC released compared to the 50:50 L:G microparticles.

CONCLUSIONS: NAC is a potential therapeutic agent for cisplatin toxicity when tested in a neuronal cell line model. NAC was encapsulated into PLGA microparticles and eluted detectable concentrations of NAC for 6 days, which is a first step towards otoprotection for the weeks long duration of chemotherapy treatment. This work describes a method of screening potential therapeutics and a strategy to develop local drug eluting treatments to protect against cisplatin ototoxicity.},
}

@article {pmid41440550,
year = {2025},
author = {Parpoudi, S and Mantzoros, I and Ioannidis, O and Zapsalis, K and Gamali, T and Kyziridis, D and Gekas, C and Anestiadou, E and Symeonidis, S and Bitsianis, S and Kotidis, E and Pramateftakis, MG and Miliaras, D and Bikouli, A and Iosifidis, G and Angelopoulos, S},
title = {Effect of N-Acetyl-L-Cysteine (NAC) on Inflammation After Intraperitoneal Mesh Placement in an Escherichia coli Septic Rat Model: A Randomized Experimental Study.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {41440550},
issn = {2076-3271},
mesh = {Animals ; *Acetylcysteine/pharmacology/therapeutic use ; *Escherichia coli/drug effects ; *Surgical Mesh/adverse effects ; Rats ; *Escherichia coli Infections/drug therapy ; Disease Models, Animal ; *Inflammation/drug therapy/etiology ; *Sepsis/drug therapy/microbiology ; Male ; Tissue Adhesions ; Cytokines/blood ; },
abstract = {Background/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to determine whether NAC reduces mesh-related inflammation in a septic model created by intraperitoneal Escherichia coli (E.coli) inoculation. The primary comparison was prospectively defined between E. coli-inoculated animals treated with NAC (D) and those without NAC (B). Groups without E. coli (A,C,E) are presented for context and were compared previously. Methods: In this randomized, double-blind experimental model (five groups, n = 20 per group), all rats underwent midline laparotomy with intraperitoneal placement of a composite mesh, followed by standardized ciprofloxacin administration. The septic groups received intraperitoneal E. coli, while the NAC-treated groups additionally received intraperitoneal NAC (150 mg/kg). Serum levels of IL-1α, IL-6, and TNF-α were measured on postoperative days 7, 14, and 21. On day 21, adhesions were graded using the Modified Diamond system, histology (inflammatory infiltration, fibrosis, neovascularization) was scored, and mesh cultures were obtained. Cytokine data were analyzed with repeated-measures ANOVA, while categorical or ordinal outcomes were assessed using χ[2] or Fisher's exact tests with Bonferroni-adjusted pairwise comparisons. Results: E. coli inoculation significantly increased adhesion burden and worsened histologic scores compared with controls (both p < 0.001). NAC administration in the septic model significantly reduced adhesions and improved all histologic domains relative to E. coli alone (all p ≤ 0.003), with values comparable to controls (non-significant across domains). For cytokines, there was a significant overall group effect for IL-1α, IL-6, and TNF-α (all p < 0.001), without a main effect of time or time × group interaction. Pairwise contrasts showed lower IL-1α (p = 0.024), IL-6 (p < 0.001), and TNF-α (p < 0.001) levels in group D versus B, and lower IL-6 and TNF-α in group D versus A (both p < 0.001). Mesh culture positivity rate was higher in group B than A (p < 0.001) and showed a non-significant reduction in group D versus B (p = 0.10). No perioperative deaths occurred. Conclusions: NAC attenuated septic, mesh-associated inflammation-normalizing adhesions and histology and reducing IL-6 and TNF-α- supporting its role as a host-directed adjunct alongside antibiotics. Further translational studies are warranted to define the optimal dose, timing, and clinical indications.},
}

Animals
*Acetylcysteine/pharmacology/therapeutic use
*Escherichia coli/drug effects
*Surgical Mesh/adverse effects
Rats
*Escherichia coli Infections/drug therapy
Disease Models, Animal
*Inflammation/drug therapy/etiology
*Sepsis/drug therapy/microbiology
Male
Tissue Adhesions
Cytokines/blood

@article {pmid41440263,
year = {2025},
author = {Liu, Z and Li, X and Liu, S and Cai, Y and Xu, X and Gao, S and Yao, C and Wang, L and Xie, X and Cai, Y and Jiang, L and Liu, J and Li, M and Li, Y and Huang, X and Chen, H},
title = {Transcriptomic Evaluation of Hollow Microneedles-Mediated Drug Delivery for Rheumatoid Arthritis Therapy.},
journal = {Biosensors},
volume = {15},
number = {12},
pages = {},
pmid = {41440263},
issn = {2079-6374},
support = {32171456, 82100430//National Natural Science Foundation of China/ ; 2024YFB3211600//National Key R&D Program of China/ ; 2023A1515111139, 2025A1515010608, 2020A1515111139//Guangdong Basic and Applied Basic Research Foundation/ ; 2024B03J0121, 2024B03J1284//Science and Technology Program of Guangzhou, China/ ; 2023A03J1008//Science and Technology Projects in Guangzhou/ ; 24xkjc011//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; 2024-skllmd-11//Open Fund of the State Key Laboratory of Luminescent Materials and Devices (South China University of Technology)/ ; JCYJ20220818102201003//Shenzhen Science and Technology Program/ ; },
mesh = {*Arthritis, Rheumatoid/drug therapy ; *Drug Delivery Systems/methods ; Animals ; Needles ; *Transcriptome ; Pyrimidines/administration & dosage/therapeutic use ; Piperidines/administration & dosage/therapeutic use ; Acetylcysteine/administration & dosage ; Humans ; Pyrroles/administration & dosage ; Gene Expression Profiling ; },
abstract = {Microneedle array-based drug delivery offers a minimally invasive and safe approach for breaching the skin barrier, enabling localized and targeted treatment-an advantage particularly valuable in chronic condition management, such as rheumatoid arthritis (RA). RA presents a multifaceted pathophysiology, often necessitating long-term pharmacological management. However, conventional oral administration may lead to systemic drug distribution, increasing the likelihood of adverse effects, and ultimately undermining therapeutic efficacy. In this study, a hollow microneedle array was employed for effective delivery of Tofacitinib and the antioxidant N-acetylcysteine (NAC). A comprehensive evaluation was conducted across multiple levels, in which inflammation and cartilage degradation were assessed histologically using hematoxylin-eosin (H&E) and Safranin O-Fast Green staining. Radiologically, micro-computed tomography (micro-CT) was employed to visualize bone structure alterations. On the molecular level, enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokines and oxidative stress markers. Furthermore, differentially expressed genes and enriched signaling pathways were identified through transcriptomic profiling pre- and post-treatment. And the potential regulatory targets and mechanistic insights into the therapeutic response were elucidated through correlation analyses between gene expression profiles and pathological indicators. This study provides a mechanistic and computational basis for precision targeted therapy, validates the efficacy and safety of microneedle delivery in a rheumatoid arthritis (RA) model, and demonstrates its potential application in local drug delivery strategies.},
}

*Arthritis, Rheumatoid/drug therapy
*Drug Delivery Systems/methods
Animals
Needles
*Transcriptome
Pyrimidines/administration & dosage/therapeutic use
Piperidines/administration & dosage/therapeutic use
Acetylcysteine/administration & dosage
Humans
Pyrroles/administration & dosage
Gene Expression Profiling

@article {pmid41440136,
year = {2025},
author = {Mulè, S and Parini, F and Galla, R and Uberti, F},
title = {Neuroinflammation-Modulating Properties Combining Glutathione, N-Acetylcysteine, and Uridine Monophosphate in a Formulation Supplement: An In Vitro Study.},
journal = {Brain sciences},
volume = {15},
number = {12},
pages = {},
pmid = {41440136},
issn = {2076-3425},
abstract = {Background: Neuropathic pain is a complex condition often resistant to current therapies due to limited efficacy and adverse effects. Nutraceuticals offer promising alternatives, combining antioxidant and anti-inflammatory properties with good tolerability. This study aimed to compare the effects of a commercial nutraceutical formulation, SUPERALA CARNITINE[®] (Pharma Suisse Laboratories SpA, Milan, Italy), containing Alpha-Lipoic Acid (ALA), with a novel formulation, called SUPERALA CARNITINE[®] Forte, where ALA and vitamin B6 were replaced by N-acetylcysteine (NAC), Glutathione (GSH), and Uridine monophosphate (UMP). Methods: An indirect gut-peripheral nerve axis was employed to simulate oral absorption, metabolism, and effect on nervous tissues using 3D in vitro models. Both formulations and their individual components were assessed for cytotoxicity and permeability in the gut model (Caco-2 cells in Transwell[®]) and, after gut metabolism, for antioxidant capacity, anti-inflammatory activity, and neuroprotective potential in the peripheral nerve model. Results: SUPERALA CARNITINE[®] Forte improved cell viability and favoured the maintenance of intestinal integrity, showing enhanced permeability, and significantly reduced oxidative stress (OS) and pro-inflammatory cytokines (TNF-α, IL-2) at the peripheral nervous system. In addition, it increased levels of neuronal markers (p75, MPZ, NRG1, ERβ) and decreased NaV1.7 and NaV1.8 activity, indicating greater neuroprotection and analgesic modulation than the ALA-based formula. Conclusions: The replacement of ALA and vitamin B6 with NAC, GSH, and UMP produced favorable responses in vitro on neuronal cells, supporting a hypothetical potential interest in this nutraceutical combination and justifying further future in vivo investigations.},
}

@article {pmid41431629,
year = {2025},
author = {Sinaeinejad, M and Karimi, M and Razavizadeh, M and Arj, A and Tabatabaei, SH and Mortezazadeh, M and Shirsalimi, N and Pirzad, S and Mofidi, A and Kashani, M},
title = {Efficacy of N-Acetylcysteine on Liver Function and Metabolic Profiles in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Double-Blind, Randomized Controlled Trial.},
journal = {Addiction & health},
volume = {17},
number = {},
pages = {1667},
pmid = {41431629},
issn = {2008-4633},
abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disorder associated with metabolic abnormalities. This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) in improving liver function and metabolic profile in patients with MASLD.

METHODS: In this randomized controlled trial (RCT), 69 patients with MASLD were randomly assigned to either the NAC group (600 mg, administered three times daily, n=34) or the placebo group (n=35) for eight weeks. The severity of hepatic steatosis, liver enzymes, and metabolic profile were measured at baseline and the final trial. Data were analyzed using SPSS.

FINDINGS: Following eight weeks of NAC administration in patients with MASLD, no significant changes were observed compared to the placebo in hepatic steatosis grade (P=0.215), serum aspartate aminotransferase (AST) (P=0.21), alanine transaminase (ALT) (P=0.28), malondialdehyde (MDA) (P=0.79), total antioxidant capacity (TAC) (P=0.56), triglycerides (P=0.15), total cholesterol (P=0.28), low-density lipoprotein cholesterol (P=0.32), and high-density lipoprotein cholesterol (P=0.16). However, NAC administration resulted in significant reductions in fasting blood glucose (FBG) (P=0.01), fasting insulin levels (P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (P<0.001), and C-reactive protein (CRP) (P<0.001), along with a significant increase in total glutathione levels (P=0.003), compared to the placebo group.

CONCLUSION: NAC administration in patients with MASLD does not significantly impact hepatic steatosis, liver enzymes, or lipid profiles; however, it improves oxidative, glycemic, and inflammatory markers. Therefore, NAC may be a beneficial adjunct therapy for managing metabolic parameters and reducing inflammation and oxidative stress in MASLD patients.

TRIAL REGISTRATION: The trial was registered with the Iranian Registry of Clinical Trials (IRCT20201220049772N1) on February 20, 2021.},
}

@article {pmid41428714,
year = {2025},
author = {Rocha, MBM and Assis, EIT and Azevedo, VAN and Lima Neto, MF and Silva, AWB and Godinho, AN and Freire, JMO and Félix, EDS and Ribeiro, RP and Gomes, GA and Silva, JRV},
title = {Piperine protects ovarian follicles and stromal cells against doxorubicin-induced adverse effects in mouse ovaries.},
journal = {JBRA assisted reproduction},
volume = {},
number = {},
pages = {},
doi = {10.5935/1518-0557.20250187},
pmid = {41428714},
issn = {1518-0557},
abstract = {OBJECTIVE: This study investigates the effects of Piperine (PIP) on doxorubicin (DOX)-induced changes in mouse ovarian follicles, stromal cells, collagen fibers, and mRNA expression of nuclear factor erythroid 2-related factor (NRF2), superoxide dismutase (SOD), and catalase (CAT).

METHODS: The mice were randomly divided into seven groups. In the first three groups, they received saline (1), both DOX and N-acetylcysteine (2), or DOX only (3). In groups 4 and 5, mice were treated with DOX in combination with 0.1 or 10.0mg/kg PIP. In groups 6 and 7, mice received 0.1 or 10.0mg/kg PIP alone. After 10 days, ovaries were collected and used to evaluate follicular morphology and growth, collagen fibers, stromal cells, and mRNA for NRF2, SOD, and CAT.

RESULTS: Mice treated with DOX showed reduced percentage of normal follicles, but the combination of DOX with PIP or NAC prevented this effect, maintaining follicle integrity similar to untreated animals. Ovaries of mice treated with PIP alone had similar percentage of normal follicles compared to control group. Additionally, the association of DOX and PIP preserved collagen levels similar to control, while PIP or NAC alone did not influence collagen distribution. Ovaries of mice treated with both DOX and NAC showed a reduction in stromal cells, but those treated with both DOX and PIP maintained the levels of collagens similar to control.

CONCLUSIONS: The DOX and PIP preserved the integrity of follicles and collagen fibers in mouse ovaries, which opens a new possibility to protect primordial follicles during chemotherapy.},
}

@article {pmid41424200,
year = {2025},
author = {Sadri, H and Shahrokhi, N and Ebrahimi-Rad, M and Mardani, M and Sadeghi, S and Pooya, M},
title = {Synergistic Antiba cterial and Antibiofilm Activity of N-acetylcysteine Combined with Niosomal Recombinant Lysostaphin against MRSA Staphylococcus aureus.},
journal = {Journal of drug targeting},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/1061186X.2025.2607397},
pmid = {41424200},
issn = {1029-2330},
abstract = {Wound infections significantly impair healing and often result in chronic wounds, burdening healthcare systems substantially. The principal pathogen in such infections is Staphylococcus aureus (S. aureus), which forms biofilms that resist host defenses and conventional therapies. To overcome these challenges, recombinant lysostaphin (rLyso) was encapsulated in niosomes using thin-film hydration and evaluated with N-acetylcysteine (NAC) against standard and clinical S. aureus strains. In this study, we assessed antibacterial and antibiofilm activities by determining the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC). The measurements were complemented using fluorescence and confocal microscopy. Cytotoxicity was assessed in L929 fibroblasts, and in vivo efficacy was histologically investigated in BALB/c mouse wound models. The NAC/niosomal rLyso formulation exhibited the most potent antibacterial and antibiofilm effects, significantly lowering the MIC values (standard: 1250/5.9 μg/ml; clinical: 1250/2 μg/ml) and achieving notable biofilm eradication (MBEC: standard: 5000/23.6 μg/ml; clinical: 1250/2 μg/ml).Cytotoxicity assays confirmed high biocompatibility, with nearly 100% cell viability at MIC, while NAC alone was highly toxic. The combination of two agents achieved full bacterial clearance in vivo and accelerated wound healing. As a result, these findings suggest that NAC combined with niosomal rLyso synergistically disrupts S. aureus biofilms, enhances antimicrobial activity, and promotes wound repair. Such features make it a promising therapeutic strategy against resistant staphylococcal infections.},
}

@article {pmid41422903,
year = {2025},
author = {Chaabani, H and Ayed, I and Rjiba, K and Abid, S and Eyer, J and Arnoult, D},
title = {Trifloxystrobin induces oxidative stress-dependent activation of the OMA1-DELE1-HRI integrated stress response leading to apoptosis in human neuroblastoma cells.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127562},
doi = {10.1016/j.envpol.2025.127562},
pmid = {41422903},
issn = {1873-6424},
abstract = {Trifloxystrobin (TFX), a potent inhibitor of complex III in the mitochondrial respiratory chain, is a widely used strobilurin fungicide whose neurotoxic mechanisms remain poorly defined. This study investigated the molecular pathways underlying TFX-induced toxicity in human SH-SY5Y neuronal-like neuroblastoma cells, with particular emphasis on oxidative stress, mitochondrial dysfunction, and activation of the Integrated Stress Response (ISR). TFX exposure (24 h) exhibited an IC50 of approximately 100 μM, induced G0/G1 cell cycle arrest, and triggered mitochondria-mediated apoptosis, as evidenced by loss of mitochondrial membrane potential (ΔΨm), Bax activation, cytochrome c release, DNA fragmentation, phosphatidylserine exposure, and caspase-3 activation. These effects were accompanied by increased mitochondrial superoxide levels and decreased ATP production, indicating profound mitochondrial impairment. Pretreatment with N-acetylcysteine (NAC) markedly restored cell viability, reduced ROS accumulation, prevented ΔΨm dissipation, and diminished apoptotic damage. Mechanistically, TFX activated the ISR through the OMA1-DELE1-HRI mitochondrial stress signaling axis, as confirmed by loss-of-function experiments targeting these proteins. Importantly, both NAC and the ISR inhibitor ISRIB (Integrated Stress Response InhiBitor) significantly attenuated ISR activation and the resulting apoptosis, demonstrating that oxidative stress serves as an upstream trigger for ISR engagement and cell death. Collectively, these findings reveal that TFX induces oxidative stress-dependent activation of the OMA1-DELE1-HRI ISR pathway, linking mitochondrial dysfunction to apoptosis in human neuroblastoma cells. To our knowledge, this is the first report identifying ISR activation as a mechanistic component of strobilurin fungicide-induced neurotoxicity.},
}

@article {pmid41422364,
year = {2025},
author = {Xing, HB and Li, HY and Zheng, GZ and Zhang, QH and Zhai, L and Wu, X and Du, SX and Li, XD},
title = {Resveratrol synergizes with cisplatin to suppress osteosarcoma U2-OS cells via up-regulating Cx43 and inducing ROS-dependent apoptosis.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {2218},
pmid = {41422364},
issn = {2730-6011},
support = {JCYJ20190812171411416//Science and Technology Research and Development Foundation of Shenzhen/ ; JCYJ20210324131405016//Science and Technology Research and Development Foundation of Shenzhen/ ; JCYJ20230807142814031//Science and Technology Research and Development Foundation of Shenzhen/ ; A2018523//Medical Science and Technology Research Foundation of Guangdong Province/ ; },
abstract = {BACKGROUND: Resveratrol (Res), a plant-derived polyphenol, exerts synergistic effects when combined with various chemotherapeutic drugs, enhancing the antitumor activity of traditional chemotherapy. However, whether Res combined with cisplatin (CDDP) produces a synergistic inhibitory effect on osteosarcoma cell growth and its underlying mechanisms remain unclear.

METHODS: We investigated the responses of U2-OS cells to Res, CDDP, or their combination using Cell Counting Kit-8 (CCK-8) for proliferation, flow cytometry for apoptosis, wound healing assays for migration, and Transwell assays for invasion. The effects of the two drugs on Wnt/β-catenin signaling were analyzed via quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, the relationship between Cx43 and Wnt/Wnt/β-catenin signaling was explored by knocking down Cx43 using lentiviral infection.

RESULTS: The combination of Res and CDDP exhibited greater cytotoxicity against osteosarcoma U2-OS cells than either drug alone, and this effect was synergistic as determined by the Chou-Talalay equation. Cx43 knockdown attenuated the strong antitumor effect of the Res + CDDP combination and restored Wnt/β-catenin signaling activity. Furthermore, the Res + CDDP combination generated more reactive oxygen species (ROS) than individual treatments, inducing ROS-dependent apoptosis, which was blocked by N-acetylcysteine (NAC).

CONCLUSIONS: Res combined with CDDP exerts a synergistic inhibitory effect on osteosarcoma by upregulating Cx43 and inducing ROS-dependent apoptosis. This study may provide a novel therapeutic strategy and potential clinical applications for osteosarcoma treatment.},
}

@article {pmid41421415,
year = {2025},
author = {Sun, R and Fan, H and Ma, Q and Li, X and Liu, J and Xu, C and Liu, C and Zhang, D and Ma, W},
title = {LL37-induced mitochondrial stress activates the mtDNA/cGAS/STING pathway to promote mast cell-mediated rosacea inflammation.},
journal = {Free radical biology & medicine},
volume = {244},
number = {},
pages = {422-434},
doi = {10.1016/j.freeradbiomed.2025.12.026},
pmid = {41421415},
issn = {1873-4596},
abstract = {BACKGROUND: Rosacea is a chronic inflammatory skin disease characterized by persistent facial erythema and telangiectasia. The antimicrobial peptide LL37 is a key initiator in rosacea, with mast cells serving as critical inflammatory mediators. However, the precise mechanism underlying LL37-induced mast cell degranulation remains unclear.

METHODS: The rosacea RNA-seq dataset GSE65914 was downloaded from the Gene Expression Omnibus (GEO) database and subjected to transcriptome analysis. DCFH-DA staining was performed to detect oxidative stress. Mitochondrial function was evaluated using MitoSOX and JC-1 staining. Calcein AM/Co[2+] quencher staining was employed to assess mitochondrial permeability transition pore (mPTP) opening. Transmission electron microscopy was utilized to observe mitochondrial ultrastructure. Cytosolic mitochondrial DNA (mtDNA) was evaluated via immunofluorescence and qPCR. Western blotting and CUT&RUN assays were conducted to detect activation of the cGAS/STING/NF-κB axis. Mast cell degranulation was assessed using ELISA. N-acetylcysteine (NAC) was administered to scavenge reactive oxygen species (ROS). Cyclosporin A (CsA) was used to inhibit mPTP opening. SP23 was applied for chemical degradation of STING. A LL37-induced rosacea-like dermatitis mouse model was established and topically treated with applied CsA/SP23 cream.

RESULTS: Transcriptomic profiling reveals significant enrichment of the cGAS/STING signaling pathway in rosacea lesions. LL37 induces oxidative stress-driven mitochondrial damage in mast cells, resulting in the leakage of mtDNA. Cytosolic mtDNA activates the cGAS/STING/NF-κB signaling pathway, inducing mast cell degranulation. ROS scavenging, blockade of mPTP or targeted degradation of STING significantly reduced mast cell activation. Animal experiments demonstrated that topical administration of CsA or SP23 suppressed cGAS/STING/NF-κB signaling in dermal mast cells and alleviated rosacea-like dermatitis.

CONCLUSION: LL37 promotes mast cell-driven inflammation through mitochondrial stress and innate immune activation and suggest that targeting the mtDNA/cGAS/STING pathway may offer a promising therapeutic strategy for rosacea.},
}

@article {pmid41419903,
year = {2025},
author = {Tekdemir, A and Ekici, MA and Çelikten, B and Helvacıoğlu Kıvanç, B},
title = {Comparison of calcium hydroxide removal efficiency of ethylenediaminetetraacetic acid, phytic acid and N-acetylcysteine using sonic activation: a micro-CT study.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-025-07455-4},
pmid = {41419903},
issn = {1472-6831},
abstract = {BACKGROUND: The aim of this study was to compare the efficacy of ethylenediaminetetraacetic acid (EDTA), phytic acid (IP6), and N-acetylcysteine (NAC) with sonic activation on the removal efficiency of calcium hydroxide (Ca(OH)2) from root canals with micro-computed tomography (micro-CT) analysis.

METHODS: Thirty-two extracted human mandibular first premolars were used in this study. The teeth were randomly divided into 4 groups based on the chelating agents to be used to remove Ca(OH)2 from the root canals (n=8). The root canals were prepared with the ProTaper rotary system up to X5. The specimens were scanned using micro-CT after preparation. Calcium hydroxide paste was delivered into root canals using a syringe system (SURE-Paste) combined with a lentulo spiral. All teeth were scanned using micro-CT to determine the filling volume. After 7 days, Ca(OH)2 was removed from the root canals. EDTA was used with syringe irrigation for the first group while, EDTA, IP6, and NAC were used with sonic activation at other groups, respectively, to remove Ca(OH)2. Teeth were scanned using micro-CT to calculate the volume and the percentage of Ca(OH)2 remnants. Data were analyzed statistically by one-way ANOVA and Duncan's tests (α=0.05).

RESULTS: None of the chelating agents and irrigation techniques completely removed Ca(OH)2. The percentage of the remnant volume of the Ca(OH)2 was significantly different between the groups (p < 0.05). The EDTA with syringe irrigation group had higher Ca(OH)2 remnant volume values compared to other groups (p < 0.05). The use of the EDTA, IP6, and NAC with sonic activation did not significantly affect the percentage of remaining Ca(OH)2 (p > 0.05).

CONCLUSIONS: The calcium hydroxide removal efficiencies of all three chelating agents were similar. IP6 and NAC can be used as alternatives to EDTA for Ca(OH)2 removal from the root canals with sonic activation.},
}

@article {pmid41418387,
year = {2025},
author = {Zhao, XY and Yan, M and Zheng, L and Gou, CL and Huang, Q and Li, LG and Yu, XR and Lu, JY and Hu, C and Zhang, SH and Kong, C and Leng, F and Li, TF},
title = {Curcumin-mediated photodynamic action disturbs TOM70-depedent MIC60 import to damage mitonchondria against breast cancer.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {274},
number = {},
pages = {113339},
doi = {10.1016/j.jphotobiol.2025.113339},
pmid = {41418387},
issn = {1873-2682},
abstract = {The regulation of mitochondrial membrane proteins is of crucial significance for breast cancer therapy. TOM70, which located in mitochondria outer membrane, could import MIC family molecules to preserve mitochondrial homeostasis. However, there are few agents targeting TOM70. Therein, the effects of curcumin and it's mediated photodynamic therapy (PDT) on the TOM70 and mitochondrial function for breast cancer treatment were investigated. The 4 T1 and MDA-MB-231 cells were utilized as the breast cancer cells. The 4 T1 cell-bearing mice were constructed as the breast cancer animal model. The anti-cancer efficacy was validated using the CCK-8, Annexin-V/PI staining, colony formation. The associated molecules were detected by Western blots (WB), RT-qPCR, and Immunohistochemistry (IHC). The target was verified by molecular docking, CETSA, and DARTS. The mitochondrial proteins and DNA were extracted for the MIC60 and mtDNA damage detection. Curcumin treatment showed poor efficacy in the breast cancer model, as characterized by cell viability, apoptosis, proliferation of breast cancer cells, and the growth of tumor grafts in mice. However, curcumin-mediated PDT inhibited breast cancer in vitro and in vivo. Further exploration identified curcumin bond to TOM70, which is highly expressed in breast cancer, thereby activating it. But curcumin-induced PDT inactivated TOM70 through generated reactive oxygen species (ROS), which in turn interfered with the binding of MIC60 and its translocation into mitochondria. Curcumin-triggered PDT led to severe mitochondrial damage compared with the curcumin treatment, which could be blocked by the N-Acetylcysteine (NAC). Additional TOM70 rescue dampened curcumin PDT-mediated mitochondrial damage and anti-breast cancer efficacy. To summarize, the present research identifies curcumin-induced PDT inactivated TOM70, thereby attenuating MIC60 import, leading to mitochondrial damage against breast cancer. We propose a novel approach to tumor treatment through the regulation of mitochondrial membrane proteins using the phytomedicine-driven PDT.},
}

@article {pmid41415424,
year = {2025},
author = {Rukh, S and Meechan, DW and Roberts, A and Siggins, C and Erwin, ZD and Maynard, TM and LaMantia, AS},
title = {Distinct cellular and transcriptional mechanisms mediate an antioxidant therapeutic response in 22q11-deleted upper layer cortical projection neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41415424},
issn = {2692-8205},
abstract = {We characterized cellular and molecular mechanisms underlying the therapeutic response in vitro and in vivo to the antioxidant N-acetyl cysteine (NAC), which in the LgDel 22q11.2 Deletion Syndrome mouse model restores growth and connectivity of upper layer cortical projection neurons (Layer 2/3 PNs) and improves cognitive performance. NAC treatment of primary cultured LgDel L 2/3 PNs does not restore these neurons to a wild type (WT) state. Rather than returning to the bimodal dendrite and axon size distribution seen in WT, LgDel L 2/3 PN dendrite and axon growth in vitro increases unimodally in response to NAC. In parallel, altered expression of 22q11-deleted genes and presumed downstream targets are unchanged. Instead, novel antioxidant defense and neuronal growth genes are differentially expressed: some generally NAC-regulated, others responsive only in the context of 22q11 deletion. Apparently, NAC ameliorates L 2/3 PN developmental pathology without restoring WT cell states or typical expression of mutant genes or their downstream targets. NAC also elicits differential expression of antioxidant defense genes in 22q11-deleted L 2/3 PNs-but not L 5/6 counterparts-in the developing postnatal LgDel mouse cortex, rather than modulating 22q11 genes or downstream targets. These NAC-dependent, L 2/3 PN-selective in vivo cellular and transcriptional changes differ substantially from those in primary culture. Thus, despite some in vitro and in vivo parallels, the NAC therapeutic response that diminishes oxidative stress-related L 2/3 PN circuit and behavioral pathology due to 22q11 deletion has a unique in vivo signature.},
}

@article {pmid41415037,
year = {2025},
author = {Qi, J and Yin, Z and Peng, Y and Zhang, F and Li, Y and Xia, X and Jia, X},
title = {Evaluation of antioxidant co-therapy for polymyxin B-associated nephrotoxicity and mortality: a real-World retrospective cohort study.},
journal = {Journal of pharmaceutical policy and practice},
volume = {18},
number = {1},
pages = {2568673},
pmid = {41415037},
issn = {2052-3211},
abstract = {BACKGROUND: Polymyxin B is increasingly used to treat infections caused by multidrug-resistant gram-negative bacteria; however, its widespread clinical use is hindered by the high incidence of nephrotoxicity. Antioxidants, such as vitamin C, N-acetylcysteine (NAC), and methionine, have demonstrated renoprotective effects in preclinical models, although clinical evidence remains limited. This study aimed to investigate the potential protective effects of these antioxidants against polymyxin B-associated acute kidney injury (AKI) in real-world clinical practice.

METHODS: This retrospective cohort study included adult in patients who received intravenous polymyxin B for ≥ 3 days between August 2018 and August 2020. The patients were classified into an antioxidant group (co-administered vitamin C, NAC, or methionine for ≥ 3 days) or a control group. Propensity score weighting was applied to balance the baseline covariates. The primary outcome was the incidence of polymyxin B-associated AKI and the secondary outcome was discharge mortality.

RESULTS: A total of 321 patients were included, with 77 and 244 patients in the antioxidant and control groups, respectively. After propensity score adjustment, there were no statistically significant differences in AKI incidence (26.9% vs. 19.2%, P = 0.352) or discharge mortality (7.7% vs. 15.4%, P = 0.220) between the groups. Subgroup analyses of individual antioxidants also showed no significant differences in AKI or mortality, except for a lower unadjusted mortality in the methionine group (0% vs. 13.9%, P = 0.042), which lost significance after adjustment.

CONCLUSION: This exploratory study did not provide conclusive evidence that vitamin C, NAC, or methionine reduced the risk of polymyxin B-associated AKI. The potential association between antioxidant use and reduced mortality warrants further investigation. Large-scale prospective studies are required to confirm the clinical utility of antioxidant cotherapy in patients receiving polymyxin B.},
}

@article {pmid41412528,
year = {2025},
author = {Wu, Z and Kuang, Z and Liang, L and Liu, J and Wang, G and Zou, F},
title = {TGF-β/LAMB3 axis drives ROS-dependent renal fibrosis under hypoxic conditions.},
journal = {Free radical biology & medicine},
volume = {244},
number = {},
pages = {395-409},
doi = {10.1016/j.freeradbiomed.2025.12.024},
pmid = {41412528},
issn = {1873-4596},
abstract = {Hypoxia is a well-established driver of renal fibrosis, but the underlying mechanisms remain unclear. In this study, we demonstrate that hypoxia-induced excessive reactive oxygen species (ROS) drive renal fibrosis, while the antioxidant N-acetylcysteine (NAC) ameliorates this pathological process. Hypoxia-induced ROS overproduction in renal tubular epithelial cells acts as the central regulator driving concurrent partial epithelial-mesenchymal transition (pEMT) and TGF-β secretion. Integrated ATAC-seq and RNA-seq analysis demonstrates that TGF-β treatment induces LAMB3 upregulation in fibroblasts through enhanced chromatin accessibility at its promoter region. Mouse model of hypoxic renal fibrosis shows marked upregulation of both TGF-β and LAMB3, implicating their involvement in fibrogenesis under hypoxic conditions. Kidney-targeted knockdown of LAMB3 significantly ameliorates hypoxia-induced renal fibrosis. TGF-β secreted by hypoxic renal tubular epithelial cells activates canonical Smad signaling in fibroblasts, which in turn upregulates LAMB3 to initiate PI3K/AKT-dependent myofibroblast differentiation. Pharmacological ROS scavenging by NAC potently disrupts this TGF-β/LAMB3 axis, improving kidney fibrosis under hypoxic conditions. Our findings reveal that TGF-β/LAMB3 axis drives ROS-dependent renal fibrosis under hypoxic conditions, identifying LAMB3 and ROS as potential therapeutic targets for fibrotic kidney diseases.},
}

@article {pmid41412471,
year = {2025},
author = {Chang, YC and Lin, WH and Ko, HH and Lo, YC and Chang, HS and Lin, HC and Chen, YF},
title = {Formononetin protects against oxaliplatin-induced peripheral neurotoxicity via Nrf2/HO-1 antioxidant pathway without impairing anticancer efficacy.},
journal = {Neurotoxicology},
volume = {112},
number = {},
pages = {103368},
doi = {10.1016/j.neuro.2025.103368},
pmid = {41412471},
issn = {1872-9711},
abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) is a common and intolerable adverse effect of oxaliplatin and paclitaxel. The intolerance to CIPN symptoms often leads to poor compliance and treatment discontinuation, jeopardizing survival outcomes. However, no Food and Drug Administration (FDA)-approved interventions exist for preventing or treating CIPN. A major challenge has been that neuroprotective candidates often diminish the effectiveness of chemotherapy, limiting their translational development. Here, we aimed to identify neuroprotective agents that maintain anticancer activity. Using ND7/23 dorsal root ganglion neurons treated with oxaliplatin and paclitaxel, we screened our compound library and identified formononetin, a natural isoflavone, as a promising candidate. Formononetin significantly protected ND7/23 DRG neurons against oxaliplatin-induced neurotoxicity by reducing oxidative stress and apoptosis via activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway and modulating protein expressions of pro-apoptotic B-cell lymphoma 2-associated X (Bax) and anti-apoptotic B-cell lymphoma 2 (BCL-2). Formononetin showed limited protection against paclitaxel-induced structural neurite damage. Importantly, unlike the ROS scavenger N-acetylcysteine (NAC), which decreased the anticancer effectiveness of both oxaliplatin and paclitaxel, formononetin maintained their anticancer effects in colorectal cancer HT29 cells and cervical cancer SiHa cells. Taken together, formononetin holds potential as a neuroprotectant to prevent oxaliplatin-induced neurotoxicity without compromising anticancer efficacy.},
}

@article {pmid41401723,
year = {2025},
author = {Lin, CH and Lane, HY},
title = {Sodium benzoate treatment linked to increased glutathione levels and improved positive and negative symptoms, global function, and quality of life in patients with clozapine-resistant schizophrenia: secondary analysis of a randomized clinical trial.},
journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology},
volume = {103},
number = {},
pages = {112733},
doi = {10.1016/j.euroneuro.2025.11.010},
pmid = {41401723},
issn = {1873-7862},
abstract = {Oxidative stress is implicated in schizophrenia. Glutathione (GSH), a crucial endogenous antioxidant, is usually reduced in individuals with schizophrenia. GSH and its precursor, N-acetyl cysteine, have demonstrated potential as adjunctive treatment for schizophrenia; however, their effectiveness appears inconsistent, possibly because of their limited ability to penetrate the blood-brain barrier (BBB). Administration of sodium benzoate, capable of crossing BBB, enhanced GSH capacity and antipsychotic-like activity in animals. Further, adjunctive benzoate therapy improved clinical and functional outcomes in patients with schizophrenia, including clozapine-resistant schizophrenia (CRS). Whether sodium benzoate can also boost GSH to exert its therapeutic efficacy for schizophrenia deserves elucidation. This secondary analysis used data from a double-blind trial, in which 60 patients with CRS were randomized to receive addon treatment of sodium benzoate (n = 40) or placebo (n = 20) for 6 weeks. Clinical and functional assessments were conducted bi-weekly. Plasma levels of GSH were assayed at baseline and endpoint. As a result, six-week treatment of sodium benzoate was linked to increased GSH levels than placebo. Among the 40 benzoate receivers, the changes in GSH levels were correlated with the improvements in positive symptoms, negative symptoms, quality of life, and global function. In comparison, among placebo recipients, GSH changes were not associated with any changes in clinical or functional variables. The findings suggest that benzoate treatment may be related with elevation in GSH levels in CRS patients and improvement in functional outcomes as well as positive and negative symptoms. Longer-term studies in other populations are necessary in the future.},
}

@article {pmid41399893,
year = {2025},
author = {Aly, S and Ali, M and Sayed, A and Hamadneh, BN and Yousef, M and Khalil, M and Rizk, A and El-Messery, TM and Kamel, RM and Mohammed, BM and Abdelkarim, DO and Younis, M},
title = {Enhanced color and antioxidant properties of sunflower protein concentrates extracted under alkaline conditions using anti-greening reagents.},
journal = {Journal of the science of food and agriculture},
volume = {},
number = {},
pages = {},
doi = {10.1002/jsfa.70389},
pmid = {41399893},
issn = {1097-0010},
abstract = {BACKGROUND: Sunflower protein concentrates (SPCs) are valuable plant-derived ingredients. However, their application is limited by greening during alkaline extraction, caused by chlorogenic acid (CGA) oxidation. This study systematically developed and characterized SPCs extracted under alkaline conditions with two anti-greening reagents, N-acetylcysteine (NAC) and ascorbic acid (ASC), each applied at 12 mg g[-1] meal. The findings provide novel insights into how these reagents modulate the amino acid composition, structural conformation, and antioxidant potential, and improve color in SPCs obtained from completely hulled (SPC-CH) and unhulled (SPC-UH) sunflower seeds.

RESULTS: The addition of ASC during extraction increased the total phenolic content to 130.51 g kg[-1] CGA in SPC-CH and 119.08 g kg[-1] CGA in SPC-UH. The antioxidant capacity, measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reached 1084.38 mmol kg[-1] Trolox equivalent (TE) in ASC-treated SPC-CH, compared with 891.08 and 937.58 mmol kg[-1] TE in the distilled water (DW) and NAC treatments. Both ASC and NAC inhibited greening, producing SPCs with a more acceptable yellowish color. Structural analysis showed only minor alterations in protein secondary structure across all extraction methods, indicating that protein integrity was maintained. Thermal stability and amino acid composition evaluations further supported the suitability of these SPCs for food applications.

CONCLUSION: The use of ASC and NAC as anti-greening reagents improved the color and antioxidant potential of sunflower protein concentrates while maintaining structural stability. This approach enables the sustainable production of high-quality SPCs, suitable for functional food formulations. © 2025 Society of Chemical Industry.},
}

@article {pmid41389180,
year = {2025},
author = {Naik, S and Boopathy, R and Das, T and Mishra, M},
title = {Unravelling the Mechanism of N-Acetylcysteine in Alleviating Smoke-Induced Hypoxia-Driven Ocular Defects in Drosophila melanogaster.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {291},
pmid = {41389180},
issn = {1559-1182},
mesh = {Animals ; *Drosophila melanogaster/drug effects ; *Acetylcysteine/pharmacology/therapeutic use ; *Hypoxia/complications/drug therapy ; *Smoke/adverse effects ; *Eye/drug effects/pathology ; Drosophila Proteins/metabolism/genetics ; Particulate Matter ; },
abstract = {Smoke that includes particulate matter (PM), carbon monoxide (CO), sulfur dioxide (SO2), and nitrogen dioxide (NO2) has a substantial negative impact on human health. PM, which can vary from tiny dust to coarse particles, enters the respiratory system and reduces the amount of oxygen taken in by the lungs, leading to hypoxia. Drosophila was employed as the model organism to study the effects of smoke-induced hypoxia on eye development and to evaluate N-Acetylcysteine (NAC) as a potential protective agent. In this study, Drosophila eggs were exposed to 0.1 g of coconut husk smoke . Furthermore, different size fractions of particulate matter (PM) (10, 2.5, and 1.0 µm) and concentrations of different gases were monitored to correlate the inference of PM and gases on the tracheal terminal tube. To determine whether CO and PM (10, 2.5, and 1 µm) contribute to hypoxia, quantitative PCR analysis of sima and tango was performed, revealing a significant upregulation of sima expression. Impairment of the tracheal terminal branches results in reduced oxygen delivery to tissues, which affects the development of photoreceptor cells. Biochemical estimation disclosed the presence of reactive oxygen species, which led to cellular injury and DNA damage. The marked downregulation of NinaE (Rh1), Rh3, and Rh6 causes internal defect in the eye. Treatment with NAC restored all these abnormalities to normal levels. This research provides insight into how smoke-induced hypoxia disrupts eye development, while NAC shows potential as an effective therapeutic agent in counteracting its harmful effects.},
}

Animals
*Drosophila melanogaster/drug effects
*Acetylcysteine/pharmacology/therapeutic use
*Hypoxia/complications/drug therapy
*Smoke/adverse effects
*Eye/drug effects/pathology
Drosophila Proteins/metabolism/genetics
Particulate Matter

@article {pmid41385627,
year = {2025},
author = {Li, Y and Yu, T and Wang, Z and Wang, J and Tang, Y and Zhang, Y and Li, H and Zhou, H and Yin, P and Yao, S},
title = {A fluorescent probe for concurrent detection of cysteine, homocysteine, and superoxide anion.},
journal = {Science advances},
volume = {11},
number = {50},
pages = {eadx6659},
pmid = {41385627},
issn = {2375-2548},
mesh = {*Cysteine/analysis/metabolism ; *Superoxides/analysis/metabolism ; *Homocysteine/analysis/metabolism ; Animals ; *Fluorescent Dyes/chemistry ; Zebrafish ; Humans ; Oxidation-Reduction ; Oxidative Stress ; Mice ; },
abstract = {Redox imbalance is a key factor in the pathogenesis of diseases such as epilepsy and liver injury. Superoxide anion (O2[•-]), cysteine (Cys), and homocysteine (Hcy) play central roles in maintaining redox homeostasis, and their dysregulation drives oxidative stress and disease progression. Here, we report a multifunctional fluorescent probe, BPC, capable of simultaneously and selectively detecting Cys, Hcy, and O2[•-] in complex biological environments. BPC shows high sensitivity, selectivity, and biocompatibility, enabling real-time visualization of redox fluctuations in living cells and zebrafish with minimal cytotoxicity. In pentylenetetrazole (PTZ)- and acetaminophen (APAP)-induced models of epilepsy and liver injury, BPC revealed notable alterations in Cys, Hcy, and O2[•-] levels, providing mechanistic insights into redox dysregulation. Moreover, BPC successfully tracked redox restoration following N-acetylcysteine (NAC) treatment. These findings establish BPC as a versatile tool for redox biology and highlight its promise for diagnostic and therapeutic applications.},
}

*Cysteine/analysis/metabolism
*Superoxides/analysis/metabolism
*Homocysteine/analysis/metabolism
Animals
*Fluorescent Dyes/chemistry
Zebrafish
Humans
Oxidation-Reduction
Oxidative Stress
Mice

@article {pmid41383104,
year = {2025},
author = {Kim, HB and Kim, YJ and Lim, HM and Suh, SW and Lee, JH and Lee, CJ and Woo, RS},
title = {N-acetylcysteine Restores Impaired Dentate Gyrus Neurogenesis in a Neonatal Maternal Separation Rat Model.},
journal = {Experimental neurobiology},
volume = {34},
number = {6},
pages = {277-288},
pmid = {41383104},
issn = {1226-2560},
abstract = {Early-life stress (ELS) is a major contributor to neurodevelopmental vulnerability, particularly within the dentate gyrus (DG), where oxidative burden and microglial activation disrupt adult neurogenesis. Here, we examined whether N-acetylcysteine (NAC), a cysteine prodrug and glutathione precursor, could counteract impaired neurogenesis induced by neonatal maternal separation (NMS). Adolescent NAC administration restored the number of Ki67[+] proliferating progenitors and DCX[+] immature neurons in the DG of NMS rats, accompanied by reduced reactive oxygen species, suppressed iNOS induction, and attenuated microglial activation. NAC also normalized EAAC1 expression, indicating enhanced neuronal antioxidant capacity. Notably, NAC rescued diminished neurogenesis in EAAC1 knockout mice, demonstrating its efficacy under both stress-induced and transporter-deficient redox imbalance. These findings identify NAC as a potent modulator of hippocampal neuroplasticity, acting through the restoration of redox and inflammatory homeostasis, and support its potential as an early therapeutic strategy to mitigate long-lasting neurodevelopmental consequences of ELS.},
}

@article {pmid41381010,
year = {2025},
author = {Xu, R and Liang, XW and Cai, QH and Cai, YW and Sun, N and Li, YP and Shi, ZJ and Hu, B and He, XH and Zha, QB and Ouyang, DY},
title = {Hyperthermia induces reductive stress in murine macrophages.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1872},
number = {3},
pages = {168133},
doi = {10.1016/j.bbadis.2025.168133},
pmid = {41381010},
issn = {1879-260X},
abstract = {Hyperthermia induces heat stress (HS) and injuries in various human organs, or even leads to mortality, yet the underlying mechanism is incompletely uncovered. Our study revealed that HS in macrophages induced concurrent activation of pyroptotic, apoptotic, and necroptotic pathways, and the formation of PANoptosome-like complexes. However, these processes proceeded independently of ROS, as the ROS scavengers N-acetyl cysteine and mito-TEMPO failed to prevent the cell death (PANoptosis) despite effectively suppressing oxidative stress. Instead, HS caused reductive stress marked by NADPH accumulation and thioredoxin (Trx) system dysfunction. Trx1 aggregation impaired redox regulation, leading to aberrant disulfide bonding in mitochondrial proteins (e.g., Drp1, Bcl-2). The Trx reductase exogenous substrate DTNB partially rescued cell viability by restoring redox balance, confirming Trx failure as a key driver of cytotoxicity. Notably, such reductive stress was accompanied by DNA damage and mitochondrial injury during HS. Pharmacologic intervention revealed that pan-caspase inhibition by IDN-6556 abrogated the reductive stress and its consequences (ROS production, DNA damage, and mitochondrial injury), and suppressed the pyroptotic/apoptotic signaling and lytic cell death. However, the caspase inhibition alone triggered compensatory receptor-interaction protein 3 (RIPK3) activation, necessitating dual inhibition with GSK'872 (RIPK3 inhibitor) to fully block PANoptotic cell death. In vivo validation showed protection of the IDN-6556/GSK'872 combination against HS-induced injury on the intestines through reduced DNA damage and PANoptosis suppression. Our study reveals that reductive stress-mediated Trx dysfunction, not oxidative stress, underlies HS-induced PANoptosis. Dual targeting of caspases and RIPK3 provides a novel therapeutic avenue against heat shock-associated diseases.},
}

@article {pmid41380831,
year = {2026},
author = {Etemadi, Y and Akakpo, JY and Fields, TA and Ramachandran, A and Jaeschke, H},
title = {Differential effects on acetaminophen-induced nephrotoxicity and liver injury following modulation of glutathione resynthesis.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {208},
number = {},
pages = {115896},
doi = {10.1016/j.fct.2025.115896},
pmid = {41380831},
issn = {1873-6351},
mesh = {Animals ; *Acetaminophen/toxicity ; Male ; *Glutathione/biosynthesis/metabolism ; Mice, Inbred C57BL ; *Chemical and Drug Induced Liver Injury/metabolism ; *Acute Kidney Injury/chemically induced/metabolism ; Mice ; *Kidney/drug effects/metabolism/pathology ; Liver/drug effects/metabolism ; Alanine Transaminase/blood/metabolism ; Acetylcysteine/pharmacology ; Buthionine Sulfoximine/pharmacology ; Blood Urea Nitrogen ; Hepatitis A Virus Cellular Receptor 1/metabolism ; },
abstract = {Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF), with acute kidney injury (AKI) increasing morbidity and mortality. N-acetylcysteine (NAC) prevents APAP-induced liver damage, but not AKI, highlighting the need to address differential inter-organ responses to APAP toxicity. We investigated the relationship between hepatic glutathione (GSH) depletion, liver injury, and subsequent kidney damage following APAP overdose. Male C57BL/6J mice received either moderate (300 mg/kg) or severe (600 mg/kg) overdoses of APAP, with or without buthionine sulfoximine (BSO, 50 mg/kg) to deplete GSH, or NAC (500 mg/kg) to replenish GSH. A moderate APAP overdose elevated liver injury markers (alanine aminotransferase, ALT) without significantly affecting blood urea nitrogen (BUN) levels, though kidney injury molecule-1 (KIM-1) expression increased. A severe overdose significantly increased ALT activities, and BUN and creatine levels, together with marked upregulation of renal KIM-1 and histological evidence of cortical damage. BSO exacerbated APAP-induced kidney but not liver injury, where GSH remained depleted at 24 h. In contrast, NAC protected against APAP hepatotoxicity but not AKI. Thus, these findings demonstrate critical organ-specific responses to APAP toxicity and underscore the need for targeted therapeutic strategies specifically addressing APAP-induced kidney injury.},
}

Animals
*Acetaminophen/toxicity
Male
*Glutathione/biosynthesis/metabolism
Mice, Inbred C57BL
*Chemical and Drug Induced Liver Injury/metabolism
*Acute Kidney Injury/chemically induced/metabolism
Mice
*Kidney/drug effects/metabolism/pathology
Liver/drug effects/metabolism
Alanine Transaminase/blood/metabolism
Acetylcysteine/pharmacology
Buthionine Sulfoximine/pharmacology
Blood Urea Nitrogen
Hepatitis A Virus Cellular Receptor 1/metabolism

@article {pmid41378547,
year = {2024},
author = {Kotze, C and Swanepoel, J and Kruger, EC and Decloedt, E},
title = {The management and clinical outcome of paracetamol poisoning in South African adults: A single-centre retrospective review.},
journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde},
volume = {114},
number = {12},
pages = {e1986},
doi = {10.7196/SAMJ.2024.v114i12.1986},
pmid = {41378547},
issn = {2078-5135},
mesh = {Humans ; *Acetaminophen/poisoning ; Female ; Retrospective Studies ; South Africa/epidemiology ; Adult ; Male ; *Chemical and Drug Induced Liver Injury/mortality/etiology/therapy/epidemiology ; *Drug Overdose/mortality ; *Analgesics, Non-Narcotic/poisoning ; Young Adult ; Acetylcysteine/therapeutic use ; Antidotes/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Paracetamol is a commonly prescribed drug, and often implicated in pharmaceutical overdoses. Paracetamol-induced hepatotoxicity is a common cause of acute liver failure in many high-income countries, but little is known about the factors associated with severity of liver injury and poor clinical outcomes among those treated in sub-Saharan African settings.

OBJECTIVE: To describe the characteristics of patients presenting with paracetamol poisoning, and to identify factors associated with severity of liver injury and poor outcomes in adults with biochemical evidence of paracetamol-induced liver damage treated at a South African (SA) tertiary hospital.

METHODS: A retrospective medical record review was conducted of all adult patients (≥18 years old) admitted between August 2013 and August 2018 to a tertiary referral centre in Cape Town, SA, with paracetamol poisoning and biochemical evidence of liver impairment. Demographics, clinical and laboratory data were obtained. Management practices and clinical outcomes were assessed.

RESULTS: The records of 91 patients were included in the analysis. The median (interquartile range (IQR)) age was 29 (23 - 39) years, and 63% were female. The majority of paracetamol poisonings followed an intentional overdose (91%). Acute single ingestions were the most common (81%) type of toxic ingestion, compared with staggered overdose and repeated supratherapeutic ingestion, and the median (IQR) number of tablets ingested was 22 (20 - 39). Two-thirds of patients developed mild liver injury and 12% developed acute kidney injury. The overall mortality rate was 12%. Mortality was lower in those who received intravenous N-acetylcysteine (NAC) before serum paracetamol concentrations were known compared with those who only received NAC after concentrations were known (8.8% v. 36%, p=0.03). A significant proportion of deaths occurred in those with accidental overdose compared with those with intentional overdosing (57% v. 7.2%; p=0.004). People living with HIV (p=0.04), a history of chronic alcoholism (p=0.04), chronic liver disease (p=0.01) and severity of acute kidney stage (p<0.001) were all associated with increased mortality.

CONCLUSION: A high case fatality rate was observed in the studied population. Early identification of at-risk individuals and prompt initiation of NAC can reduce poor outcomes. Larger multicentre studies are needed to identify independent predictors of paracetamol-induced hepatoxicity and mortality in Africa.},
}

Humans
*Acetaminophen/poisoning
Female
Retrospective Studies
South Africa/epidemiology
Adult
Male
*Chemical and Drug Induced Liver Injury/mortality/etiology/therapy/epidemiology
*Drug Overdose/mortality
*Analgesics, Non-Narcotic/poisoning
Young Adult
Acetylcysteine/therapeutic use
Antidotes/therapeutic use
Treatment Outcome

@article {pmid41377542,
year = {2025},
author = {Thoppil, J and Farrar, JD and Sharma, D and Kirby, S and Mobley, A and Courtney, DM},
title = {Reactive oxygen species elevations in human immune cell subsets during sepsis are mitigated by norepinephrine and N-acetylcysteine.},
journal = {World journal of critical care medicine},
volume = {14},
number = {4},
pages = {108638},
pmid = {41377542},
issn = {2220-3141},
abstract = {BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Peripheral blood mononuclear cells (PBMCs) are critical mediators of the immune response and may exhibit redox imbalance during sepsis. Reactive oxygen species (ROS) are known to influence immune cell signaling, and excessive ROS accumulation may contribute to sepsis-associated immune alterations.

AIM: To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine (NE) or N-acetylcysteine (NAC) modulate ROS levels following inflammatory stimulation in vitro.

METHODS: PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection. Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry. PBMCs were also stimulated in vitro with lipopolysaccharide (LPS) or hydrogen peroxide (H2O2), with or without co-treatment with NE or NAC.

RESULTS: ROS levels were significantly elevated in CD3+ and CD14+ cells from septic patients compared to controls. In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+ and CD14+ cells, which was attenuated by co-treatment with NE or NAC.

CONCLUSION: ROS levels are elevated in specific PBMC subsets in sepsis, particularly CD3+ T cells and CD14+ monocytes. NE and NAC reduced ROS accumulation in vitro, supporting their potential role as redox modulators. These findings warrant further mechanistic investigation into immune redox regulation in sepsis.},
}

@article {pmid41373660,
year = {2025},
author = {Izquierdo-Bermejo, S and Chioua, M and Hadjipavlou-Litina, D and López-Muñoz, F and Marco-Contelles, J and Oset-Gasque, MJ},
title = {Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373660},
issn = {1422-0067},
support = {UCJC-NENs, UCJC-CHONICEN,UCJC- HDACi-ICTUS//Universidad Camilo José Cela (UCJC)/ ; SAF2015-65586-R//Spanish Ministry of Economy and Competitiveness/ ; },
mesh = {*Oximes/pharmacology/chemistry ; *Neuroprotective Agents/pharmacology/chemistry/chemical synthesis ; *Nitrogen Oxides/pharmacology/chemistry ; *Antioxidants/pharmacology/chemistry/chemical synthesis ; *Brain Ischemia/drug therapy/metabolism/pathology ; Animals ; *Steroids/chemistry/pharmacology ; Cell Survival/drug effects ; Humans ; Rats ; },
abstract = {Despite the substantial global impact of ischemic stroke, current therapeutic options remain limited and only partially effective. To advance neuroprotective strategies that could improve the safety and efficacy of existing treatments while preserving brain tissue, we synthesized and evaluated seven new nitrones (MC3, MC5, MC7) and oximes (MC1, MC2, MC4, MC6) derived from different neuroactive steroids-ethisterone (MC1-3), mifepristone (MC4-5) and stanolone (MC6-7)-in an in vitro model of cerebral ischemia. Overall, these derivatives exhibited neuroprotective and antioxidant effects superior to those of the reference compounds cholesteronitrone ChN2, α-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC). Notably, nitrones showed greater neuroprotective, anti-necrotic, and antioxidant potency than their corresponding oximes, regardless of the degree of molecular conjugation. Among them, the stanolone-derived nitrone MC7, which lacks conjugated double bonds, displayed the most balanced and robust profile, consistently enhancing cell viability, reducing necrotic cell death, and suppressing superoxide anion production. Consequently, MC7 has been selected as a promising lead compound for further in vivo studies of cerebral ischemia.},
}

*Oximes/pharmacology/chemistry
*Neuroprotective Agents/pharmacology/chemistry/chemical synthesis
*Nitrogen Oxides/pharmacology/chemistry
*Antioxidants/pharmacology/chemistry/chemical synthesis
*Brain Ischemia/drug therapy/metabolism/pathology
Animals
*Steroids/chemistry/pharmacology
Cell Survival/drug effects
Humans
Rats

@article {pmid41373526,
year = {2025},
author = {Pachhapure, S and Shin, YM and Kim, DG and Choi, DR and Yun, JI and Kim, JH and Jang, BC},
title = {The Mitigating Effect and Mechanism of Polydeoxyribonucleotide Against Zoledronic Acid-Induced Growth Suppression of Human Gingival Fibroblasts.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373526},
issn = {1422-0067},
support = {B20220018//This work was supported by a grant (No. B20220018) from Zerone Cellvane Inc./ ; },
mesh = {Humans ; *Zoledronic Acid/pharmacology/adverse effects ; *Gingiva/cytology/drug effects/metabolism ; *Polydeoxyribonucleotides/pharmacology ; *Fibroblasts/drug effects/metabolism/cytology ; Cell Proliferation/drug effects ; STAT3 Transcription Factor/metabolism ; Reactive Oxygen Species/metabolism ; Cell Line ; Phosphorylation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; },
abstract = {Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. However, its clinical application is limited by adverse effects, notably bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is associated with cytotoxicity in oral mucosal cells. Polydeoxyribonucleotide (PDRN), a salmon sperm-derived DNA polymer with regenerative and anti-inflammatory properties, has shown therapeutic potential in tissue repair; however, its ability to mitigate ZA-induced cytotoxicity remains poorly understood. Here, we investigated the molecular mechanisms of ZA-induced toxicity in HGF-1 cells, a human gingival fibroblast line, and evaluated the protective effects of PDRN. ZA treatment (50 µM, 48 h) significantly inhibited HGF-1 cell growth, accompanied by reduced phosphorylation of protein kinase B (PKB) and signal transducer and activator of transcription 3 (STAT-3), along with increased phosphorylation of TANK-binding kinase 1 (TBK1). TBK1 silencing restored cell growth under ZA exposure, whereas silencing PKB or STAT-3 further suppressed cell growth even without ZA. Co-treatment with PDRN (100 µg/mL) effectively prevented and reversed ZA-induced HGF-1 cytotoxicity. Mechanistically, PDRN inhibited ZA-induced TBK1 phosphorylation and partially restored PKB phosphorylation, though it did not reverse the reduction in p-STAT-3. Additionally, ZA significantly elevated intracellular reactive oxygen species (ROS) levels at 8 h, which were attenuated by PDRN. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress.},
}

Humans
*Zoledronic Acid/pharmacology/adverse effects
*Gingiva/cytology/drug effects/metabolism
*Polydeoxyribonucleotides/pharmacology
*Fibroblasts/drug effects/metabolism/cytology
Cell Proliferation/drug effects
STAT3 Transcription Factor/metabolism
Reactive Oxygen Species/metabolism
Cell Line
Phosphorylation/drug effects
Protein Serine-Threonine Kinases/metabolism

@article {pmid41371424,
year = {2025},
author = {Liu, W and Liu, Y and Shi, J and Li, J and Li, G and Quan, J and Zhao, W},
title = {Prepuberty exposure to polystyrene nanoplastics induces cardiac inflammation through calcium overload-mediated ROS/JAK1/STAT3 signaling cascade.},
journal = {Free radical biology & medicine},
volume = {244},
number = {},
pages = {133-146},
doi = {10.1016/j.freeradbiomed.2025.12.006},
pmid = {41371424},
issn = {1873-4596},
abstract = {Polystyrene nanoparticles (PS-NPs) pose a significant threat to human health. In the present study, we aimed to investigate the toxicological effects of low-dose of PS-NPs on cardiac development and function following prepubertal exposure. Postpartum dams and their offspring were exposed to PS-NPs at concentrations of 0, 50 mg/L, and 100 mg/L via their daily drinking water, commencing from gestational day 1 and continuing until postnatal day (PND) 35. The results demonstrated that PS-NPs induced cardiac developmental toxicity in offspring. Proteomic analysis indicated that PS-NP exposure led to differentially expressed proteins, which were mainly enriched in JAK/STAT3 signaling pathway, inflammatory response pathway and antioxidant response signaling pathway. We subsequently found that exposure to PS-NPs in HL-1 cells increased the levels of reactive oxygen species (ROS), IL-6, IL-17, and TNF-α, as well as upregulated the expression of pJAK1 and pSTAT3. Treatment of HL-1 cells with N-Acetylcysteine (NAC) normalized the activity of the JAK1/STAT3 pathway and the levels of inflammatory cytokines. Furthermore, either inhibition of JAK1 with upadacitinib or knockdown of STAT3 in PS-NP-exposed HL-1 cells led to proinflammatory cytokine levels comparable to those in control cells. Given the well-established link between oxidative stress and mitochondrial calcium dysregulation, we demonstrated that PS-NP exposure impaired mitochondrial function by promoting calcium influx, which is mediated by the increased formation of mitochondria-associated endoplasmic reticulum membranes (MAMs). This process facilitated calcium transfer through the IP3R3-GRP75-VDAC1 complex. Notably, pharmacological inhibition of calcium flux attenuated PS-NP-induced mitochondrial dysfunction, oxidative stress, and inflammatory responses in HL-1 cardiomyocytes. Collectively, our findings indicate that prepubertal PS-NP exposure triggers cardiac inflammation, which is likely mediated by MAM-dependent mitochondrial calcium overload and subsequent activation of the ROS/JAK1/STAT3 signaling axis.},
}

@article {pmid41360758,
year = {2025},
author = {Ma, X and Si, F and Ma, J and Feng, C and Wang, Y and Wang, L and Yu, J},
title = {Endoplasmic Reticulum Stress: A Novel Target for the Prevention and Treatment of Hypertension and Its Related Diseases.},
journal = {Journal of cellular and molecular medicine},
volume = {29},
number = {23},
pages = {e70977},
pmid = {41360758},
issn = {1582-4934},
support = {81960086//National Natural Science Foundation of China/ ; 82160089//National Natural Science Foundation of China/ ; 82460086//National Natural Science Foundation of China/ ; CY2021-MS-A13//Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital/ ; YJS-BD-24//Special Fund Project for Doctoral Training of the Lanzhou University Second Hospital/ ; PR0124002//International science and technology cooperation base/ ; },
mesh = {Humans ; *Endoplasmic Reticulum Stress/drug effects ; *Hypertension/prevention & control/drug therapy/metabolism/pathology ; Animals ; Oxidative Stress/drug effects ; Taurochenodeoxycholic Acid/therapeutic use/pharmacology ; Renin-Angiotensin System/drug effects ; Antihypertensive Agents/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Molecular Targeted Therapy ; Phenylbutyrates/therapeutic use/pharmacology ; },
abstract = {Endoplasmic reticulum stress (ERS) emerges as a critical pathophysiological nexus in hypertension and related cardiovascular diseases. Chronic ERS activation via the IRE1α-XBP1, ATF6, and PERK pathways drives vascular endothelial dysfunction (reduced NO bioavailability, increased ET-1), renin-angiotensin system (RAS) hyperactivation, sympathetic overactivation, and vascular smooth muscle cell (VSMC) maladaptive proliferation/apoptosis, collectively promoting hypertension progression and end-organ damage. Pharmacological targeting of ERS demonstrates therapeutic promise: chemical chaperones 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA) stabilise proteostasis, reduce oxidative stress, and inhibit apoptosis; antioxidants N-acetylcysteine (NAC) and melatonin attenuate ERS-oxidative stress crosstalk. Notably, conventional antihypertensives-ACE inhibitors and angiotensin receptor blockers (ARBs)-exert ancillary benefits by suppressing ERS beyond their primary RAS blockade. Preclinical evidence supports the efficacy of these strategies in reversing hypertensive pathophysiology. Future research must prioritise isoform-selective ERS modulator development, validation in human trials, biomarker discovery, and elucidating ERS roles in therapy-induced hypertension. Targeting ERS represents a transformative mechanotherapeutic paradigm for precision hypertension management.},
}

Humans
*Endoplasmic Reticulum Stress/drug effects
*Hypertension/prevention & control/drug therapy/metabolism/pathology
Animals
Oxidative Stress/drug effects
Taurochenodeoxycholic Acid/therapeutic use/pharmacology
Renin-Angiotensin System/drug effects
Antihypertensive Agents/therapeutic use/pharmacology
Signal Transduction/drug effects
Molecular Targeted Therapy
Phenylbutyrates/therapeutic use/pharmacology

@article {pmid41360103,
year = {2025},
author = {Yang, CW and Chen, CY and Yen, CH and Shu, CW and Lee, HY and Chang, HW},
title = {Threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-methoxypropanol (THMP) Inhibits Bladder Cancer Cell Proliferation via Oxidative Stress-dependent Apoptosis and DNA Damage.},
journal = {Planta medica},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2752-9897},
pmid = {41360103},
issn = {1439-0221},
support = {KMUH-111-1R55//Kaohsiung Medical University Hospital/ ; KMUH-112-2R57//Kaohsiung Medical University Hospital/ ; KMUH-113-3R49//Kaohsiung Medical University Hospital/ ; MOST 111-2320-B-037-015-MY3//Ministry of Science and Technology/ ; NSTC 113-2324-B-037-027//National Science and Technology Council/ ; TB114009//Kaohsiung Medical University/ ; TC114A04//Kaohsiung Medical University/ ; NSYSU-KMU-114-P15//National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC114A04//Kaohsiung Medical University Research Center/ ; },
abstract = {Many lignans exhibit antiproliferative effects against cancer cells, but it is rarely reported for threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-methoxypropanol (THMP), an edible red-pepper-derived lignan. This study evaluates the antiproliferative effects and mechanism of THMP against bladder cancer cells (BFTC905 and T24) regarding ATP content and flow cytometry assays in parallel with the presence and absence of N-acetylcysteine (NAC), an oxidative stress inhibitor. THMP suppressed bladder cancer cell viability in the ATP assay, which was reverted by NAC. Regarding flow cytometry, THMP triggered subG1 arrest and enhanced annexin V-affinity intensity. This apoptotic response was further supported by the finding that THMP upregulated the activation of caspases 3, 8, and 9, which is apoptotic signaling. Moreover, oxidative stress was induced by THMP regarding the upregulation of reactive oxygen species (ROS) and mitochondrial superoxide and the exhaustion of glutathione and mitochondrial membrane potential. Regarding γH2AX and 8-hydroxy-2-deoxyguanosine detection, THMP was confirmed to have DNA damage ability. These mechanisms were alleviated by NAC. Overall, THMP is the first report demonstrating the antiproliferative effect against bladder cancer cells and clarifying its oxidative stress-dependent mechanisms.},
}