@article {pmid41708253,
year = {2026},
author = {Wang, P and Zhong, Y and Liu, J and Gao, L and Long, T and Li, Z},
title = {Dietary titanium dioxide particles (E171) promote colitis-associated colorectal cancer development in mice through macrophage-derived S100A8/S100A9secretion mediated by NLRP3/Caspase 1/GSDMD pathway.},
journal = {Chinese journal of natural medicines},
volume = {24},
number = {2},
pages = {215-226},
doi = {10.1016/S1875-5364(26)61092-8},
pmid = {41708253},
issn = {1875-5364},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Calgranulin A/metabolism/genetics ; Mice ; *Titanium/adverse effects/administration & dosage ; *Calgranulin B/metabolism/genetics ; *Macrophages/metabolism/drug effects ; *Caspase 1/metabolism/genetics ; Mice, Inbred C57BL ; RAW 264.7 Cells ; Male ; *Colitis-Associated Neoplasms/chemically induced/genetics/metabolism ; Humans ; Signal Transduction/drug effects ; *Colorectal Neoplasms/genetics/etiology/chemically induced/metabolism ; },
abstract = {Colitis-associated colorectal cancer (CAC) is a major contributor to cancer-related mortality worldwide. Titanium dioxide (TiO2, E171), a widely used food additive, has been insufficiently studied regarding its effects on macrophages within colon tumors during CAC development. In this study, CAC mouse models were used to investigate the biological impact of dietary E171 on macrophages in vivo, while lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cell lines were employed to elucidate the underlying mechanisms in vitro. We found that dietary E171 intake accelerated CAC development, exacerbated inflammatory responses and oxidative stress, and upregulated CAC-associated genes, including S100a8, S100a9, Lcn2, S100a11, Cxcl2, and interleukin-1α (Il-1α). E171 also increased the expression of S100A8, S100A9, NOD-like receptor family pyrin domain-containing 3 (NLRP3), and gasdermin-D N-terminal (GSDMD-N) in macrophages within colon tumors. In inflammatory macrophages, E171 exposure enhanced cell viability, increased reactive oxygen species (ROS) levels, and elevated the expression and secretion of S100A8 and S100A9, consistent with in vivo histological observations. Furthermore, E171-induced secretion of S100A8 and S100A9 in macrophages was suppressed by specific inhibitors, including N-acetylcysteine (NAC, ROS inhibitor), MCC950 (NLRP3 inhibitor), Z-YVAD-FMK (caspase 1 inhibitor), disulfiram (GSDMD inhibitor), and transfection of NLRP3 small interfering ribonucleic acid (siRNA). These results indicate that dietary E171 promotes CAC development by activating macrophages, with S100A8 and S100A9 serving as key mediators, and the NLRP3/caspase 1/GSDMD pathway acting as a critical mechanism.},
}

Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
*Calgranulin A/metabolism/genetics
Mice
*Titanium/adverse effects/administration & dosage
*Calgranulin B/metabolism/genetics
*Macrophages/metabolism/drug effects
*Caspase 1/metabolism/genetics
Mice, Inbred C57BL
RAW 264.7 Cells
Male
*Colitis-Associated Neoplasms/chemically induced/genetics/metabolism
Humans
Signal Transduction/drug effects
*Colorectal Neoplasms/genetics/etiology/chemically induced/metabolism

@article {pmid41704764,
year = {2026},
author = {Huang, X and Meng, Y and Song, J and Zhu, Y and Li, J and Xi, Y and Peng, X and Xiong, Y},
title = {KNSTRN knockdown impairs autophagy flux to inhibit bladder cancer progression.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114734},
pmid = {41704764},
issn = {2589-0042},
abstract = {Bladder cancer (BLCA) is a common malignant tumor of the urinary system. Kinetochore-localized astrin-binding protein (KNSTRN) has been implicated in the initiation and progression of multiple cancers. Furthermore, abnormal autophagy levels have been shown to significantly impact tumor development. However, the mechanism by which KNSTRN regulates autophagy in BLCA remains unclear. This study reveals that KNSTRN knockdown inhibits autophagy flux in BLCA. The mechanism involves ROS-dependent disruption of lysosomal function upon KNSTRN knockdown, thereby impeding autophagosome-lysosome fusion. Clioquinol restores lysosomal activity by regulating lysosomal pH, subsequently reestablishing autophagy flux. The ROS scavenger N-acetylcysteine (NAC) reverses lysosomal dysfunction and reactivates the autophagic flux. Furthermore, the autophagy activator rapamycin (Rapa) effectively counteracts KNSTRN knockdown-induced cell death in both in vitro and in vivo experiments. Collectively, we demonstrate that KNSTRN knockdown induces intracellular ROS accumulation and lysosomal dysfunction, thereby disrupting autophagic flux and inhibiting BLCA progression.},
}

@article {pmid41701447,
year = {2026},
author = {Sabry, S and Ammar, MK and Taeima, M and Nassar, N and ElFiky, A and Saleh, A},
title = {Preventing Contrast-Induced Acute Kidney Injury in Egyptian Patients Undergoing Coronary Angiography: A Randomized Controlled Trial.},
journal = {Clinical drug investigation},
volume = {},
number = {},
pages = {},
pmid = {41701447},
issn = {1179-1918},
abstract = {BACKGROUND AND OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) observed after coronary angiography (CAG) requires preventive strategies guided by clinical judgment. Evidence is still lacking regarding the prevention of CI-AKI in patients undergoing coronary angiography. This study aimed to compare the effect of a high dose of N-acetylcysteine (NAC) plus preprocedural hydration, a high dose of atorvastatin (HDS) plus preprocedural hydration, or preprocedural hydration alone on the prevention of CI-AKI in patients undergoing elective coronary angiography.

METHODS: A prospective multi-armed randomized comparative study was conducted on elective patients undergoing CAG. Patients were randomly assigned to either control group [n = 40], who received hydration with 0.9% saline started just before contrast media injection and continued for 12 h at a rate 1.0 mL/kg/min after angiography; NAC group [n = 40], who received oral NAC 1200 mg daily started 5 days before angiography and good hydration; or HDS group [n = 40], receiving one oral dose of atorvastatin 80 mg 24 h before angiography and good hydration. CI-AKI was defined as an increase in serum creatinine of > 25% of baseline or an absolute increase of 0.5 mg/dL above baseline after 48 h. Incidence of CI-AKI and incidence of complications were assessed for all groups.

RESULTS: The study included 120 patients. The incidence of CI-AKI was [32.5%] in the control group, [20%] in the NAC group, and [12.5%] in the HDS group. The incidence of CI-AKI was significantly lower in the high-dose statin group compared with the control group (risk ratio = 1.658; 95% CI 1.050-2.433). In-hospital clinical outcomes showed no statistical significance among the three groups.

CONCLUSIONS: Both NAC and high-dose statins may reduce CI-AKI incidence in patients undergoing CAG, with statins showing more promising results. These findings support prophylactic strategies for CI-AKI prevention in high-risk patients undergoing CAG. In-hospital outcomes were comparable.

CLINICAL TRIAL REGISTRATION: Clinical-Trials.gov (ID; NCT06139952, Date; December 2023).},
}

@article {pmid41700562,
year = {2026},
author = {Gregory, E and Wilkinson, EP and Leyngold, I},
title = {N-acetylcysteine and Vitamin C oral antioxidant therapy for teprotumumab-related hearing dysfunction: case series and review of literature.},
journal = {Orbit (Amsterdam, Netherlands)},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/01676830.2025.2608253},
pmid = {41700562},
issn = {1744-5108},
abstract = {We report three cases of successful treatment of teprotumumab-related hearing dysfunction with N-acetylcysteine (NAC) and ascorbic acid (Vitamin C). To investigate NACs effectiveness in the treatment of other types of auditory symptoms through a review of available literature. Three patients with thyroid eye disease (TED) developed symptoms of ear fullness and hearing loss during infusions of teprotumumab. Audiogram revealed above-normal pure tone average hearing threshold frequencies. They were treated with once-daily oral administration of 600 mg N-acetyl cysteine and 500 mg ascorbic acid (Vitamin C). All patients experienced nearly complete resolution of their ear symptoms prior to completing their teprotumumab therapy. They continued to remain symptom-free throughout the remaining teprotumumab infusions and onwards. This study showcases that antioxidant therapy with N-acetylcysteine and Vitamin C appears to be a promising, safe, and inexpensive potential treatment option for teprotumumab-related hearing dysfunction in our patient group.},
}

@article {pmid41686281,
year = {2026},
author = {Moon, UY and Kim, YE and Nguyen, HD and Choi, HJ},
title = {CREB2 Functions as a Central Mediator of Oxidative Neuronal Death Triggered by Microglial Glutamate Release Under Neuroinflammatory Conditions.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01695-w},
pmid = {41686281},
issn = {1573-6830},
support = {2710086662/RS-2025-02213662//Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare/ ; RS-2023-00246655 and RS-2024-00356135//National Research Foundation of Korea/ ; },
abstract = {Glutamate-induced oxidative cytotoxicity is a major driver of neuronal loss in neurodegenerative diseases, yet the upstream transcriptional regulators linking oxidative stress to neuronal death remain unclear despite the known involvement of the p53-GADD45α pathway. CREB2 (ATF4) is a stress-responsive transcription factor, but its role in microglia-mediated oxidative neurotoxicity has not been fully defined. Here, we investigated CREB2 function in oxidative glutamate toxicity using HT22 hippocampal neurons, primary mouse hippocampal cells, and a kainic acid (KA)-injected rat model. Oxidative stress was induced by glutamate, intracellular ROS levels were quantified with DCFDA, and the antioxidant N-acetylcysteine (NAC) was used to confirm oxidative dependency. Microglia-derived glutamate was assessed by stimulating BV2 cells with lipopolysaccharide (LPS) and applying glutamate-containing conditioned medium (LPS-CM) to HT22 cells. Exogenous glutamate robustly increased CREB2 expression in HT22 and primary neurons, accompanied by ROS accumulation and cell death, whereas NAC suppressed these effects. Inhibition of p53 by siRNA or pifithrin-α (PFT-α) attenuated glutamate-induced CREB2 upregulation, and CREB2 knockdown blocked GADD45α induction and protected neurons. In Vivo, KA injection caused robust CREB2 upregulation in the damaged CA3 region. Importantly, conditioned medium from LPS-activated BV2 microglia increased CREB2 expression and ROS levels in HT22 cells in an NAC-sensitive manner, supporting a glutamate-associated oxidative mechanism rather than receptor-mediated excitotoxicity. Collectively, these results suggest that CREB2 functions between upstream p53 signaling and downstream GADD45α activation as a redox-sensitive mediator of oxidative neuronal death, and may represent a potential therapeutic target in neurodegenerative diseases associated with oxidative stress and neuroinflammation.},
}

@article {pmid41683511,
year = {2026},
author = {Hikisz, P and Adamus-Grabicka, AA and Budzisz, E},
title = {Multifaceted Anticancer Activity of Flavanone/Chromanone Intermediates for Five-Membered Heterocyclic Derivatives: Targeting Oxidative Stress, Apoptosis, and MAPK Signaling in Colorectal Cancer.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {3},
pages = {},
doi = {10.3390/molecules31030534},
pmid = {41683511},
issn = {1420-3049},
support = {503/3-066-02/503-31-001//Medical University of Lodz/ ; 2024/08/X/NZ7/01232//National Science Center/ ; 2023/07/X/NZ3/01404//National Science Center/ ; },
mesh = {Humans ; *Apoptosis/drug effects ; *Oxidative Stress/drug effects ; *Flavanones/pharmacology/chemistry ; *Colorectal Neoplasms/metabolism/drug therapy/pathology ; *Antineoplastic Agents/pharmacology/chemistry ; Cell Line, Tumor ; *MAP Kinase Signaling System/drug effects ; Reactive Oxygen Species/metabolism ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; *Heterocyclic Compounds/pharmacology/chemistry ; },
abstract = {This study explores the multifaceted anticancer mechanisms of flavanone analogues and spiropyrazoline condensed with flavanone ring against colorectal cancer (CRC) cell lines. Five-membered heteroaromatic scaffolds, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. Building upon previous findings, we investigated three lead derivatives (1, 3, and 5) with potent antiproliferative activity (IC50 < 35 μM). The compounds induced pronounced oxidative stress, evidenced by increased lipid peroxidation and reduced membrane fluidity, primarily within the hydrophobic layers of cell membranes. Preincubation with the antioxidant N-acetylcysteine (NAC) significantly attenuated these effects, confirming the pivotal role of reactive oxygen species (ROS) in their cytotoxicity. Mechanistic studies revealed that the derivatives triggered intrinsic apoptosis, characterized by the cleavage of PARP and the activation of caspase-9 and caspase-3. Furthermore, the compounds modulated key signaling pathways involved in cell survival and proliferation. Specifically, they inhibited the pro-oncogenic ERK1/2 MAPK pathway while inducing cell line-dependent alterations in p38 and JNK activity. Concurrently, all derivatives reduced the level of the transcription factor Nrf2, a master regulator of antioxidant defense and a mediator of chemoresistance in CRC. Collectively, these findings indicate that flavanone/chromanone derivatives exert their anticancer activity through a synergistic mechanism involving ROS generation, disruption of redox homeostasis, inhibition of Nrf2 signaling, and modulation of MAPK-dependent apoptotic pathways. These results highlight the therapeutic potential of flavanone-based compounds and their spiropyrazoline analogues as multifunctional anticancer agents targeting oxidative stress and survival signaling in colorectal cancer.},
}

Humans
*Apoptosis/drug effects
*Oxidative Stress/drug effects
*Flavanones/pharmacology/chemistry
*Colorectal Neoplasms/metabolism/drug therapy/pathology
*Antineoplastic Agents/pharmacology/chemistry
Cell Line, Tumor
*MAP Kinase Signaling System/drug effects
Reactive Oxygen Species/metabolism
Cell Proliferation/drug effects
Cell Survival/drug effects
*Heterocyclic Compounds/pharmacology/chemistry

@article {pmid41681844,
year = {2026},
author = {Rodriguez, V and Villani, A and Sénica, M and Panebianco, C and Pazienza, V and Preto, A},
title = {Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer.},
journal = {Cancers},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/cancers18030369},
pmid = {41681844},
issn = {2072-6694},
support = {ID. 23006 project//Associazione Italiana Ricerca sul Cancro (AIRC) under IG 2019/ ; UIDB/04050/2020//Fundação para a Ciência e Tecnologia/ ; UID/04050//Centro de Biologia Molecular e Ambiental/ ; },
abstract = {BACKGROUND: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota's role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC).

METHODS: Cell viability assays and IC50 determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry.

RESULTS: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine's impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells.

CONCLUSIONS: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC.},
}

@article {pmid41678124,
year = {2026},
author = {Batsaikhan, T and Lee, HS and Yang, H and Ferdushi, R and Key, J and Seo, YJ},
title = {Therapeutic Effects of N-Acetylcysteine-Primed, Iron Oxide Nanoparticle-Enhanced Mesenchymal Stem Cell Exosomes in Ototoxicity Hearing Loss.},
journal = {Tissue engineering and regenerative medicine},
volume = {},
number = {},
pages = {},
pmid = {41678124},
issn = {2212-5469},
abstract = {BACKGROUND: Sensorineural hearing loss caused by ototoxic agents remains irreversible due to the limited regenerative capacity of cochlear hair cells. Exosome-based therapies derived from mesenchymal stem cells (MSCs) offer a promising, cell-free alternative to protect auditory structures by modulating oxidative stress and inflammation. In this study, we evaluated the therapeutic potential of exosomes isolated from nanoparticle (NP) labeled, N-acetylcysteine primed tonsil-derived mesenchymal stem cells (T-MSCs), hereafter referred to as SPISOME-NAC, in kanamycin-induced ototoxicity models.

METHODS: T-MSCs were labeled with positively charged PLGA-PEI clustered SPIONs, with or without NAC pretreatment. Antioxidant enzyme activity (SOD, CAT, GSH), ROS levels, and PRDX1 expression were assessed in vitro. Exosomes were isolated and analyzed via nanoparticle tracking analysis. Their therapeutic efficacy was evaluated in both ex vivo cochlear explants and mouse model of kanamycin-induced ototoxicity. Hair cell survival was quantified via Myosin VIIa immunostaining, and auditory function was assessed using auditory brainstem responses (ABR). Pro-inflammatory cytokines (TNF-α, IL-1, IL-6) were measured via qRT-PCR.

RESULTS: NAC pretreatment significantly enhanced cell viability, increased GSH activity, and reduced intracellular ROS and PRDX1 levels in NP-labeled T-MSCs. Exosomes derived from NAC-pretreated cells (SPISOME-NAC) conferred superior protection to cochlear hair cells, particularly in the basal turn, and significantly improved hearing thresholds in vivo. Furthermore, SPISOME-NAC treatment downregulated inflammatory cytokines in cochlear tissue.

CONCLUSION: SPISOME-NAC exhibit enhanced antioxidant and anti-inflammatory properties, providing functional protection in an ototoxicity-induced hearing loss model. By preventing ROS-mediated mitochondrial damage and apoptosis in cochlear hair cells, NAC interrupts a key pathogenic mechanism in ototoxicity, preserving auditory structure and function. These findings support NAC-primed exosomes as a novel therapeutic strategy for sensorineural hearing loss.},
}

@article {pmid41677644,
year = {2026},
author = {Khamineh, Y and Panahi-Alanagh, S and Zolghadri, S and Mavaddatiyan, L and Ryszkiel, I and Stanek, A and Talkhabi, M},
title = {Effects of N-Acetylcysteine and Alpha-Ketoglutarate on OVCAR3 Ovarian Cancer Cells: Insights from Integrative Bioinformatics and Experimental Validation.},
journal = {Cells},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/cells15030281},
pmid = {41677644},
issn = {2073-4409},
mesh = {Humans ; Female ; *Acetylcysteine/pharmacology ; *Ovarian Neoplasms/pathology/genetics/drug therapy ; *Ketoglutaric Acids/pharmacology ; Cell Line, Tumor ; *Computational Biology/methods ; Apoptosis/drug effects ; Cell Movement/drug effects ; Cell Survival/drug effects ; Cell Proliferation/drug effects ; Protein Interaction Maps/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; },
abstract = {Ovarian cancer remains one of the leading causes of cancer-related mortality among women, underscoring the need for novel combination strategies that effectively inhibit tumor cell growth while limiting adverse effects. N-acetylcysteine (NAC) and alpha-ketoglutarate (AKG) are biologically active compounds with reported anticancer properties; however, their combined effects in ovarian cancer are not well characterized. In this study, we applied an integrative approach combining network pharmacology analysis with in vitro experiments to investigate the effects of NAC and AKG on OVCAR3 ovarian cancer cells. Common molecular targets of NAC and AKG were identified by intersecting predicted compound targets with ovarian cancer-associated genes, followed by protein-protein interaction network construction and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Experimental validation assessed the effects of NAC and AKG, alone and in combination, on cell viability, apoptosis, migration, and clonogenic capacity. Network analysis identified 70 shared target genes enriched in pathways related to apoptosis, cellular stress responses, and cell migration. In vitro experiments demonstrated that combined treatment with NAC (10 mM) and AKG (100 µM) significantly reduced cell viability, increased apoptotic cell death, and markedly suppressed cell migration and colony formation compared with single-agent treatments. Overall, these findings indicate that the combination of NAC and AKG exerts enhanced inhibitory effects on ovarian cancer cell growth and motility in vitro.},
}

Humans
Female
*Acetylcysteine/pharmacology
*Ovarian Neoplasms/pathology/genetics/drug therapy
*Ketoglutaric Acids/pharmacology
Cell Line, Tumor
*Computational Biology/methods
Apoptosis/drug effects
Cell Movement/drug effects
Cell Survival/drug effects
Cell Proliferation/drug effects
Protein Interaction Maps/drug effects
Gene Expression Regulation, Neoplastic/drug effects

@article {pmid41677304,
year = {2026},
author = {Higazy, D and Vergauwe, F and Coenye, T and Ciofu, O},
title = {Evolutionary adaptations of Pseudomonas aeruginosa biofilms to ciprofloxacin and antioxidant co-treatment in synthetic sputum medium.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0314925},
doi = {10.1128/spectrum.03149-25},
pmid = {41677304},
issn = {2165-0497},
abstract = {UNLABELLED: Antimicrobial resistance (AMR) is a growing public health concern, particularly in biofilm-related infections, where microbial aggregates display high levels of tolerance. Oxidative stress has been hypothesized to accelerate the development of resistance, whereas antioxidants (AOs) may mitigate this process. In this study, we investigated the impact of AOs on the evolution of ciprofloxacin (CIP) resistance in Pseudomonas aeruginosa PAO1 using synthetic cystic fibrosis sputum medium (SCFM2), which mimics the physiochemical conditions of cystic fibrosis (CF) respiratory infections. Experimental evolution was performed over six passages with CIP alone or in combination with edaravone (ED), N-acetyl-cysteine (NAC), or thiourea (THU). Population analysis profiles and minimum inhibitory concentration (MIC) assays demonstrated that CIP treatment produced high-level resistance (MIC 8-32 mg/L), whereas CIP + AO treatments markedly suppressed resistance development (MIC 0.75-2 mg/L). Whole-genome sequencing revealed distinct mutational patterns. CIP-treated isolates carried mutations in mexR and nalC (efflux pump regulators), and gyrA (fluoroquinolone target), consistent with elevated resistance, along with additional mutations in rocR and dnaX. In contrast, evolved isolates in the presence of CIP + AO harbored nfxB mutations associated with lower resistance, while CIP + ED uniquely produced a mutation in parS. These findings support the role of reactive oxygen species (ROS) in driving resistance evolution under CF-like conditions and suggest that antioxidants can suppress this process, providing a potential strategy for limiting antimicrobial resistance in biofilm-associated infections.

IMPORTANCE: Fighting antimicrobial resistance (AMR) is one of the greatest health challenges of our time. To find new ways to stop it, we need to better understand how resistance develops. Our study suggests that antioxidants may help slow down the process that allows bacteria to become resistant. We also show that resistance develops more quickly, and in a different way, when bacteria grow in conditions that resemble the human body rather than in standard laboratory media. In particular, the synthetic sputum medium promoted the formation of aggregated biofilms-sticky communities of cells that often occur in chronic and hard-to-treat infections.},
}

@article {pmid41559638,
year = {2026},
author = {Li, H and Shen, H and Duan, X and Guo, M and Liu, X},
title = {Efficacy and safety of anti-inflammatory drug-assisted treatment of symptoms in patients with schizophrenia: a meta-analysis.},
journal = {BMC psychiatry},
volume = {26},
number = {1},
pages = {161},
pmid = {41559638},
issn = {1471-244X},
support = {Grant No. 202101BA070001-119//the Special Basic Research Cooperative Research Programs of the Yunnan Provincial Undergraduate Universities' Association/ ; Grant No. 202305AS350001//the Program for Innovative Research Team of Yunnan Province/ ; Grant No. AT2024002//the Yunnan Province Insect Biomedicine Research and Development Key Laboratory Open Project/ ; },
abstract = {BACKGROUND: Although anti-inflammatory agents have been explored as adjunctive treatments for schizophrenia, findings remain inconsistent. While some meta-analyses suggest benefit, concerns persist regarding methodological heterogeneity, language bias, and the influence of publication bias on reported effect sizes (ES). This updated meta-analysis aims to re-evaluate the efficacy and safety of anti-inflammatory drugs in schizophrenia, with a critical focus on robustness after accounting for these biases.

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating anti-inflammatory drugs as adjunctive therapy in schizophrenia. Databases (PubMed, Embase, Scopus, Web of Science) were searched from inception to December 31, 2024, with restriction to English-language publications. Standardized mean differences (Hedges’s g) were calculated using a random-effects model. Heterogeneity was assessed using I², and publication bias was evaluated via Egger’s test and trim-and-fill analysis. Sensitivity analyses were performed to assess robustness.

RESULTS: Seventy-four RCTs involving 5,484 participants were included. Initial analyses suggested significant benefits for aspirin (ES = 0.64), celecoxib (ES = 0.49), estrogens (ES = 0.59), fatty acids (ES = 0.25), minocycline (ES = 0.38), N-acetylcysteine (NAC; ES = 0.60), monoclonal antibodies (mAbs; ES = 0.49), and pregnenolone (ES = 0.20). However, substantial heterogeneity (I² > 50%) and significant publication bias were detected for several agents, including estrogens (p < 0.001) and minocycline (p = 0.01). Trim-and-fill analysis indicated that the observed effects for estrogens and minocycline were likely inflated, with adjusted ES falling below conventional thresholds for statistical significance in some cases. Sensitivity analyses excluding high-risk-of-bias studies further weakened the evidence for several compounds. No significant benefit was found for statins or varenicline.

CONCLUSION: While some anti-inflammatory agents initially appear beneficial as adjunctive treatments in schizophrenia, these findings are tempered by high heterogeneity, potential language bias (due to exclusive inclusion of English-language studies), and significant publication bias. After correction for these biases, the clinical significance of many reported effects diminishes. Current evidence does not robustly support routine clinical use of these agents outside of research settings. Future large-scale, long-term, and globally representative RCTs with rigorous reporting standards are needed to determine whether any anti-inflammatory strategy offers reproducible and clinically meaningful benefits.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-026-07774-y.},
}

@article {pmid41666086,
year = {2026},
author = {Babayigit, Z and Yiğider, AP and Yiğit, O and Algün Gedik, A and Dumur, S and Uzun, H},
title = {Effect of intratympanic N-acetylcystein (NAC) on vestibulotoxicity model formed with intratympanic gentamicin in Guinea pigs.},
journal = {Acta oto-laryngologica},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/00016489.2025.2600090},
pmid = {41666086},
issn = {1651-2251},
abstract = {BACKGROUND: N-acetylcysteine (NAC) can protect against this damage.

AIM: To evaluate the effect of intratympanic NAC on the vestibulotoxicity model formed with intratympanic gentamicine in guinea pigs.

DESIGN: Experimental Animal Study.

METHODS: Guinea pigs were randomly divided into three groups. Group1 (control), group2 was treated with intratympanic(IT) gentamicin and group3 was treated with IT gentamicin + NAC. A single dose of NAC was applied on the 1st,3rd, and5th days. Cervical-vestibular evoked myogenic potentials (c-VEMP) measurements and blood samples were taken from the guinea pigs on the day 0,10,30.

RESULTS: In group2 on day 10 c-VEMP latency was prolonged and on day 30 c-VEMP responses were lost in half of animals. A partial loss of c-VEMP values was observed in the group3. Serum total antioxidant capacity (TAC) and superoxide dismutase (SOD) activity in group3 (on the 7th and 30th day) were significantly higher than those in the group2. Tissue SOD and glutathione (GSH) were lower, while the malondialdehyde (MDA) and lipid hydroperoxide (LOOH) were the higher in group2.

CONCLUSION: Gentamicin induced loss in c-VEMP responses and NAC played an effective role in reducing this loss which were confirmed by oxidative capacity at tissue and serum level.},
}

@article {pmid41663453,
year = {2026},
author = {Heshmati, ZS and Amiri-Yekta, A and Khosravifar, M and Akbarian, F and Moini, A and Eftekhari-Yazdi, P and Hafezi, M and Afsharian, P},
title = {Administration of N-acetylcysteine influence the expression of apoptotic genes in the granulosa cells of infertile women diagnosed with endometriosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-34202-0},
pmid = {41663453},
issn = {2045-2322},
support = {401000042//Royan Institute for Reproductive Biomedicine, ACECR, Iran/ ; 2447/1400/D//Royan Lotus Charity Foundation, Iran/ ; },
abstract = {Endometriosis is a chronic, multifactorial disorder. Reactive oxygen species (ROS) and oxidative stress (OS) contribute to the development of endometriosis by affecting apoptosis-related genes in granulosa cells. N-acetylcysteine (NAC) is an antioxidant that reduces OS. This randomized controlled trial aimed to investigate the effects of NAC on serum levels of superoxide dismutase (SOD) and total antioxidant capacity (TAC), as well as the expression of apoptotic genes in granulosa cells. Infertile women with endometriosis were enrolled and administered either NAC (1200 mg/day; n = 11) or placebo (n = 14). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum SOD and TAC levels. The expression of Bcl-2, Bax, and Caspase-3 genes in granulosa cells was evaluated by Real-Time Polymerase Chain Reaction. NAC treatment increased serum SOD and TAC levels. Additionally, the expression of pro-apoptotic genes Bax and Caspase-3 in granulosa cells decreased compared to the placebo group, while the expression of the anti-apoptotic gene Bcl-2 increased. We conclude that administration of N-acetylcysteine (NAC) can reduce apoptosis in granulosa cells of women with infertility due to endometriosis.},
}

@article {pmid41661511,
year = {2026},
author = {Appell, MB and Kanan, Y and Malmberg, K and Appidi, T and Khan, M and Campochiaro, PA and Ensign, LM},
title = {A gel-forming antioxidant eye drop for photoreceptor protection in retinitis pigmentosa.},
journal = {Drug delivery and translational research},
volume = {},
number = {},
pages = {},
pmid = {41661511},
issn = {2190-3948},
support = {R01EY031041/EY/NEI NIH HHS/United States ; P30EY001765/EY/NEI NIH HHS/United States ; T32EY007143/EY/NEI NIH HHS/United States ; },
abstract = {Retinitis pigmentosa (RP) is a chronic genetic condition that leads to progressive loss of photoreceptor cells and vision. While gene therapy is available for a small subset of patients with specific mutations, developing a therapeutic that broadly targets the cellular stresses that lead to cell death could address a major unmet need. One such option would be utilizing antioxidant therapies to neutralize reaction oxygen species (ROS) in the retina that underlie RP progression. Here, we describe an approach for delivering the antioxidants N-acetyl cysteine (NAC) or N-acetyl cysteine ethyl ester (NACET) with a gel-forming eye drop previously demonstrated to provide therapeutic drug delivery in the posterior segment in animals. We demonstrated therapeutic protection of photoreceptor structure and function in a chemically-induced rat model of RP (48% increase in photopic b-wave amplitude), as well as some limited protection in an aggressive genetic mouse model (rd10) of retinal degeneration (~ 31% increase in photopic b-wave amplitude) with once daily application. However, antioxidants have inherent stability issues when stored in solution, so we investigated the use of additional excipients to improve stability and retain potency. While a promising approach, future work to address product stability and efficacy in larger eyes is needed for further development.},
}

@article {pmid41659018,
year = {2025},
author = {Spurrier-Best, L and Butcher, D and Blackham-Hayward, E and Kertesz, Z and Chichger, H},
title = {Nicotine-free electronic vape fluid stimulates angiogenic processes in vitro through ARF6-mediated oxidative stress.},
journal = {Frontiers in toxicology},
volume = {7},
number = {},
pages = {1699112},
pmid = {41659018},
issn = {2673-3080},
abstract = {INTRODUCTION: The increase in e-cigarette use in the population has led to substantial interest in the health impacts associated with e-cigarette smoking. E-cigarette smoking represents a key external environmental cell stressor. Whilst there have been several studies to investigate the effect of nicotine-containing e-cigarette fluid, there is still a significant lack of understanding of how nicotine-free e-cigarette smoking can impact individuals. However, preliminary studies indicate that nicotine-free e-cigarette smoking can cause impaired endothelial function in humans.

MATERIALS AND METHODS: In the present study, we therefore used a common brand of nicotine-free e-cigarette and human umbilical vein endothelial cells to assess angiogenic processes in vitro.

RESULTS: We observed a significant upregulation in endothelial cell adhesion, migration and new tube formation with exposure to nicotine-free e-cigarette condensate (eVape) which was abrogated with exposure to the antioxidant, N-acetyl cysteine. Proteome analysis demonstrated that eVape exposure increased expression of the pro-angiogenic factors, angiogpoeitin-2, endoglin (CD105), PIGF and VEGF, as well as the ADP ribosylation factor, ARF6, and ARF6-GEF, ARNO. Chemical inhibition of ARNO reduced eVape-induced oxidative stress, angiogenic processes, and release of angiogpoeitin-2, endoglin (CD105) and VEGF.

DISCUSSION: These findings demonstrate that nicotine-free eVape causes aberrant upregulated angiogenesis in an in vitro model of the human endothelium through ARNO-dependent signalling. This study is the first to demonstrate the molecular mechanisms in response to the cellular stressor, nicotine-free eVape which underlie impaired vascular function.},
}

@article {pmid41657721,
year = {2026},
author = {Peerapen, P and Putpeerawit, P and Boonmark, W and Thongboonkerd, V},
title = {Systematic evaluation and comparison of the in vitro inhibitory activities of dietary supplements against calcium oxalate crystal formation, growth and aggregation: Implications for kidney stone prevention.},
journal = {Current research in food science},
volume = {12},
number = {},
pages = {101326},
pmid = {41657721},
issn = {2665-9271},
abstract = {Kidney stone disease (KSD), particularly calcium oxalate (CaOx) type, remains a global health problem. Many efforts have been made to prevent KSD, including the use of some dietary supplements. However, mechanisms underlying their anti-KSD properties have remained poorly understood, and their relative anti-KSD properties have previously been unknown. Herein, we systematically evaluated and compared the inhibitory effects of five well-known dietary supplements on CaOx crystals. Caffeine (CAF), epigallocatechin-3-gallate (EGCG), N-acetylcysteine (NAC), resveratrol (RES) and trigonelline (TRIG) (at 1, 10 and 100 μM, which are within their physiologic levels in the urine) were subjected to CaOx crystallization, growth and aggregation assays. Degrees of their CaOx crystal-inhibitory activities were then compared. CAF inhibited crystal formation, EGCG inhibited crystal formation and growth, NAC inhibited crystal aggregation, RES inhibited crystal growth, and TRIG inhibited crystal formation and growth. However, RES promoted crystal aggregation and thus served as a dual modulator (acting as an inhibitor and promoter at different steps of stone formation). Almost all of these inhibitory effects were concentration-dependent. Comparing the CaOx-inhibitory activities of these compounds revealed that EGCG was the most potent inhibitor against CaOx crystal formation (with the crystal abundance-inhibitory activity of 85.61 ± 5.12 %), whereas RES was the most potent inhibitor against CaOx crystal growth (with the crystal growth-inhibitory activity of 92.99 ± 1.67 %). NAC was the only inhibitor against CaOx crystal aggregation (with the crystal aggregation-inhibitory activity of 22.97 ± 0.75 %). These data indicate the direct inhibitory effects of various dietary supplements against CaOx crystal formation, growth and aggregation, supporting their roles in KSD prevention.},
}

@article {pmid41654163,
year = {2026},
author = {Thakur, M and Mutyala, D and Amoliga, AA and Kondati, R and Batra, S},
title = {ROS-Driven Rewiring of Hippo-Inflammation-Polycomb Axis by PFOA in 2D and 3D Lung Epithelial Models.},
journal = {Toxicology},
volume = {},
number = {},
pages = {154426},
doi = {10.1016/j.tox.2026.154426},
pmid = {41654163},
issn = {1879-3185},
abstract = {Perfluorooctanoic acid (PFOA), a persistent organic pollutant and prominent member of the per- and polyfluoroalkyl substances (PFAS) family, continues to raise global concern due to its bioaccumulation and potential for chronic human exposure. While hepatic and systemic toxicities of PFOA are well documented, its effects on lung epithelial integrity, particularly at environmentally relevant concentrations, remain incompletely understood. In this study, we investigated the cellular and molecular responses to PFOA in human alveolar lung epithelial cells (A549) cultured under both 2D submerged monolayer and 3D air-liquid interface (ALI) conditions, representing systemic and barrier-relevant exposure models. Cells were exposed to 10-1000nM PFOA for 24h to assess changes in pro-inflammatory mediators, including transcription factors-NF-κB and STAT3, pattern recognition receptors (TLR4 and RAGE), cytokine/chemokine production (IL-6, IL-8, CCL2, CCL5), and damage-associated molecular patterns (HSP70, HMGB1). PFOA also appeared to trigger translational stress responses, including stress granule and P-body formation, along with alterations in Hippo signaling via YAP/TAZ overactivation. PFOA-challenged cells exhibited activation of Polycomb Repressive Complexes and associated silencing histone marks (H3K27me3, H2AK119Ub), along with HDACs and SIRT family members, indicative of a redox-driven Polycomb-mediated gene silencing program. Oxidative stress was identified as the central driver of epigenetic and Hippo pathway disruptions, as observed in cells pre-exposed to 1 mM N-acetylcysteine (NAC). Despite these molecular alterations, epithelial cell migration capacity remains unaffected under acute exposure. Our results provide key mechanistic insights into PFOA-mediated disruption of redox homeostasis, immune signaling, and epigenetic plasticity in A549 cells, as well as identifying biomarkers for future biomonitoring efforts and studying regulatory frameworks.},
}

@article {pmid41654007,
year = {2026},
author = {Dutta, D and Behera, A and Roy, D and Sukla, S and Banerjee, S},
title = {Mechanistic Exploration of Methylglyoxal-Induced Hepatotoxicity Involving Oxidative Stress, Apoptosis, and Gluconeogenic Modulation.},
journal = {Chemico-biological interactions},
volume = {},
number = {},
pages = {111954},
doi = {10.1016/j.cbi.2026.111954},
pmid = {41654007},
issn = {1872-7786},
abstract = {Methylglyoxal (MG) is a precursor of advanced glycation end-products produced during glycolysis. MG accumulation is linked to various pathophysiological conditions through the production of reactive oxygen species (ROS). This investigation uncovers the mechanism of MG-induced hepatotoxicity in vitro and in vivo. We assessed MG's dose- and time-dependent cytotoxicity (0.001-10 μM) in HepG2 cells using the cell viability assay. We examined the protective effects of N-acetylcysteine (NAC) against MG toxicity using MTT reagent, monitoring ROS generation, apoptosis (via flow cytometry), and mitochondrial membrane potential (with JC1 dye staining). For the in vivo study, BALB/c mice received MG (290 mg/kg and 400 mg/kg) at 6 h and 14 h intervals to induce hepatotoxicity. We conducted liver histopathology and protein expression analysis for apoptotic markers (Bax, Bcl-2, and caspase-3) and gluconeogenesis regulators (SIRT1, PGC1α, and glucose 6-phosphatase or G6Pase) in both cell lines and liver tissues. MG caused significant dose- and time-dependent toxicity in HepG2 cells by promoting cell death, increasing ROS and apoptosis, and altering the mitochondrial membrane potential at 5 μM. NAC (5 and 10 mM) protected against MG-induced toxicity. In mice, MG led to elevated spleen and liver weight, aspartate transferase (AST), alanine transaminase (ALT), glucose, malondialdehyde, and decreased superoxide dismutase levels. MG upregulated pro-apoptotic and gluconeogenic proteins in HepG2 cells, while NAC significantly reduced their levels. MG also increased the expression of proteins involved in apoptosis and gluconeogenesis. MG-induced caspase-dependent hepatotoxicity was mediated by the production of ROS and the activation of gluconeogenesis via SIRT1-Dependent PGC1α activation.},
}

@article {pmid41653207,
year = {2026},
author = {Zhang, M and Guan, C and Sheng, G and Ding, Z and Zhao, Y and Zhao, G and Li, W and Hu, Z and Peng, Y and Zheng, J},
title = {Pyrazinamide-induced hepatotoxicity mediated by aldehyde oxidase and xanthine oxidase.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {41653207},
issn = {1432-0738},
support = {ZK[2023]319//Guizhou Provincial Science and Technology Department/ ; },
abstract = {Pyrazinamide (PZA) has been approved for the treatment of tuberculosis in clinical practice. However, its adverse effects, particularly hepatotoxicity, have raised concerns. The present study aimed at exploring the potential relationship between PZA-induced hepatotoxicity and its metabolites resulting from metabolic activation. Glutathione (GSH) conjugates with confirmed structures were detected in mouse cytosol incubations containing PZA or pyrazinoic acid (POA, a major metabolite of PZA) supplemented with glutathione (GSH). Such GSH metabolites were also observed in both liver homogenates from mice administered with PZA and mouse primary hepatocytes exposed to PZA. Aldehyde oxidase (AO) and xanthine oxidase (XOD) were identified as key enzymes in the metabolic activation of PZA and POA. Both vitamin C (VC) and N-acetylcysteine (NAC) were found to reduce the generation of GSH conjugates derived from PZA and POA in incubation systems. Additionally, VC alleviated the susceptibility of hepatocytes to PZA-induced cytotoxicity. Consecutive administration of PZA for 7 days resulted in a marked elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice, and PZA-derived hepatic protein adduction was detected. Allopurinol administration attenuated the elevated serum ALT and AST in company with a reduction in the formation of GSH conjugates. This work provides solid evidence for the correlation between the metabolic activation of PZA and PZA-induced hepatotoxicity, enhancing the understanding of the underlying mechanisms of PZA toxicity in terms of molecular chemical structure.},
}

@article {pmid41520042,
year = {2026},
author = {Liu, PK and Chi, YC and Chang, YC and Lin, YH and Chen, CY and Liu, C and Tyan, YC and Chang, KC},
title = {Quercetin attenuates high glucose-induced VEGFA expression in ARPE-19 cells by inhibiting ROS generation, p38 MAPK phosphorylation, and NF-κB activation.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {4987},
pmid = {41520042},
issn = {2045-2322},
support = {114-2314-B-037-115//NSTC/ ; 113-3R45//Kaohsiung Medical University Chung-Ho Memorial Hospital/ ; P30-EY008098/GF/NIH HHS/United States ; unrestricted research grant//Research to Prevent Blindness/ ; },
abstract = {UNLABELLED: Hyperglycemia-driven oxidative stress and inflammatory signaling in retinal pigment epithelium (RPE) promote overexpression of vascular endothelial growth factor A (VEGFA), contributing to the pathogenesis of diabetic retinopathy (DR). Quercetin, a dietary flavonoid with antioxidant and anti-inflammatory properties, has not been fully evaluated for its ability to counteract high glucose–induced VEGFA upregulation in RPE. Here, ARPE-19 cells were exposed to high glucose (30 mM) with or without quercetin (5 or 20 µM) treatment. VEGFA expression was measured by qPCR and ELISA; intracellular reactive oxygen species (ROS) were assessed using a DCFH-DA probe; and pathway activation was examined by immunoblotting for p38 MAPK and ERK1/2 phosphorylation, IκBα stability, and NF-κB p65 nuclear translocation. N-acetylcysteine (NAC) served as an antioxidant control, and cell viability was monitored using the CCK-8 assay. Quercetin at non-cytotoxic concentrations significantly suppressed high glucose–induced VEGFA mRNA and protein expression, reduced ROS accumulation, and attenuated p38 MAPK phosphorylation without altering ERK1/2 activation. Quercetin also prevented IκBα degradation and diminished p65 nuclear translocation, indicating inhibition of NF-κB signaling. These findings support a model in which quercetin mitigates hyperglycemia-induced VEGFA upregulation in RPE cells at least in part by modulating a ROS–p38 MAPK–NF-κB axis, while not excluding contributions from other glucose- and ROS-sensitive pathways. Quercetin may therefore represent a readily accessible adjunctive strategy to address oxidative stress, inflammation, and VEGFA dysregulation in DR, warranting further in vivo validation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-35409-5.},
}

@article {pmid41642676,
year = {2026},
author = {Anandakrishnan, A and O'Halloran, A and Diamond, T},
title = {Successful Heat Stroke-Induced Pediatric Acute Liver Failure Treatment With N-Acetylcysteine Case Report.},
journal = {Critical care explorations},
volume = {8},
number = {2},
pages = {e1371},
doi = {10.1097/CCE.0000000000001371},
pmid = {41642676},
issn = {2639-8028},
mesh = {Humans ; *Acetylcysteine/therapeutic use ; *Heat Stroke/complications ; Male ; Child ; *Liver Failure, Acute/drug therapy/etiology ; *Free Radical Scavengers/therapeutic use ; },
abstract = {BACKGROUND: Previously healthy children are at risk of developing exertional heat stroke when experiencing extreme heat. Pediatric clinicians in primary care, emergency department, and critical care settings should be versed in the management of complications of exertional heat stroke. Pediatric acute liver failure (PALF) in the setting of heat stroke is rarely reported in published literature.

CASE SUMMARY: A 9-year-old male presented with heat stroke-induced PALF. He initially presented to an emergency department for altered mental status. During his clinical course, despite appropriate identification and initial treatment of exertional heat stroke, his symptoms progressed, including ongoing agitation, hepatic encephalopathy, coagulopathy, and severe transaminase elevation meeting clinical criteria for PALF.

CONCLUSIONS: He was treated with N-acetylcysteine (NAC) with resolution of his PALF without complications. In this article, we review the patient's clinical course, the rationale for treatment with NAC, and the management of heat stroke-induced PALF.},
}

Humans
*Acetylcysteine/therapeutic use
*Heat Stroke/complications
Male
Child
*Liver Failure, Acute/drug therapy/etiology
*Free Radical Scavengers/therapeutic use

@article {pmid41642111,
year = {2026},
author = {Dos Santos, IWR and Souza-Monteiro, D and Frazão, DR and da Silva, ZAL and de Moura, JDM and Cruz, JN and Collares, FM and de Souza-Rodrigues, RD and Cintra, LTÂ and Lima, RR},
title = {N-Acetylcysteine Reduces Alveolar Bone Loss and Mitigates Systemic Oxidative Damage in Rats With Apical Periodontitis.},
journal = {International endodontic journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/iej.70108},
pmid = {41642111},
issn = {1365-2591},
support = {307747/2025-5//Científico e Tecnológico (CNPq, Brazil) of the Brazilian Ministry of Science, Technology and Innovation/ ; 408329/2022-0//Científico e Tecnológico (CNPq, Brazil) of the Brazilian Ministry of Science, Technology and Innovation/ ; 404431/2024-0//Científico e Tecnológico (CNPq, Brazil) of the Brazilian Ministry of Science, Technology and Innovation/ ; 400706/2024-5//Científico e Tecnológico (CNPq, Brazil) of the Brazilian Ministry of Science, Technology and Innovation/ ; 409576/2025-5//Científico e Tecnológico (CNPq, Brazil) of the Brazilian Ministry of Science, Technology and Innovation/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil), Ministry of Education/ ; 406436/2022-3//National Institute of Science and Technology in 3D Printing and Advanced Materials Applied to Human and Veterinary Health/ ; },
abstract = {AIM: This study aimed to evaluate the effects of N-acetylcysteine (NAC) supplementation in apical periodontitis (AP) induced in rats.

METHODOLOGY: Eighteen male Wistar rats were randomly assigned to three groups: control, AP, and AP plus NAC. NAC was administered by oral gavage (100 mg/kg/day), beginning 1 day after lesion induction and continued daily until the day preceding euthanasia. AP induction was performed by exposing the dental pulp of the lower first molars bilaterally, maintaining this condition for 28 days. After this period, the animals were euthanized, and the following biological materials were collected: blood (for systemic oxidative stress analysis) and hemimandibles for histopathological and histochemical, and micro-computed tomography analyses, aiming to measure bone quality parameters and periapical volume. Statistical analyses were performed using one-way ANOVA and Tukey's post hoc test. In addition, correlation analyses and multivariate analyses of variance (MANOVA) were performed on the biochemical parameters.

RESULTS: The study results showed that animals supplemented with NAC had greater preservation of bone quality parameters and a reduction in periapical volume progression when compared to the only apical periodontitis group. Additionally, in the analysis of systemic oxidative stress, supplemented animals showed higher antioxidant parameter levels and lower oxidant levels compared to non-supplemented animals, which also showed reduced preservation of bone collagen content.

CONCLUSIONS: The study findings suggest that NAC supplementation promoted greater preservation of bone quality, reduced periapical volume development, and modulation of endogenous antioxidant and oxidant aspects. This indicates that NAC can decrease local and systemic damage caused by AP, highlighting its potential as an adjunctive agent in processes involving systemic oxidative stress and the preservation of biological structures.},
}

@article {pmid41637640,
year = {2026},
author = {Pandey, AM and Zhou, R and Singh, D and Li, F and He, M and Le, A and Herdrich, J and Chen, Y and Shah, R and Adusei-Poku, S and Rohlwing, NJ and Koo, J and Ong, ZY and Oldfield, E},
title = {Antifungal Activity of Lipophilic Bisphosphonates.},
journal = {ACS infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsinfecdis.5c00838},
pmid = {41637640},
issn = {2373-8227},
abstract = {We investigated the activity of a series of 75 lipophilic bisphosphonates against Candida glabrata. Thirty-six compounds had MIC < 1 μg/mL, 18 had MIC < 0.5 μg/mL, and 2 had MIC = 0.13 μg/mL, comparable to amphotericin B and caspofungin. The lipophilic bisphosphonates were ∼20-fold more potent against C. glabrata than the most potent hydrophilic bisphosphonate, zoledronate. The most active compounds were pyridinium bisphosphonates followed by imidazolium bisphosphonates, while aryl bisphosphonates were less active. Several compounds had selectivity index values against a human cell line in the 1000-3600 range, the most selective compounds being para-substituted pyridinium bisphosphonates. We also found similar activity against a caspofungin-resistant FKS2 (F659S) mutant. Some combinations of lipophilic bisphosphonates had synergistic activity with FICI values in the ∼0.3-0.5 range, and similar synergies were observed with fluconazole, implicating ergosterol biosynthesis inhibition leading to compromised membrane structure and function. Cell growth inhibition was rescued by ascorbic acid, glutathione, and N-acetyl cysteine, indicating a ROS-based killing mechanism. There was also synergy with other antifungals but very strong antagonism with verapamil (FICI ∼4), which blocks calcium channels. Unlike hydrophilic bisphosphonates, which target farnesyl diphosphate synthase, lipophilic bisphosphonates also target squalene synthase, suggesting that the combination of multitargeting bisphosphonates is one origin of the synergistic interactions observed. Given that one of the lipophilic bisphosphonates studied here (BPH-1237) has been shown to have activity against many other human fungal pathogens, combinations with the compounds described here may be of interest as antifungal leads.},
}

@article {pmid40729925,
year = {2026},
author = {Liu, L and Ren, S and Hao, Y and Yue, L and Yue, C and Li, L and Zhang, W and Gao, Z and Hai, X},
title = {Development and validation of a sensitive assay for analysis of D/L-serine in cells using ultra-high performance liquid chromatography-fluorescence detector.},
journal = {Talanta},
volume = {297},
number = {Pt A},
pages = {128634},
doi = {10.1016/j.talanta.2025.128634},
pmid = {40729925},
issn = {1873-3573},
mesh = {*Chromatography, High Pressure Liquid/methods ; o-Phthalaldehyde/chemistry ; Stereoisomerism ; Humans ; Animals ; Acetylcysteine/chemistry ; Spectrometry, Fluorescence/methods ; },
abstract = {The aim of this study was to establish a simple, sensitive, and robust ultra-high performance liquid chromatography coupled with fluorescence detection method (UPLC-FLD) for the determination of chiral D/L-serine in cells. D/L-serine in cells were derivatizated by o-phthalaldehyde (OPA) and N-acetyl-L-cysteine (NAC). Carbocisteine was selected as the internal standard. The derivatives were separated on a C18 column by gradient elution. The excitation and emission wavelengths for fluorescence determination are 340 nm and 450 nm, respectively. The retention time of D-serine and L-serine was 23.3 and 23.9 min respectively, which presented a perfect separation. The accuracy of D-serine and L-serine were ranged from 96.46 % to 109.63 % and 95.50 %-102.20 %, respectively. The precision of D-serine and L-serine were ranged from 4.34 % to 14.56 % and 3.56 %-13.73 %. The limit of quantitation of D-serine and L-serine were 0.1 nmol/mL. The concentration of D/L-serine varies in different cell lines. This method can satisfy the determination of D/L-serine in astrocytes and other cells, which can be used for the study of D/L-serine metabolism and related mechanisms. In short, we have established a simple, stable, reliable and robust method for the determination of D/L-serine in cells. In addition, the D/L-serine levels in different cells were quantified in this study, which can provide a reference for the study of D/L-serine metabolism in cells.},
}

*Chromatography, High Pressure Liquid/methods
o-Phthalaldehyde/chemistry
Stereoisomerism
Humans
Animals
Acetylcysteine/chemistry
Spectrometry, Fluorescence/methods

@article {pmid41632564,
year = {2026},
author = {Zhang, J and Yan, M and Tang, Y and Liu, M and Yao, W and Zhang, Q and Chen, H},
title = {A First-Aid Nanomedicine Endowed with Microenvironment Self-Adaptive Regulation Ability to Facilitate Acute Liver Failure Prophylaxis and Therapy.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c18314},
pmid = {41632564},
issn = {1936-086X},
abstract = {Acute liver failure (ALF) represents a life-threatening medical emergency with high mortality, yet limited treatment is available clinically. Here, we report albumin-biomineralized nonstoichiometric copper sulfide nanoparticles serving as first-aid nanomedicine to combat ALF, conceptualized as NanoAID. The NanoAID exhibits an electron-donor nanoantioxidant property to scavenge reactive oxygen species and concurrent anti-inflammatory capacity to reprogram pro-inflammatory M1 macrophages into anti-inflammatory M2-phenotype, thereby mitigating excessive oxidative and inflammatory stress in ALF lesions. More interestingly, we found Cu ions release under an in situ oxidative stress switch and the resulting H2S gas generation by NanoAID degradation, which further enhance the biosynthesis of intrahepatic antioxidant enzyme SOD1 and the repolarization of M1-to-M2 macrophages, respectively, thereby self-reinforcing ALF therapy. Such microenvironment self-adaptive regulation confers NanoAID with effective prophylactic efficacy and significant ALF survival advantages over the FDA-approved N-acetyl cysteine in multiple animal models, extending the first-aid window to 6 h post APAP intoxication. Transcriptomics results reveal the molecular mechanisms of NanoAID by promoting antioxidative and inhibiting inflammatory pathways, underscoring its great potential as a next-generation first-aid nanomedicine for ALF management.},
}

@article {pmid41630014,
year = {2026},
author = {Ali̇hossei̇ni̇, H and Çolakoğlu, EÇ and Haydardedeoğlu, AE and Özen, D},
title = {N-acetylcysteine reduces serum creatinine, blood urea nitrogen, symmetric dimethylarginine and urine protein to creatinine ratio in cats with chronic kidney disease: a double-blind, placebo-controlled clinical trial.},
journal = {BMC veterinary research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12917-026-05328-8},
pmid = {41630014},
issn = {1746-6148},
abstract = {BACKGROUND: Oxidative stress is considered a significant contributing factor of chronic kidney disease (CKD). To date, there is a paucity of clinical data in the literature regarding the effect of N-Acetylcysteine (NAC) in cats with naturally developing CKD. The aim of the study is to evaluate whether the addition of NAC in the treatment of cats with acute exacerbations of CKD could improve kidney function biomarkers over the use of intravenous fluid therapy alone.

METHODS: A total of 50 client-owned cats were included in the study. The inclusion criteria comprised cats previously diagnosed with azotemic CKD (IRIS stage 2-4) in addition to ultrasonographic evidence of bilaterally decreased renal mass, rough surface contours, and alteration of renal cortical echogenicity. All cats were examined using standard clinical procedures, including clinical examination, blood analyses, abdominal ultrasonography, dipstick urinalysis and urine culture. Computer-generated randomisation was utilised to assign the cats into the following groups: NAC (n:40): N-acetylcysteine (70 mg/kg, diluted in 50 ml 0.9% saline solution, administered intravenously over a period of seven days, and a placebo group (n:10) 50 ml 0.9% saline solution, IV for 7 days. Blood analyses and dipstick urinalysis were repeated on the eighth day of treatment. Between-group differences in baseline age and weight were assessed using the Student's t-test, while sex distribution was evaluated with the Fisher's exact test. Treatment effects across time were analysed using a two-way mixed-design ANOVA, with "Group" and "Time" entered as fixed factors and their interaction term included in the model.

RESULTS: SDMA and creatinine concentrations decreased significantly in both groups, but the concentrations of both were significantly lower in the NAC group after treatment (Day 8 values: SDMA NAC 16.5 ± 1.21 µg/dl versus placebo 27 ± 3.89 µg/dl; P = 0.04 and Creatinine NAC 4.01 ± 0.25 mg/dl versus placebo 6.44 ± 0.9 mg/dl; P < 0.001). UPC and BUN decreased significantly in the NAC group, but no change was observed in the placebo group.

CONCLUSION: The incorporation of NAC into treatment regimens demonstrates potential as a treatment strategy for cats with acute-on-chronic kidney disease.},
}

@article {pmid41624281,
year = {2025},
author = {Pas, D and Oltmanns, H and Meißner, J},
title = {In vitro characterization of antimicrobial efficacy and cytotoxicity of polyvinylpyrrolidone-iodine, N-acetylcysteine, methylglyoxal, and N-chlorotaurine as alternative antimicrobials in treating bovine clinical endometritis.},
journal = {Frontiers in veterinary science},
volume = {12},
number = {},
pages = {1699857},
pmid = {41624281},
issn = {2297-1769},
abstract = {Bovine clinical endometritis (CE) is a common indication for antibiotic use in dairy cows. The increase in bacterial resistance and the aspired decrease in antibiotic use under the One Health concept call for alternatives in treatment. Polyvinylpyrrolidone-iodine (PVP), N-acetylcysteine (NAC), methylglyoxal (MGO), and N-chlorotaurine (NCT) are known substances with antibacterial properties that could potentially serve as those alternatives. In a broth microdilution assay, their efficacy against the common cause of endometritis, Trueperella pyogenes, was investigated. By cytotoxicity testing on a primary bovine endometrial epithelial cell culture, potential adverse effects on cell proliferation, viability, and immune response (IL-6) were examined. While all four substances had an antibacterial effect on T. pyogenes, PVP, MGO, and NCT also showed cytotoxic effects. In contrast, NAC was tolerated well by the cells. In sum, the four tested substances can be considered potential alternatives to antibiotic treatments. Further research is, however, necessary to investigate their toxic effects in ex vivo or in vivo models and to identify effective dosages in animals.},
}

@article {pmid37302633,
year = {2023},
author = {He, H and Li, Q and Fang, L and Yang, W and Xu, F and Yan, Y and Mao, R},
title = {Comprehensive analysis of NAC transcription factors in Scutellaria baicalensis and their response to exogenous ABA and GA3.},
journal = {International journal of biological macromolecules},
volume = {244},
number = {},
pages = {125290},
doi = {10.1016/j.ijbiomac.2023.125290},
pmid = {37302633},
issn = {1879-0003},
mesh = {*Transcription Factors/genetics/metabolism ; *Abscisic Acid/pharmacology/metabolism ; Plant Growth Regulators/pharmacology/metabolism ; Scutellaria baicalensis ; Plant Breeding ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism ; Acetylcysteine/analogs & derivatives ; },
abstract = {The NAC is a plant-specific family of transcription factor that plays important roles in various biological processes. Scutellaria baicalensis Georgi, belongs to the Lamiaceae family and has been widely used as a traditional herb with a wide range of pharmacological activities, including antitumor, heat-clearing, and detoxifying functions. However, no study on the NAC family in S. baicalensis has been conducted to date. In the present study, we identified 56 SbNAC genes using genomic and transcriptome analyses. These 56 SbNACs were unevenly distributed across nine chromosomes and were phylogenetically divided into six clusters. Cis-element analysis identified plant growth and development-, phytohormone-, light-, and stress-responsive elements were present in SbNAC genes promoter regions. Protein-protein interaction analysis was performed using Arabidopsis homologous proteins. Potential transcription factors, including bHLH, ERF, MYB, WRKY, and bZIP, were identified and constructed a regulatory network with SbNAC genes. The expression of 12 flavonoid biosynthetic genes was significantly upregulated with abscisic acid (ABA) and gibberellin (GA3) treatments. Eight SbNAC genes (SbNAC9/32/33/40/42/43/48/50) also exhibited notable variation with two phytohormone treatments, among which SbNAC9 and SbNAC43 showed the most significant variation and deserved further study. Additionally, SbNAC44 displayed a positive correlation with C4H3, PAL5, OMT3, and OMT6, while SbNAC25 had negatively correlated with OMT2, CHI, F6H2, and FNSII-2. This study constitutes the first analysis of SbNAC genes and lays the basis foundation for further functional studies of SbNAC genes family members, while it may also facilitate the genetic improvement of plants and breeding of elite S. baicalensis varieties.},
}

*Transcription Factors/genetics/metabolism
*Abscisic Acid/pharmacology/metabolism
Plant Growth Regulators/pharmacology/metabolism
Scutellaria baicalensis
Plant Breeding
Gene Expression Regulation, Plant
Plant Proteins/metabolism
Acetylcysteine/analogs & derivatives

@article {pmid41620910,
year = {2026},
author = {Bai, X and Luo, Y and Huang, J and Liu, G},
title = {Effect of linezolid combined with N-acetylcysteine on lung function, blood gas and inflammation in patients with severe pneumonia.},
journal = {Pakistan journal of pharmaceutical sciences},
volume = {39},
number = {3},
pages = {803-808},
doi = {10.36721/PJPS.2026.39.3.REG.13264.1},
pmid = {41620910},
issn = {1011-601X},
mesh = {Humans ; *Linezolid/therapeutic use/adverse effects ; *Acetylcysteine/therapeutic use/adverse effects ; Male ; Female ; Middle Aged ; *Pneumonia/drug therapy/physiopathology/blood ; Blood Gas Analysis ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; Aged ; Drug Therapy, Combination ; *Lung/drug effects/physiopathology ; Adult ; Treatment Outcome ; Respiratory Function Tests ; Inflammation/drug therapy ; C-Reactive Protein/metabolism ; },
abstract = {BACKGROUND: Severe pneumonia is a serious lung disease. The continuous and regular administration of antibiotics is currently used for severe pneumonia. However, the single antibiotic may enhance the drug resistance and the overall efficacy is not ideal.

OBJECTIVES: This study aimed to investigate the efficacy and safety of linezolid combined with N-acetylcysteine (NAC) on lung function, blood gas and inflammation in patients with severe pneumonia.

METHODS: Eighty-four severe pneumonia patients were divided into linezolid group and linezolid +NAC group, which received the treatment using linezolid and linezolid combined with NAC for ten days, respectively. The total treatment efficacy was assessed. Before and after treatment, the pulmonary function indexes, blood gas indexes inflammatory response indexes were determined.

RESULTS: Compared with linezolid group, in linezolid +NAC group the disappearance time of cough, sputum and lung rales were shortened, the total effective rate, peak expiratory flow, forced expiratory volume in one second/forced vital capacity, arterial oxygen partial pressure and blood oxygen saturation were increased, the arterial carbon dioxide partial pressure and serum tumor necrosis factor α, interleukin 6 and hypersensitive C-reactive protein levels were decreased (all P < 0.05).

CONCLUSION: In treating severe pneumonia, linezolid combined with NAC can significantly improve the lung function of patients, improve the blood gas indicators and reduce the inflammatory response, thus alleviating the clinical symptoms.},
}

Humans
*Linezolid/therapeutic use/adverse effects
*Acetylcysteine/therapeutic use/adverse effects
Male
Female
Middle Aged
*Pneumonia/drug therapy/physiopathology/blood
Blood Gas Analysis
*Anti-Bacterial Agents/therapeutic use/adverse effects
Aged
Drug Therapy, Combination
*Lung/drug effects/physiopathology
Adult
Treatment Outcome
Respiratory Function Tests
Inflammation/drug therapy
C-Reactive Protein/metabolism

@article {pmid41619526,
year = {2026},
author = {Monti, DA and Zabrecky, G and Kremens, D and Liang, TW and Wintering, NA and Vedaei, F and Navarreto, E and Gupta, M and Steinmetz, A and Bazzan, AJ and Mohammed, F and Newberg, AB},
title = {N-Acetylcysteine is associated with changes in functional connectivity in patients with Parkinson's disease.},
journal = {Parkinsonism & related disorders},
volume = {144},
number = {},
pages = {108216},
doi = {10.1016/j.parkreldis.2026.108216},
pmid = {41619526},
issn = {1873-5126},
abstract = {INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of care only. Participants received pre and post brain imaging with resting Blood Oxygen Level Dependent (BOLD) MRI to measure functional connectivity between key brain regions involved with PD. These findings were compared to changes in PD symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

RESULTS: There were significant differences in the NAC group compared to the control group in functional connectivity measures after NAC. Specifically, there was significantly different functional connectivity between basal ganglia structures and the precuneus, precentral gyrus, postcentral gyrus, and particularly the Rolandic operculum. Changes in the precuneus also correlated with changes in UPDRS scores.

CONCLUSION: The results suggest that NAC may positively affect brain functional connectivity in PD patients, with corresponding positive clinical effects. Larger scale studies are warranted.},
}

@article {pmid41617440,
year = {2026},
author = {Choi, SH and Seo, J and Jeong, SM},
title = {Splicing Factor SF3B4 Suppresses Pancreatic Cancer Growth and Migration by Inhibiting Autophagy.},
journal = {Anticancer research},
volume = {46},
number = {2},
pages = {737-747},
doi = {10.21873/anticanres.17983},
pmid = {41617440},
issn = {1791-7530},
mesh = {Humans ; *Autophagy/drug effects ; *RNA Splicing Factors/metabolism/genetics ; Cell Movement/drug effects ; *Pancreatic Neoplasms/pathology/genetics/metabolism/drug therapy ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Fluorouracil/pharmacology ; *Carcinoma, Pancreatic Ductal/pathology/genetics/metabolism/drug therapy ; Apoptosis/drug effects ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; },
abstract = {BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, characterized by aggressive progression, profound chemoresistance and unique metabolic adaptations such as elevated autophagy. Although the splicing factor SF3B4 has been reported to function as an oncogene in other malignancies, its role in PDAC remains unclear. This study aimed to elucidate the functional and mechanistic significance of SF3B4 in PDAC.

MATERIALS AND METHODS: SF3B4 expression in PDAC was analyzed using patient datasets and experimental models. Functional assays including cell proliferation, colony formation, migration, and autophagy analyses were performed in PDAC cells. Reactive oxygen species (ROS) levels were evaluated. Sensitivity to 5-fluorouracil (5-FU) and apoptotic responses were also evaluated.

RESULTS: SF3B4 acts as a tumor suppressor in PDAC by inhibiting autophagy, a process that this cancer uniquely depends on for survival. SF3B4 overexpression inhibited proliferation, colony formation and migration of PDAC cells. Mechanistically, SF3B4 suppressed autophagic flux, resulting in increased ROS accumulation and subsequent inhibition of tumorigenic phenotypes. Treatment with the antioxidant N-acetylcysteine (NAC) rescued the tumor suppressive effects of SF3B4 overexpression. Moreover, SF3B4 overexpression sensitized PDAC cells to 5-FU, accompanied by enhanced apoptotic responses.

CONCLUSION: SF3B4 is a context-dependent splicing factor that functions as a tumor suppressor in PDAC by regulating autophagy and redox homeostasis. Targeting the SF3B4-autophagy-ROS axis may represent a promising strategy to suppress PDAC progression and overcome chemoresistance.},
}

Humans
*Autophagy/drug effects
*RNA Splicing Factors/metabolism/genetics
Cell Movement/drug effects
*Pancreatic Neoplasms/pathology/genetics/metabolism/drug therapy
Cell Proliferation/drug effects
Cell Line, Tumor
Reactive Oxygen Species/metabolism
Fluorouracil/pharmacology
*Carcinoma, Pancreatic Ductal/pathology/genetics/metabolism/drug therapy
Apoptosis/drug effects
Gene Expression Regulation, Neoplastic
Animals
Mice

@article {pmid41616897,
year = {2026},
author = {Shirpoor, A and Zarrini, Z and Naderi, R},
title = {N-acetyl-cysteine alleviates nandrolone decanoate-induced hippocampal cell apoptosis in rats via reversing protein expressions of S1P1, Akt and FOXO3a signaling pathway.},
journal = {Steroids},
volume = {},
number = {},
pages = {109759},
doi = {10.1016/j.steroids.2026.109759},
pmid = {41616897},
issn = {1878-5867},
abstract = {Illicit use of nandrolone can result in apoptosis in the hippocampus tissue but the underlying mechanism is unknown. The present study evaluated the role of S1P1/Akt/FOXO3a pathway in hippocampus cell apoptosis following exposure to nandrolone decanoate either alone or in combination with N-acetyl-cysteine. Twenty-four male Wistar rats were randomly divided into three groups (n = 8): control, nandrolone (10 mg/kg; intramuscularly; three times per week), and nandrolone + N-acetyl-cysteine (150 mg/kg; intraperitoneally). After six weeks of treatment, the number of apoptotic cells was significantly increased in the nandrolone treated group compared with the control group. Compared to control group, nandrolone group showed significant upregulation of NOX2, iNOS, 8-OHdG, P-FOXO3a/FOXO3a and lactate dehydrogenase (LDH) protein expression in rat hippocampus cells. Conversely, the protein expressions of P-Akt/Akt and S1P1 were significantly downregulated in hippocampus tissue of rats treated with nandrolone compared with control rats. Co-administration of N-acetyl-cysteine with nandrolone significantly reduced the apoptotic index and reversed the expressions of S1P1, P-Akt/Akt and P-FOXO3a/FOXO3a in the hippocampus neurons compared with the nandrolone group. These findings suggest that S1P1/Akt/FOXO3a signaling pathway may at least in part play an important role in the progression of apoptosis induced by nandrolone exposure, providing new insights into the pathogenesis and potential treatment of nandrolone-induced hippocampal damage.},
}

@article {pmid41613139,
year = {2025},
author = {Gao, W and Lin, Z and Bao, Y and Liu, M and Ma, G and Chen, X and Yu, S and Zeng, Y},
title = {A stage specific NETs-related signature in alcoholic steatohepatitis: from molecular subtyping to therapeutic vulnerabilities.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1711388},
pmid = {41613139},
issn = {1664-3224},
mesh = {Humans ; *Fatty Liver, Alcoholic/genetics/immunology/diagnosis/metabolism/drug therapy ; Animals ; Mice ; Matrix Metalloproteinase 7/genetics/metabolism ; *Neutrophils/immunology/metabolism ; Gene Expression Profiling ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Male ; Transcriptome ; Gene Regulatory Networks ; Molecular Docking Simulation ; },
abstract = {BACKGROUND: Alcohol-associated steatohepatitis (ASH) is a globally prevalent liver disease, with robust evidence implicating neutrophil extracellular traps (NETs) as a central pathological phenomenon driving inflammation and progression. However, the core genomic signatures that govern NETs and underlying molecular mechanisms within the ASH microenvironment remain poorly defined.

METHODS: Building on the prominent NETs formation phenomenon in ASH, we established a core pool of NETs-related hub genes through intersection of ASH-derived differentially expressed genes (DEGs), key WGCNA modules, and a curated NETs gene set. From this NET-focused pool, a consensus of three machine learning algorithms (LASSO, SVM, RF) distilled a final diagnostic signature, which was rigorously validated in training and external cohorts via ROC analysis and neural networks. Patient heterogeneity was then investigated using consensus clustering with this signature, followed by immune profiling and functional validation in human and mouse ASH models. Therapeutic potential was explored through drug database enrichment and molecular docking.

RESULTS: A NETs-focused three-gene signature (FOS, MMP7, CXCL6) achieved exceptional diagnostic accuracy for ASH (AUC = 1.00 in training; 0.983 in validation). It stratified ASH into a Metabolic-dominant (C1) subtype and a Pro-inflammatory (C2) subtype, the latter exhibiting higher MMP7/CXCL6, lower FOS, and enriched cytotoxic infiltration. In vivo, FOS rose in acute injury but declined in chronic models and human ASH, whereas MMP7/CXCL6 remained elevated, suggesting a temporal shift from acute FOS-dominant response to sustained MMP7/CXCL6-mediated inflammation. Finally, drug-gene interaction analysis identified several potential therapeutic modulators, including N-acetylcysteine (NAC), with predicted high binding affinities to FOS and MMP7.

CONCLUSION: FOS, MMP7, and CXCL6 constitute a clinically actionable signature capturing the stage-specific dynamics of NETs-driven inflammation in ASH. Beyond its diagnostic and stratifying utility, this signature highlights potential therapeutic avenues for clinical intervention.},
}

Humans
*Fatty Liver, Alcoholic/genetics/immunology/diagnosis/metabolism/drug therapy
Animals
Mice
Matrix Metalloproteinase 7/genetics/metabolism
*Neutrophils/immunology/metabolism
Gene Expression Profiling
Proto-Oncogene Proteins c-fos/genetics/metabolism
Male
Transcriptome
Gene Regulatory Networks
Molecular Docking Simulation

@article {pmid41607252,
year = {2026},
author = {Huang, R and Wu, Y and Liu, X and Zou, L and Li, J and He, J and Yang, L and Yang, X},
title = {Sulfur-Fumigation Engineered Ceria Nanoparticles With Augmented Oxygen Vacancies for Enhanced Therapy of Drug-Induced Liver Injury.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e13609},
doi = {10.1002/smll.202513609},
pmid = {41607252},
issn = {1613-6829},
support = {CSTB2024NSCQ-MSX0554//Natural Science Foundation of Chongqing/ ; },
abstract = {The excessive generation of reactive oxygen species (ROS) and its synergistic interplay with inflammation and apoptosis play a critical role in the progression of drug-induced liver injury (DILI). Ceria nanoparticles are potential DILI therapy candidates due to their self-renewable ROS scavenging activity. However, the clinical translation of ceria nanoparticles for DILI therapy is challenged by enhanced ROS scavenging activity and prolonged hepatic retention. Herein, the sulfur-fumigation approach is used to modulate the ROS scavenging activity of ceria nanoparticles through the surface microstructure reconfiguration mechanism. The sulfur-fumigation induces nanoparticle contraction and crystalline fusion. Crucially, sulfur-fumigation decreases (111) plane exposure but increases (200) and (220) plane exposure. These changes cause the generation of abundant oxygen vacancies, which significantly enhances the ROS scavenging activity of ceria nanoparticles, even when the surface area is decreased. Together with an appropriate hydrodynamic diameter (135.9 nm) for liver targeting, the sulfur-fumigated ceria nanoparticles can easily accumulate in the liver and alleviate ROS, inflammation, and apoptosis in DILI mice. Compared to the clinical standard N-acetylcysteine (NAC), the sulfur-fumigated ceria nanoparticles show better therapeutic efficacy across most of the detected parameters. These findings suggest that sulfur-fumigation is a potent surface reconfiguration strategy to engineer highly active ceria nanoparticles for DILI therapy.},
}

@article {pmid41606955,
year = {2026},
author = {Wang, C and Zhang, H and Guan, C and Li, Y and Yang, S and Huang, L},
title = {Glutamine transporter SLC1A5 inhibits autophagy-mediated CD276 degradation to promote esophageal cancer progression.},
journal = {Cancer biology & therapy},
volume = {27},
number = {1},
pages = {2621606},
doi = {10.1080/15384047.2026.2621606},
pmid = {41606955},
issn = {1555-8576},
mesh = {Humans ; Animals ; *Amino Acid Transport System ASC/metabolism/genetics/antagonists & inhibitors ; Mice ; *Esophageal Neoplasms/pathology/metabolism/genetics ; *Autophagy ; *Minor Histocompatibility Antigens/metabolism/genetics ; Cell Proliferation ; Disease Progression ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Female ; Xenograft Model Antitumor Assays ; Male ; Glutamine/metabolism ; Mice, SCID ; Mice, Inbred NOD ; Proteolysis ; },
abstract = {BACKGROUND: CD276/B7-H3 is an immune checkpoint molecule often overexpressed in cancers, representing a potential therapeutic target. The underlying mechanisms for CD276 upregulation remain unclear. This study investigates how glutamine metabolism affects CD276 protein stability and esophageal squamous cell carcinoma (ESCC) progression.

METHODS: CD276 and SLC1A5 expression were analyzed in 90 ESCC clinical tissues and TCGA/GEO datasets. CCK-8, colony formation, wound healing and transwell assays were performed in KYSE150 and KYSE450 cells. Autophagy was quantified by immunofluorescence and western blot. Mitochondrial reactive oxygen species (ROS) levels measured by flow cytometry. Rescue experiments used N-acetylcysteine (NAC) and chloroquine (CQ). Finally, antitumor effects of SLC1A5 inhibitor V9302 in the presence or absence of CD276 were evaluated in NOD/SCID mice (n = 5 per group) bearing KYSE150 xenografts.

RESULTS: CD276 and SLC1A5 upregulated in ESCC tissues (P < 0.05). CD276 overexpression enhanced ESCC cell proliferation and migration by 42.3% and 58.7%, respectively (P < 0.01). CQ but not MG-132 increased CD276 expression in ESCC cells. SLC1A5 stabilized CD276 protein without altering CD276 mRNA levels, by suppressing ROS-dependent autophagic degradation. NAC reversed ROS-induced CD276 degradation, while CQ abrogated CD276 downregulation upon glutamine metabolism inhibition. Inhibiting glutamine metabolism could reverse ESCC cell proliferation induced by CD276 overexpression. Moreover, combination of V9302 and CD276 knockout significantly reduced KYSE150 cell-derived xenograft tumor volume by 65.2% (95% CI 58.3-72.1%, P < 0.001) in NOD/SCID mice, without affecting mouse body weight (P > 0.05).

CONCLUSION: SLC1A5 enhances CD276 stability by suppressing ROS-autophagy signaling, promoting ESCC progression. Targeting glutamine metabolism to enhance CD276 degradation might be a novel therapeutic strategy for ESCC.},
}

Humans
Animals
*Amino Acid Transport System ASC/metabolism/genetics/antagonists & inhibitors
Mice
*Esophageal Neoplasms/pathology/metabolism/genetics
*Autophagy
*Minor Histocompatibility Antigens/metabolism/genetics
Cell Proliferation
Disease Progression
Reactive Oxygen Species/metabolism
Cell Line, Tumor
Female
Xenograft Model Antitumor Assays
Male
Glutamine/metabolism
Mice, SCID
Mice, Inbred NOD
Proteolysis

@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