Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Falcarindiol Suppresses Malignant Progression and Induces Ferroptosis in Non-Small Cell Lung Cancer by Regulating JAK/STAT3 Axis","authors":"Zhenliang Shi,&nbsp;Yimeng Shen,&nbsp;Xin Liu,&nbsp;Shizhao Cheng","doi":"10.1002/jbt.70486","DOIUrl":"https://doi.org/10.1002/jbt.70486","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Non-small cell lung cancer (NSCLC) is the most prevalent human malignancy, characterized by high morbidity and mortality rates. Falcarindiol (FAD) has been validated to provide remission in multiple human tumors. However, the function of FAD in NSCLC is unclear. Hence, this research aimed to elucidate the role and potential mechanism of FAD in NSCLC. The toxic effect of FAD on BEAS-2B cells was investigated by cell counting kit-8 (CCK-8) assay. Also, the impact of FAD on NSCLC in vitro models was examined using CCK-8 analysis, western blot analysis, Transwell assay, Fe2+ level determination, immunofluorescence, and transmission electron microscope assays. Furthermore, the mechanism of FAD in NSCLC was assessed with western blot analysis, CCK-8 analysis, Transwell, and Fe2+ level determination. Additionally, the roles of FAD in NSCLC in vivo models were determined using a tumor xenograft model, immunohistochemistry assay, and western blot analysis. FAD concentrations below 160 µM exhibited no significant cytotoxicity toward BEAS-2B cells. FAD reduced NSCLC cell proliferation and invasion functionally, decreased PCNA, ki-67, and N-cadherin protein levels, while FAD increased E-cadherin protein levels. Meanwhile, FAD induced NSCLC cell ferroptosis by increasing Fe2+ and reactive oxygen species levels and decreasing GPX4 and xCT protein levels in NSCLC cells. Also, FAD induced mitochondrial fragmentation in NSCLC. Mechanically, FAD attenuated NSCLC cell proliferation, invasion, and enhanced cell ferroptosis, while RO8191 (activator of JAK/STAT3) reversed these effects. Furthermore, FAD repressed NSCLC cell proliferation in vivo by reducing tumor volume and tumor weight, decreasing ki-67, N-cadherin, GPX4, xCT, p-JAK1, p-JAK2, and p-STAT3 protein levels, and increasing E-cadherin protein levels. FAD attenuated NSCLC proliferation, invasion, and enhanced cell ferroptosis through the inhibition of the JAK/STAT3 signaling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZnO Nanoparticles Interacts With Unique Serum Proteins and Induce Stress Signaling During Hepatoxicity - A Proteomics and Molecular Pathways Study","authors":"Gobichettipalayam Balasubramaniam Maadurshni,&nbsp;Balamurali Mahalakshmi,&nbsp;Manikandan Nagarajan,&nbsp;Panchatcharam Swathika,&nbsp;Ganesan Harinikkamatchi,&nbsp;Anand Kumar Anusha,&nbsp;Jeganathan Manivannan","doi":"10.1002/jbt.70480","DOIUrl":"https://doi.org/10.1002/jbt.70480","url":null,"abstract":"<div>\u0000 \u0000 <p>The release of synthesized zinc oxide nanoparticles (ZnO-NPs) into the environment and consequent human exposure risk brought enormous attention in recent years. In recent decades, a range of toxicological effects were highlighted on hepatotoxic risk during ZnO-NPs exposure without precise mechanistic verification. The current study employed proteomic profiling (LC-MS/MS) to unveil the interaction of ZnO-NPs with human serum proteins (protein corona) and its relevant hepatotoxic mechanisms. Further, chicken embryo model and primary hepatocyte cell culture protocols (fluorescence assays and confocal imaging) were used to explore developmental hepatotoxicity and cellular stress responses respectively. Further, mediatory role of redox enzymes by siRNA experiments and synergistic effect of ZnO-NPs on cellular impact of disease risk factors were also explored. The protein corona composition provides plausible mechanistic insights on liver transport and associated hepatotoxic pathways (Reactome and KEGG). Moreover, the detrimental impact on developing embryonic liver, RBC and tissue redox enzymes were also observed. The expression studies (RT-qPCR and western blot) indicate an elevated response of oxidative stress associated genes (HO-1 and NQO1) and cellular stress signaling factors (HSP27, JNK, P53, c-JUN, MAPK). The current study revealed a stimulatory effect of ZnO-NPs on oxidative stress, cellular calcium overload and autophagy. Further, the mediatory effect of NOX2 and XO on ZnO-NPs induced cytotoxicity and superoxide generation was validated. Notably, ZnO-NPs exposure increased the adverse effect of inflammatory and metabolic risk factors in hepatocytes. Overall results highlight novel mechanistic insights on hepatotoxic effect of ZnO-NPs towards a precise assessment on the magnitude of human exposure risk.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Oxidative Stress With Combination Treatment of Alpha-Lipoic Acid and Antiseizure Drugs in Rodent Model: A Systematic Review","authors":"Muskan Jalan,&nbsp;Shalini Singh,&nbsp;Malhar Desai,&nbsp;Anuradha Sharma,&nbsp;Sunik Malik,&nbsp;Anju Singh,&nbsp;Ritushree Kukreti,&nbsp;Shrikant Kukreti,&nbsp;Gurpreet Kaur Grewal","doi":"10.1002/jbt.70488","DOIUrl":"https://doi.org/10.1002/jbt.70488","url":null,"abstract":"<div>\u0000 \u0000 <p>Epilepsy is a chronic neurological disease marked by repeated seizures due to excessive neuronal activity, frequently linked to oxidative stress. Treatment in epilepsy involves chronic use of antiseizure drugs (ASDs) which further exacerbates oxidative stress. Given its role in epilepsy, oxidative stress has been a target for therapeutic intervention, with antioxidants being explored as potential agents to mitigate oxidative damage. This systematic review investigates studies which have used alpha lipoic acid (ALA) in conjunction with ASDs in rodents, and focuses on its antioxidant properties on oxidative stress, biochemical activity, molecular activity and behavioral outcomes. Following PRISMA guidelines, a comprehensive literature search across Google Scholar, ScienceDirect, Springer Link, and PubMed databases from 2020 to 2025 yielded 4622 studies, of which seven met the inclusion criteria. The results reveal that ALA, either alone or in combination with ASD, significantly mitigates oxidative stress by reducing malondialdehyde levels and enhancing the role of key antioxidants such as catalase, glutathione, superoxide-dismutase, etc. Additionally, ALA alleviates behavioral deficits and exhibits neuroprotective, hepato-protective, and anti-inflammatory effects. Furthermore, ALA modulates molecular markers by upregulating Nrf-2 and SIRT1 pathways while downregulating TNF-α and caspase 3, thereby reducing apoptosis and inflammation. Although promising, the findings are constrained by limited sample sizes, brief study periods, and a lack of comprehensive investigations on dose–response relationships and systemic effects. Most of the studies focus on limited biochemical and molecular markers, overlooking comprehensive evaluations of systemic and behavioral outcomes. This review highlights the potential of ALA as an adjunct therapy for epilepsy and emphasizes the need for more robust preclinical studies to confirm its efficacy and to fill the lacunas for advancing the therapeutic potential of ALA in epilepsy management.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-Conditioning and Post-Conditioning of Ischemia Reperfused Rat Hearts: Sustained Protection in Normal Hearts; Ineffective in PM2.5 Exposed Hearts Due to Toxicity","authors":"Bhavana Sivakumar,&nbsp;Gino A. Kurian","doi":"10.1002/jbt.70471","DOIUrl":"https://doi.org/10.1002/jbt.70471","url":null,"abstract":"<div>\u0000 \u0000 <p>The present study addresses the toxicological impact of Particulate matter (PM_2.5) exposure on the pharmacological efficacy of ischemia preconditioning (IPC) and postconditioning (POC) against ischemia-reperfusion (IR) injury. The primary motivation for this study is the gap in knowledge regarding the effectiveness of IPC and POC in PM_2.5 modified hearts. With the increasing prevalence of cardiac procedures involving IR and PM_2.5 toxicity, there is a growing need to understand their interaction. Female Wistar rats were subjected to PM_2.5 exposure for 3 h daily over a period of 21 days. Subsequently, their hearts were excised and mounted on a Langendorff perfusion apparatus. Three cycles of IPC and POC were applied, followed by the IR protocol. In contrast to hearts under normal conditions, neither IPC nor POC could reduce cardiac injury (infarct size, apoptosis, and inflammation) or enhance cardiac function in PM_2.5-exposed hearts subjected to IR. The underlying reason for this ineffectiveness was identified as the inability to improve mitochondrial bioenergetic function and the expression of the declined master regulator gene Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Additionally, the compromised mitochondrial quality control genes resulting from PM_2.5 exposure could not be restored to their normal levels by these conventional strategies. Furthermore, the crucial pro-survival signaling pathways like phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) could not be reactivated by these strategies in PM_2.5-exposed hearts undergoing IR, consequently preventing the restoration of cardioprotection. From the above results, we deduce that the therapeutic benefits of mechanical conditioning techniques such as IPC and POC were compromised in hearts exposed to PM_2.5, primarily attributed to PM_2.5 induced mitochondrial dysfunction.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide Attenuates Traumatic Heterotopic Ossification via Modulation of Inflammatory and Differentiation Pathways: Implications for Biochemical Toxicology","authors":"Zuo-Hua Li,&nbsp;Zong-Huan Li,&nbsp;Zheng Wang,&nbsp;Xiang Jiang,&nbsp;Ai-Xi Yu","doi":"10.1002/jbt.70482","DOIUrl":"https://doi.org/10.1002/jbt.70482","url":null,"abstract":"<p>Traumatic heterotopic ossification (THO) is a pathological process characterized by ectopic bone formation in soft tissues following trauma or surgical interventions, leading to pain, swelling, and restricted mobility. Current therapeutic strategies remain limited, with surgical excision often associated with recurrence and complications. Triptolide (TP), a diterpenoid triepoxide derived from <i>Tripterygium wilfordii</i>, has potent anti-inflammatory and immunomodulatory effects, making it a promising candidate for THO treatment. This study explored the molecular mechanisms underlying the therapeutic potential of TP in THO, focusing on its effects on inflammatory and differentiation pathways. Using in vitro models with mouse tendon stem/progenitor cells (TSPCs) and RAW264.7 macrophages, as well as an in vivo mouse model of THO, we demonstrated that TP significantly inhibits key signalling pathways involved in THO pathogenesis, including the NF-κB, TGF-β-Smad, and Notch pathways. TP reduces the levels of Pro-inflammatory cytokines (IL-1β and TNF-α) and suppresses the osteogenic and chondrogenic differentiation of mesenchymal stem cells, which are critical processes in THO development. Moreover, compared with the commonly used anti-inflammatory drug indomethacin, TP markedly reduces ectopic bone formation in vivo, exhibiting superior efficacy. These findings highlight the potential of TP as a novel therapeutic agent for THO, providing new insights into its biochemical and molecular effects relevant to toxicology and inflammation regulation.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927232","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":"Endoplasmic Reticulum Stress Inhibition Alleviates Tourniquet-Induced Limb Ischemia-Reperfusion Injury","authors":"Zhongyang Sun,&nbsp;Keran Li,&nbsp;Jianlin Wang,&nbsp;Lei Zhao,&nbsp;Huanbo Wang,&nbsp;Qi Wu,&nbsp;Zhengrong Ren,&nbsp;Baosheng Guo,&nbsp;Xin Yu,&nbsp;Ying Li","doi":"10.1002/jbt.70476","DOIUrl":"https://doi.org/10.1002/jbt.70476","url":null,"abstract":"<div>\u0000 \u0000 <p>Tourniquet-induced limb ischemia-reperfusion (I/R) injury can cause significant skeletal muscle damage, yet the role of endoplasmic reticulum (ER) stress in this context remains poorly understood. In this study, a mouse model of hindlimb I/R injury was established by applying an orthodontic rubber band for 4 h, followed by 24 h of reperfusion. To investigate the involvement of ER stress and the therapeutic potential of sodium 4-phenylbutyric acid (4-PBA), a clinically available ER stress inhibitor, mice were pretreated with 4-PBA (40 or 100 mg/kg, intraperitoneally) before ischemia. ER stress activation and associated pathological responses were assessed using qRT-PCR, Western blot analysis, immunohistochemistry, histological staining, and transmission electron microscopy. Our results demonstrated that I/R induced pronounced ER stress activation in gastrocnemius muscle, which was closely associated with enhanced oxidative stress, inflammation, and apoptosis. Pretreatment with 4-PBA effectively attenuated ER stress and disrupted these detrimental feedback loops, thereby reducing tissue damage, preserving histological integrity, and improving microcirculation perfusion. Collectively, these findings underscore ER stress as a central mediator of limb I/R injury and support ER stress inhibition as a promising therapeutic strategy for attenuating skeletal muscle damage in tourniquet-associated clinical settings.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effects of Malvidin Hydrochloride Against Fipronil-Induced Oxidative Stress, Inflammation, and Apoptosis in Mice","authors":"Simge Garlı,&nbsp;Fatma Sahindokuyucu Kocasarı,&nbsp;Ozlem Ozmen","doi":"10.1002/jbt.70470","DOIUrl":"https://doi.org/10.1002/jbt.70470","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the protective effects of malvidin hydrochloride (MLV) against fipronil (FPN)-induced oxidative stress, inflammation, and apoptosis in mice. Control, FPN, and MLV groups received 0.9% NaCl with 0.1% DMSO, 5 mg/kg FPN, and 5 mg/kg MLV by gavage for 14 days. In the MLV + FPN group, MLV was administered 2 h before FPN for 14 days. Liver, kidney, and brain samples underwent biochemical, histopathological, and immunohistochemical analyses. FPN exposure led to significantly elevated serum AST, ALT, creatinine, and BUN levels compared to controls, while MLV + FPN co-treatment reduced these markers (<i>p</i> &lt; 0.05). The MLV + FPN group also showed reduced MDA, NF-κB2, 8-OHdG, TNF-α, IL-1β levels, and iNOS2 and COX-2 activities, with increased SOD, CAT, GPx1 enzyme activities, GSH, and Nrf2 levels (<i>p</i> &lt; 0.001). Tissue pathology was less severe in the MLV + FPN group, with reduced caspase-3, caspase-9, and Bax expressions and increased Bcl-2 expression (<i>p</i> &lt; 0.001). Results indicate that MLV offers antioxidant, anti-inflammatory, and antiapoptotic protection against FPN-induced liver, kidney, and brain damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Attenuates Cadmium-Induced Acute Lung Injury via Nrf2-Keap1 Pathway Activation","authors":"Zhenjie Gao,&nbsp;Dadi Shu,&nbsp;Yuchen Li,&nbsp;Zhaoming Chen,&nbsp;Yunzhi Sun,&nbsp;Qiongying Hu,&nbsp;Chuantao Zhang","doi":"10.1002/jbt.70463","DOIUrl":"https://doi.org/10.1002/jbt.70463","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium, a toxic heavy metals that would cause lung tissue damage and structural alterations via oxidative stress and inflammatory responses. This study was designed to investigate the protective function and its potential mechanism of quercetin against cadmium-induced acute lung injury. Rat and BEAS-2B cell models of CdCl₂-induced ALI were established, and the apoptotic and proliferative activities of tissue cells, inflammatory factors such as TNF-α, IL-6, and IL-1β, and the expression of key proteins in the Nrf2-Keap1 pathway, mitochondrial pathway, and mitochondrial membrane potential were examined using Immunohistochemistry, TUNEL, CCK8, ELISA, Western blot, and flow cytometry to evaluate the therapeutic effect of quercetin. Quercetin significantly alleviated CdCl₂-induced pulmonary edema, tissue damage and inflammatory response, and inhibited lung cell apoptosis in rats. It increased the expression of antioxidant enzyme genes, reduced ROS generation, restored Redox Equilibrium, and protected mitochondrial function by the Nrf2-Keap1 signaling pathway activation. In addition, quercetin also exhibited inhibitory effects on CdCl₂-induced apoptosis in BEAS-2B cells in vitro. Quercetin significantly attenuated cadmium-induced acute lung injury through antioxidant stress and protection of mitochondrial function, and has potential therapeutic value for acute lung injury.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of MicroRNA-4713-3p on Promoting Malignant Progression of Nasopharyngeal Carcinoma via Targeted Inhibition of EPHX3 to Activate Wnt/β-Catenin Signaling Pathway","authors":"Qichao Hong,&nbsp;Shuzhou Liu,&nbsp;Qimeng Zhang,&nbsp;Shun Ding,&nbsp;Chengliang Xing,&nbsp;Jingren Yan,&nbsp;Liuyang Zhang,&nbsp;Zhonglin Mu","doi":"10.1002/jbt.70450","DOIUrl":"https://doi.org/10.1002/jbt.70450","url":null,"abstract":"<div>\u0000 \u0000 <p>Nasopharyngeal carcinoma (NPC) represents a common malignancy in the head-and-neck region, and its development and prognosis can be influenced by multiple factors. Epoxide hydrolase 3 (EPHX3) is an enzyme that perform crucial roles in inflammation and tumors regulation. We aim to discuss the expression pattern and biological function of EPHX3 in NPC. The EPHX3 expression patterns in NPC tissues and cell lines were determined by the qRT-PCR technique. Correlations between EPHX3 expression and the clinical characteristics of NPC patients were subsequently assessed. Afterwards, the mechanism of miR-4713 targeting EPHX3 in NPC was validated either in vitro or in vivo. Gene set enrichment analysis and cell experiments were conducted to prove the impact of the EPHX3-regulated downstream Wnt/β-catenin pathway on the progression of NPC and epithelial-mesenchymal transition (EMT). EPHX3 mRNA expression was significantly downregulated in NPC tissues compared with adjacent normal tissues (<i>p</i> &lt; 0.01). Overexpression of miR-4713-3p markedly enhanced cell proliferation (<i>p</i> &lt; 0.05), migration, and invasion, while dual-luciferase and molecular docking confirmed that EPHX3 is a direct target of miR-4713-3p. Mechanistically, key components of the Wnt/β-catenin pathway, including β-catenin and c-Myc, were significantly upregulated following miR-4713-3p overexpression (<i>p</i> &lt; 0.01), whereas EPHX3 overexpression suppressed these changes and inhibited EMT. In vivo, miR-4713-3p knockdown suppressed tumor growth in xenograft models (<i>p</i> &lt; 0.05). Our study reveals the significance of EPHX3 in the development of NPC and offers a basis for the promise of EPHX3 as a possible therapeutic target.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Ethylhexyl Diphenyl Phosphate Inhibited C2C12 Myoblast Differentiation by Regulating ACTC1","authors":"Dai Lizhi,&nbsp;Yu Tong,&nbsp;Wang Jingxuan,&nbsp;Li Youchong,&nbsp;Cao Zheyuan,&nbsp;Xiao Jianhua","doi":"10.1002/jbt.70449","DOIUrl":"https://doi.org/10.1002/jbt.70449","url":null,"abstract":"<div>\u0000 \u0000 <p>2-ethylhexyl diphenyl phosphate (EHDPHP), a ubiquitous organic phosphorus flame retardant, is extensively employed in food packaging, flame retardancy applications, and other industrial processes as a crucial chemical. However, recent discoveries have underscored its diverse toxic effects, posing a severe potential threat to biological health. Skeletal muscle, vital for locomotion, relies heavily on proper differentiation during development and maintenance for strength and functionality. This study investigated the impact of EHDPHP on skeletal muscle differentiation by culturing C2C12 cells with varying concentrations of EHDPHP during induction of differentiation, as well as constructing a mouse muscle injury repair model through oral administration of 30 μg/kg EHDPHP for 7 weeks. Exposure to EHDPHP was found to impede skeletal muscle differentiation in mice. Utilizing techniques such as western blot analysis, RNA-seq, and qRT-PCR, our preliminary analysis revealed that low concentrations of EHDPHP inhibited the expression of ACTC1, subsequently suppressing MyoG and MYH2 expression levels, thereby hindering C2C12 myoblast differentiation. Furthermore, EHDPHP exposure disrupted the repair process of muscle injury in mice and compromised the integrity of the repaired tissue. In conclusion, these findings elucidate the detrimental effects of EHDPHP exposure on muscle differentiation, uncovering its muscle toxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}