Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Pharmacological Modulation of Catecholaminergic Brain Injury by Dapagliflozin and Its Nanovesicular Formulation in an Isoproterenol Model","authors":"Faisal Ashraf Bhat,&nbsp;Syed Ehtaishamul Haque,&nbsp;Mohammed Aqil,&nbsp;Mohd Akhtar,&nbsp;Abul Kalam Najmi","doi":"10.1002/jbt.71134","DOIUrl":"https://doi.org/10.1002/jbt.71134","url":null,"abstract":"<p>Sustained β-adrenergic stimulation represents a pharmacologically relevant stressor capable of inducing systemic oxidative and inflammatory injury that extends to the central nervous system. Isoproterenol (ISO), a synthetic catecholamine, is widely used to model catecholaminergic injury in experimental settings. Dapagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor, exhibits pleiotropic antioxidant and anti-inflammatory properties; however, its effects on catecholamine-induced brain injury remain poorly defined. In the present study, we investigated the pharmacological effects of dapagliflozin and a bile salt–stabilized dapagliflozin-loaded nanovesicular formulation in an ISO-induced model of catecholaminergic brain injury in rats. ISO administration resulted in marked oxidative imbalance, neuroinflammatory activation, behavioral dysfunction, and structural alterations in hippocampal and cortical regions. These changes were accompanied by reduced expression of stress-responsive and neurotrophic proteins, including SIRT6, TRAP1, and BDNF, along with enhanced astroglial activation as indicated by increased GFAP immunoreactivity. Treatment with dapagliflozin attenuated these molecular, cellular, and functional alterations, while the nanovesicular formulation produced a more pronounced improvement of redox balance, suppression of inflammatory responses, normalization of protein expression, and preservation of neuronal architecture and behavior. Collectively, these findings demonstrate that dapagliflozin mitigates catecholaminergic brain injury through attenuation of oxidative and inflammatory stress, with enhanced efficacy achieved via formulation-assisted drug delivery, without implying a distinct pharmacodynamic mechanism.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01537 Regulates Malignant Phenotypes and Predicts Prognosis in Breast Cancer, and Its Bioinformatics Analysis","authors":"Yuetong Guo,&nbsp;Libo Shi","doi":"10.1002/jbt.71123","DOIUrl":"https://doi.org/10.1002/jbt.71123","url":null,"abstract":"<p>Breast cancer is a highly heterogeneous malignancy and constitutes one of the leading health threats to women globally. This study aimed to investigate the expression profile, clinical relevance, and molecular mechanisms of LINC01537 in breast cancer. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of LINC01537, miR-138-5p, and EZH2 in breast cancer tissues and cells. The Kaplan-Meier method was used for survival analysis, and forest plots were constructed to evaluate the prognostic significance of LINC01537. To explore the role of LINC01537 in BT549 and SK-BR-3 cells proliferation, apoptosis, migration, and invasion, LINC01537 was knocked down in BT549 and SK-BR-3 cells, followed by CCK-8, flow cytometry, and Transwell assays. A potential competing endogenous RNA (ceRNA) regulatory network was investigated through bioinformatics analysis, dual-luciferase reporter assays, and correlation analyses. Rescue experiments were further performed to confirm that LINC01537 modulates breast cancer progression via the miR-138-5p/EZH2 axis. LINC01537 was significantly upregulated in breast cancer tissues and cell lines compared to normal controls. High LINC01537 expression was associated with poor survival outcomes in patients. Knockdown of LINC01537 markedly suppressed proliferation, migration, and invasion, while promoting apoptosis in BT549 and SK-BR-3 cells. Mechanically, LINC01537 functioned as a ceRNA by sponging miR-138-5p, thereby abrogating its inhibitory effect on the target gene EZH2. Rescue experiments suggested that the inhibition of the malignant phenotypes of BT549 and SK-BR-3 cells caused by LINC01537 knockdown was rescued by miR-138-5p inhibition. The LINC01537/miR-138-5p/EZH2 ceRNA axis is involved in the progression of TNBC and HER2-positive breast cancer subtypes. In vitro data indicates that LINC01537 is a potential therapeutic candidate for TNBC and HER2-positive breast cancer, while further in vivo animal validation is required to support its translational application.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin Attenuates Vincristine-Induced Nephrotoxicity via Nrf2/HO-1 and PI3K/Akt/mTOR Signaling","authors":"Aydin Genc,&nbsp;Bayram Akoglan,&nbsp;Emre Sahin,&nbsp;Eren Cankaya","doi":"10.1002/jbt.71136","DOIUrl":"https://doi.org/10.1002/jbt.71136","url":null,"abstract":"<p>Vincristine (VIN) is a widely used chemotherapeutic agent whose therapeutic application is substantially constrained by concentration-dependent toxicities, including nephrotoxicity. This study aimed to characterize the renoprotective capacity of hesperidin (HES) in a VIN-induced nephrotoxicity model and to delineate the mechanisms underlying its protective action. Twenty-eight female Wistar albino rats were divided into four groups: control, HES (200 mg/kg), VIN (0.17 mg/kg), and VIN (0.17 mg/kg) + HES (200 mg/kg), with all treatments administered for 7 consecutive days. Renal function markers, oxidative stress parameters, apoptosis- and autophagy-related gene expression, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling components, and histopathological alterations were evaluated. VIN administration significantly increased serum urea and creatinine levels, lipid peroxidation, and oxidative DNA damage, while reducing antioxidant defenses (<i>p</i> &lt; 0.05). VIN also induced marked apoptosis, evidenced by increased tumor protein p53 (p53), Bcl-2-associated X protein (Bax), Caspase-3, and C/EBP homologous protein (CHOP) expression and decreased B-cell lymphoma 2 (Bcl-2) levels, together with enhanced autophagy and suppression of PI3K/Akt/mTOR signaling (<i>p</i> &lt; 0.05). These molecular changes were accompanied by severe renal histopathological damage (<i>p</i> &lt; 0.05). HES supplementation significantly attenuated these effects by restoring antioxidant capacity, reducing inflammatory cytokines, suppressing apoptosis, modulating autophagy-related gene expression, and partially restoring PI3K/Akt/mTOR signaling (<i>p</i> &lt; 0.05). Histopathological findings further confirmed the protective effect of HES against VIN-induced renal injury (<i>p</i> &lt; 0.05). In conclusion, HES exerts renoprotective effects against VIN-induced nephrotoxicity by modulating interconnected oxidative stress, inflammation, apoptosis, autophagy, and PI3K/Akt/mTOR signaling pathways, suggesting its potential as a multi-target agent for preventing chemotherapy-associated renal injury in this experimental model.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01352 Inhibits Lung Adenocarcinoma Progression by Modulating the miR-425-5p/SRSF11 Pathway","authors":"Xiaoxiao Ma,&nbsp;Ling Liu,&nbsp;Fang Fang","doi":"10.1002/jbt.71109","DOIUrl":"10.1002/jbt.71109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Lung adenocarcinoma (LUAD), as the most common subtype of non-samll cell lung cancer, is highly malignant and associated with a poor overall prognosis for patients, making it imperative to further investigate its molecular mechanisms of pathogenesis. This study aims to clarify the role of LINC01352 in the malignant progression of lung adenocarcinoma (LUAD). LINC01352 expression in LUAD versus normal tissue was analyzed using StarBase and GEPIA databases. RT-qPCR was employed to explore the levels of LINC01352, miR-425-5p, and SRSF11 in102 clinically collected LUAD tissue samples. Cell proliferation was assessed using the CCK-8 assay, while cell migration and invasion capabilities were examined via Transwell experiments. DLR and RIP experiments were performed to validate the target relationships between LINC01352 and miR-425-5p, as well as SRSF11 and miR-425-5p. The level of LINC01352 decreased in LUAD, and enhancing LINC01352 inhibited the malignant phenotype of LUAD cells. LINC01352 binds to miR-425-5p. Increasing miR-425-5p expression offset the inhibitory impacts of LINC01352 overexpression on the malignant behavior of LUAD cells. Furthermore, SRSF11 is a target of miR-425-5p, and its expression in LUAD tissues showed a significant inverse relationship with miR-425-5p. LINC01352 exerts tumor-suppressive function in LUAD through the miR-425-5p/SRSF11 axis, thereby inhibiting malignant progression of LUAD. This study indicates that targeting the LINC01352/miR-425-5p/SRSF11 pathway may represent a promising therapeutic strategy for LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Titanium Dioxide Exacerbates Calcium Phosphate and Urate-Induced Oxidative Stress, Injury and Inflammatory Response in Human Kidney-2 Cells","authors":"Samshritha R. Bikki,&nbsp;Aditi Mohapatra,&nbsp;Samuel Shin,&nbsp;Bidhan C. Bandyopadhyay","doi":"10.1002/jbt.71133","DOIUrl":"10.1002/jbt.71133","url":null,"abstract":"<p>The widespread use of titanium dioxide (TiO₂) nanoparticles (TNPs) in everyday products (ex; cosmetics, food additives) has growing concerns about their harmful effects on humans due to unavoidable exposure. We recently found that TNPs could stabilize both calcium phosphate (CaP) and uric acid (UA) crystals, implicating kidney stone formation. However, the impact of TNPs on the kidney, specifically on kidney tubular cells is unknown. Therefore, we investigated the effect of TiO₂ alone or in combination with UA/CaP microcrystals on Ca²⁺ dynamics by measuring Ca²⁺ transients, reactive oxygen species (ROS) production by H₂DCFDA staining and H₂O₂ release, oxidative stress and inflammatory response by gene expression analysis, cell death by DAPI and Annexin V/propidium iodide (PI) staining and cytotoxicity by lactate dehydrogenase (LDH) release in human kidney (HK-2) tubular cell line. The internalization of CaP/UA crystals with TiO₂ in HK-2 cells resulted in an enhanced store-operated Ca²⁺ entry (SOCE), which was blocked by Pyr6 (SOCE inhibitor). Indeed, the combination of CaP/UA crystals with TiO₂ -internalized HK-2 cells showed a pronounced increase in ROS production and LDH release compared to CaP and/or UA crystals groups, which were reduced by SOCE inhibition. Analyses of nuclear morphology via DAPI staining indicated a greater cell injury/death response in the presence of TiO₂ with CaP/UA crystals. Annexin V/PI staining revealed a greater percentage of apoptosis/necrosis after internalization of CaP/UA with TiO₂, which was decreased upon preapplication of Pyr6. Gene expression analyses show that internalization of CaP/UA+TiO₂ crystals evoked upregulation of oxidative stress (NOX4), inflammatory (MCP-1, TNF-α), fibrotic (FN-1) and apoptotic (BCL2) genes. Taken together, TNPs, when combined with CaP/UA, became the activator of SOCE to promote oxidative stress, inflammation, tubular injury and cytotoxicity, underscoring their implications in crystal-induced nephropathy and stone formation.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-Carcinogenic Implications of Folic Acid Supplementation During Chemically Induced Cutaneous Squamous Cell Carcinoma in Mice","authors":"Neha Arora Chugh,&nbsp;Shashi Bala,&nbsp;Tuhin Mallick,&nbsp;Ashwani Koul","doi":"10.1002/jbt.71117","DOIUrl":"10.1002/jbt.71117","url":null,"abstract":"<p>In light of the increasing exposure to folate and its unresolved relationship with skin cancer, experimental studies are warranted to better understand and define its role in skin carcinogenesis. The present study evaluated the effects of folic acid supplementation on cutaneous squamous cell carcinoma (cSCC) in mice and explored the underlying mechanisms. A two-stage skin carcinogenesis model was employed using 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as initiator and tumor promoter respectively. LACA mice were orally supplemented with folic acid (FA) at doses of 1 or 2 mg/kg body weight and divided into six groups: control, DMBA/TPA, FA1(1 mg/kg) + DMBA/TPA, FA2(2 mg/kg) + DMBA/TPA, FA1 and FA2 groups. Supplementation began 4 weeks prior to tumor induction and continued for twenty weeks. Histopathological analysis confirmed cSCC development. During the early stages, papilloma incidence was higher in FA1 + DMBA/TPA and FA2 + DMBA/TPA groups in comparison to DMBA/TPA group. However, by the end of the treatment period, lesion incidence reached 100% in all groups, with a greater total lesion count and lesion burden observed in the supplemented groups its indicating pro-carcinogenic effects. Enhanced cellular proliferation in these groups was evident from histomorphometric assessments and increased expression of proliferating cell nuclear antigen and folate transporters. Increase in tumorigenesis was also associated with enhanced activity of serum lactate dehydrogenase, oxidative DNA damage and inhibition in expression of MGMT gene. However, no noteworthy difference was observed between two levels of supplementation. These findings suggest that folic acid supplementation may promote skin tumorigenesis through increased proliferation, enhanced DNA damage, and impaired DNA repair mechanisms.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT3-Dependent Actions of Berberine: From Molecular Therapies to Toxicity","authors":"Dareuosh Shackebaei,&nbsp;Seyed Shahram Miraghaee,&nbsp;Faegheh Farhadi,&nbsp;Abolfazl Akbarzadeh,&nbsp;Fatemeh Yarmohammadi","doi":"10.1002/jbt.71126","DOIUrl":"10.1002/jbt.71126","url":null,"abstract":"<p>Berberine, an alkaloid with broad bioactive properties, exerts its pleiotropic effects by modulating SIRT3, a mitochondrial NAD⁺-dependent deacetylase. This review examines the dual role of SIRT3 as a target of berberine in the management of various disorders while also addressing its associated toxicological profiles. The antihyperglycemic effects of berberine are mediated through SIRT3 inhibition, which promotes hyperacetylation of complex I subunits, degradation of MPC1, an increased AMP/ATP ratio, AMPK activation, and suppression of PEPCK1, collectively resulting in the inhibition of gluconeogenesis. In contrast, the hypolipidemic, cardioprotective, and hepatoprotective effects of berberine are associated with SIRT3 activation, which facilitating adipose tissue remodeling, enhancing β-oxidation in NAFLD, promoting lipophagy in diabetic cardiomyopathy, and mitigates doxorubicin-induced cardiotoxicity. Furthermore, berberine exhibits antitumor duality, exerting contrasting effects in colorectal cancer and hepatoma models, and demonstrates versatile mitochondrial metabolic reprogramming in polycystic ovarian syndrome. Notably, ocular toxicity associated with berberine has been linked to SIRT3 inhibition in photoreceptors cells. Overall, the therapeutic versatility of berberine is fundamentally associated with its context-dependent modulation of SIRT3, positioning it as a promising mitochondrial epigenetics modulator for conditions such as metabolic syndrome, NAFLD, and DCM. However, its therapeutic application must be carefully balanced against organ-specific toxicity risks.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentially Toxic Elements and Male Reproductive Toxicity: Mechanisms, Implications, and Protective Strategies: A Narrative Review","authors":"Sakshi Yadav,&nbsp;Placheril J John","doi":"10.1002/jbt.71128","DOIUrl":"10.1002/jbt.71128","url":null,"abstract":"<p>The male reproductive system is highly vulnerable to environmental toxicants, particularly potentially toxic elements (PTEs), which represent a growing public health concern worldwide. Increasing evidence indicates that these elements impair male reproductive function through interconnected mechanisms including oxidative stress, endocrine disruption, inflammation, apoptosis, and DNA damage, resulting in impaired spermatogenesis and infertility. This review summarizes the current understanding of the major PTEs associated with male reproductive toxicity and highlights the underlying cellular and molecular mechanisms responsible for testicular injury. In addition, it discusses emerging protective and therapeutic strategies, including antioxidants, phytochemicals, nutraceuticals, chelating agents and lifestyle-based interventions that have shown potential in mitigating PTE-induced reproductive damage. A comprehensive understanding of these mechanisms and protective approaches may facilitate the development of effective preventive and therapeutic strategies to preserve male reproductive health in populations exposed to PTEs.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology-Based Prediction and In Vivo Validation of Fumonisin B1-Induced Liver Injury and Early Fibrosis","authors":"Na Li,&nbsp;Wen Sun,&nbsp;Xuehui Liu,&nbsp;Xinyu Liu,&nbsp;Yunhan Xie,&nbsp;Hao Xu,&nbsp;Linlin Xu,&nbsp;Jia Zang,&nbsp;Leilei Zhang,&nbsp;Liang Wu,&nbsp;Keke Shao","doi":"10.1002/jbt.71129","DOIUrl":"10.1002/jbt.71129","url":null,"abstract":"<p>Fumonisin B1 (FB1) is a widespread mycotoxin contaminating food and feed, exhibiting severe hepatotoxicity. This study aimed to systematically investigate the underlying molecular mechanisms of FB1-induced liver injury and early liver fibrosis by combining network pharmacology with an in vivo animal model. First, network pharmacology and molecular docking were utilized to screen the core targets and key signaling pathways of FB1-induced hepatotoxicity. Subsequently, an in vivo C57BL/6 mouse model was established via intragastric administration of FB1 (5 mg/kg/day for 28 days). Serum levels of liver function and fibrosis markers (ALT, AST, HA, LN, PCIII, CIV) were measured. Histopathological changes and collagen deposition in liver tissues were evaluated using HE and Masson's trichrome staining. The relative mRNA expression of inflammation- (<i>TNF-α</i>, <i>IL-1β</i>, <i>IL-6</i>) and fibrosis-related core genes (<i>TGF-β1</i>, <i>α-SMA</i>, <i>COL1A1</i>) was quantified by qPCR. Network pharmacology predicted that inflammatory responses and fibrosis-related pathways are central to FB1 hepatotoxicity. In vivo experiments confirmed that FB1 exposure significantly elevated serum ALT and AST levels, as well as the four indices of liver fibrosis (<i>p</i> &lt; 0.001). Histopathology revealed severe hepatocyte necrosis, inflammatory cell infiltration, and massive deposition of blue-stained collagen fibers. Furthermore, qPCR results demonstrated that FB1 significantly upregulated the expression of pro-inflammatory cytokines, strongly activated the TGF-β1 signaling pathway, and promoted the high expression of the hepatic stellate cell (HSC) activation marker (α-SMA) and extracellular matrix (COL1A1). In conclusion, FB1 drives the pathogenesis of early liver fibrosis by inducing sustained hepatic inflammation and activating the TGF-β1 signaling pathway, which promotes HSC activation and excessive extracellular matrix deposition. This study provides a vital theoretical basis for elucidating the target-organ toxicity mechanisms of mycotoxins and identifying potential interventions.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Improves Silica Induced Lung Fibrosis by Targeting TLR4-NLRP3 Inflammasome and TGF-β Inhibition in Mice Model","authors":"Sneha Kumari,&nbsp;Payal Singh,&nbsp;D. Dash,&nbsp;Rashmi Singh","doi":"10.1002/jbt.71116","DOIUrl":"10.1002/jbt.71116","url":null,"abstract":"<p>Silicosis, a progressive occupational lung disease, caused by inhalation of crystalline silica particles, leads to chronic inflammation and pulmonary fibrosis. Increasing evidence suggests that activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome plays a crucial role in silica-induced lung injury. This study was undertaken to investigate protective effects of curcumin against silica-induced pulmonary inflammation and fibrosis where its efficacy was compared with dexamethasone. For inducing silicosis, mice experienced silica exposure for 35 days, followed by intranasal curcumin administration. The study evaluated inflammatory responses, macrophage polarization, fibrotic alterations, and the expression of key mediators, including TLR4, NF-κB, NLRP3, ASC, caspase-1, IL-1β, TNF-α, IL-6, IL-18, TGF-β, and FN-1. Curcumin significantly reduced inflammatory cytokine expression, suppressed NLRP3 inflammasome activation, and promoted macrophage polarization toward the anti-inflammatory M2 phenotype. In addition, curcumin attenuated fibrosis by decreasing TGF-β and FN-1 expression, collagen deposition, and extracellular matrix accumulation. Histopathological findings confirmed reduced alveolar damage, silicotic nodules, goblet cell hyperplasia, mucus hypersecretion, and pulmonary fibrosis in curcumin treatment groups. This study established alleviation of silica-induced pulmonary inflammation and fibrosis by inhibiting TLR4/NF-κB and TGF-β signaling, suppressing NLRP3 inflammasome activation. It highlights the potential clinical significance of curcumin as a promising therapeutic agent in the management of silicosis and progressive lung fibrosis.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}