Cell Biology and Toxicology最新文献

{"title":"NFE2L2 suppresses microglia-mediated neuroinflammation to preserve neuronal dendritic architecture from cadmium-induced damage.","authors":"Siyao Li, Xue Wang, Xiaolong Ma, Rui Ding, Bingcheng Cai, Huimin Song, Yin Chen, Dianqi Yao, Yanyan Chen, Xing Zhang, Yuanyuan Xu, Yi Wang","doi":"10.1007/s10565-026-10178-z","DOIUrl":"10.1007/s10565-026-10178-z","url":null,"abstract":"<p><p>Cadmium (Cd), a widespread environmental toxic metal, is linked to central nervous system dysfunction and neuronal structural damage, yet its mechanisms remain unclear. This study combined network toxicology with experimental validation to explore how Cd impairs dendritic integrity through neuroinflammatory pathways. Network analysis suggested that Cd-induced dendritic injury was likely mediated by inflammatory signaling pathways, with nuclear factor-erythroid 2-related factor 2 (Nfe2l2), a major redox regulator, highlighted as a candidate regulator. Therefore, we investigated the involvement of microglia-mediated neuroinflammation in Cd-induced dendritic damage and assessed the role of Nfe2l2 in this process, using Nfe2l2 knockout mice and Nfe2l2 knockdown BV2 microglia. Furthermore, primary neurons were co-cultured with conditioned media (CM) from Cd-treated microglia to evaluate how Nfe2l2-regulated neuroinflammation contributes to dendritic damage. Nfe2l2 deficiency aggravated Cd-induced dendritic damage in the hippocampus, manifested as significant reductions in dendritic length, intersections, and branch points. In parallel, Nfe2l2 deficiency also intensified Cd-induced microglial activation and neuroinflammation in the hippocampus. Consistently, Nfe2l2 knockdown amplified Cd-induced BV2 microglial activation, characterized by increased migratory and phagocytic activity, and the subsequent cytokine release. Subsequently, CM derived from these activated microglia further exacerbated neuronal dendritic damage. Moreover, Nfe2l2 knockdown diminished minocycline's anti-inflammatory and neuroprotective effects. These results demonstrate that Cd-induced microglial activation and inflammation are central to dendritic injury, and that Nfe2l2 is essential in protecting neurons from Cd-driven neuroinflammation.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage exosomal ADAM10 mediates alveolar epithelial apoptosis induced by wood smoke PM_2.5.","authors":"Na Zhan, Yufeng Wang, Ru Liang, Yousen Wu, Ting Huang, Yuquan Ling, Xinbei Chen, Jiacheng Deng, LiFen Zhou, Kangni Luo, Yilin Cai, Yong-Sheng Tu, Lihui Qu, Jianhua Li","doi":"10.1007/s10565-026-10179-y","DOIUrl":"10.1007/s10565-026-10179-y","url":null,"abstract":"<p><p>Wood smoke (WS)-derived PM_2.5 is a major environmental risk factor for emphysema, but the role of macrophage-derived exosomes remains unclear. Here, we show that chronic WS exposure in rats induces emphysematous lesions accompanied by markedly increased exosome release, reflected by elevated CD63 expression in alveoli and increased exosome particle number in bronchoalveolar lavage fluid. Pharmacological inhibition of exosome secretion with GW4869 significantly attenuated alveolar destruction. Moreover, intranasal administration of exosomes from PM_2.5-exposed macrophages was sufficient to recapitulate emphysematous pathology in vivo. Mechanistically, PM_2.5 exposure upregulated the membrane-trafficking protein SNAP23 in macrophages, enhancing exosome secretion and increasing total abundance of ADAM10 within exosomes. Co-localization of CD63 and ADAM10 was observed in alveolar regions of WS-exposed rats and COPD patient lungs. Silencing ADAM10 suppressed caspase-3 activation and reduced epithelial apoptosis, supporting a role for exosomal ADAM10 in driving caspase-3-dependent alveolar epithelial injury. By defining an exosome-mediated macrophage-epithelium pathway that contributes to PM_2.5-induced emphysema, this study clarifies how combustion-derived PM_2.5 damages lung structure and offers mechanistic insight to reducing the health burden of biomass-related air pollution.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m6A-circRNA axis: a therapeutic prospect for gastric cancer.","authors":"Zijia Li, Yiwei Gu, Hui Gu, Qing-Bai She, Yuxin Tong","doi":"10.1007/s10565-026-10184-1","DOIUrl":"10.1007/s10565-026-10184-1","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major global health burden, and resistance to conventional therapies continues to limit durable clinical benefit. Increasing evidence identifies the N6-methyladenosine (m6A)-circular RNAs (circRNAs) axis as a critical regulatory network driving GC progression and therapeutic resistance. The functional interplay between m6A RNA modification and circRNAs contributes to key oncogenic processes, including chemoresistance, immune evasion, metabolic reprogramming, and resistance to cell death. In particular, m6A-modified circRNAs promote tumor progression by enhancing transcript stability, facilitating oncogenic signaling, modulating immune checkpoint pathways, and supporting metabolic adaptation under therapeutic stress. In this review, we synthesize current advances in understanding the mechanistic and translational significance of the m6A-circRNA axis in GC. We examine how this regulatory interface orchestrates adaptive resistance and evaluate emerging therapeutic strategies aimed at targeting its components. Modulating the m6A-circRNA axis-either as a standalone approach or in combination with existing treatments-represents a promising strategy to overcome multidrug resistance and improve clinical outcomes in GC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12^Arg185 fuels Relb-TNFSF14-mediated ductular reaction.","authors":"Jie Wang, Zihang Yuan, Haoran Zhang, Qianhui Tang, Yingying Miao, Anqin Li, Qingyu Chen, Xiaoyan Zhou, Qinwei Yu, Luyong Zhang, Zhenzhou Jiang","doi":"10.1007/s10565-026-10176-1","DOIUrl":"10.1007/s10565-026-10176-1","url":null,"abstract":"<p><p>For individuals with Primary Biliary Cholangitis (PBC) who are either intolerant or nonresponsive to ursodeoxycholic acid (UDCA), obeticholic acid (OCA) is authorized as a therapeutic treatment. Nevertheless, its clinical application has been limited due to the occurrence of several adverse effects. We employed the bile duct ligation (BDL) model to simulate cholestatic conditions observed in patients, revealing that high doses of OCA exacerbated hepatic inflammatory infiltration and fibrosis, accompanied by a marked augmentation in the extent of ductular reaction (DR) within BDL. Our findings mentioned that macrophages played a critical part in mediating OCA-induced aggravation of DR. OCA significantly upregulated the non-canonical NF-κB Relb signaling in macrophages, thereby contributing to proliferation of cholangiocytes. Cellular thermal shift assay (CETSA), surface plasma resonance (SPR) and liquid chromatography mass spectrometer (LC-MS) analysis showed that OCA directly bond to Nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain (PYD)-containing protein 12 (NLRP12), leading to a reduction in its protein level. Further, activity-based protein profiling (ABPP) method identified the Arg185 residue of NLRP12 as the binding site for OCA, elucidating the mechanism by which OCA downregulates NLRP12 protein expression. This interaction diminished the inhibitory effect of NLRP12 on the Relb pathway. Collectively, our study delineated the NLRP12^Arg185-Relb-TNFSF14 axis in macrophages as a key mechanism underlying OCA-induced hepatotoxicity.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meis1-driven suppression of MIF/CD74 signaling promotes M2 macrophage polarization and protects against inflammatory damage in experimental acute lung injury.","authors":"Gui Na Wang, Si Liu, Wei Xu","doi":"10.1007/s10565-026-10166-3","DOIUrl":"10.1007/s10565-026-10166-3","url":null,"abstract":"<p><p>Acute lung injury (ALI) is marked by dysregulated inflammatory responses, disruption of the alveolar-capillary barrier, and defective tissue repair, in which macrophages function both as drivers of tissue damage and facilitators of resolution. Here, we explored the transcriptional regulation of macrophage polarization in ALI using integrative single-cell and bulk RNA sequencing approaches. Meis1 was identified as a critical transcriptional factor that promotes macrophage skewing toward the M2 phenotype, associated with anti-inflammatory and reparative functions. Mechanistic dissection revealed that Meis1 negatively regulates the MIF/CD74 signaling pathway, thereby limiting pro-inflammatory macrophage activity. Experimental validation in vitro confirmed that Meis1 enhances expression of M2-associated markers while suppressing inflammatory cytokine release. In vivo studies using a murine ALI model demonstrated that Meis1 overexpression alleviates lung inflammation, reduces tissue damage, and accelerates structural repair. These findings establish Meis1 as a key modulator of immune cell fate in injured lungs. Through inhibition of MIF/CD74 signaling, Meis1 constrains inflammatory toxicity and supports tissue repair, revealing a novel regulatory pathway that may be exploited for treating ALI and related inflammatory lung conditions.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA m⁶A modification is a driver and therapeutic target in gastric cancer.","authors":"Qingjuan Chen, Hongzhao Lu, Dezhi Li, Tao Liu","doi":"10.1007/s10565-026-10141-y","DOIUrl":"10.1007/s10565-026-10141-y","url":null,"abstract":"<p><p>N6-methyladenosine (m⁶A), the most abundant modification in eukaryotic RNAs, plays a critical role in regulating RNA stability, expression, and translation. Key m⁶A regulators are up- or down-regulated in human gastric cancer tissues, by Helicobacter pylori and transcription factors, and the aberrant expression is associated with poor patient prognosis. Dynamic m⁶A modification, orchestrated by methyltransferases, demethylases, and m⁶A-binding proteins, profoundly impacts gastric cancer tumorigenesis, metastasis, cancer cell stemness, immune evasion, and resistance to chemotherapy, radiotherapy, and immunotherapy. While aberrant m⁶A modifications and the expression levels of its regulatory factors in blood samples are novel biomarkers in gastric cancer patients, therapies targeting m⁶A regulators have emerged as promising approaches for treating the disease. In summary, m⁶A RNA methylation represents a pivotal epitranscriptomic mechanism with significant implications for gastric cancer biology and precision oncology.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence and mechanism of gut microbiota on spermatogenesis.","authors":"Xinxing Zhou, Zhongli Ge, Xinyue Yang, Yujuan Liu, Yaoyun Li, Luning Chen, Liqiong Lv, Guanghui Chen","doi":"10.1007/s10565-026-10168-1","DOIUrl":"10.1007/s10565-026-10168-1","url":null,"abstract":"<p><p>Gut microbiota (GM) serves several functions in host, including immunological modulation, maintaining intestinal epithelial cell barrier and defending against pathogen invasion. Previous research has demonstrated that GM could regulate distal organs such as gut-brain and gut-liver axis. Recently, a rising number of researchers have discovered the substantial link between GM alteration and spermatogenesis disorder in male. This review highlights the phenomena of sperm production abnormalities caused by GM dysbiosis and the putative molecular pathways. Microbiota dysbiosis could lead to abnormal sperm production through multiple pathways. For example, the metabolic disturbance of vitamins impairs meiosis and spermatogenesis, upregulated miR-211-5p of extracellular vesicles inhibits meiosis and damages spermatogenesis, abnormal sphingolipid metabolite affects spermatogenic cell apoptosis, decreased short-chain fatty acid level causes inflammation and damages testicular tissue and reduced androgen level, resulting in spermatogenesis disorder. In addition, this review highlights therapeutic strategies, such as the administration of vitamins, probiotics, and prebiotics, for the treatment of spermatogenesis disorders associated with GM dysregulation. These insights underscore the importance of targeting the GM to preserve sperm quality and improve male reproductive health, offering promising future directions for the treatment of spermatogenic dysfunction and infertility.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gomisin B promotes RSL3-induced ferroptosis in neuroblastoma by inhibiting the ESR1/USP7/SREBF1 axis.","authors":"Mengyao Dong, Ting Gao, Yongtao Xu, Qinghao Li, Zhaolong Ma, Bin Zhao, Ming Ming","doi":"10.1007/s10565-026-10155-6","DOIUrl":"10.1007/s10565-026-10155-6","url":null,"abstract":"<p><strong>Background: </strong>Gomisin B was reported to alleviate neuroblastoma (NB) progression, and the promotion of ferroptosis also inhibited NB. This study aimed to investigate the mechanism by which Gomisin B regulates ESR1 to affect ferroptosis in NB.</p><p><strong>Methods: </strong>SH-SY5Y and IMR-32 cells were induced to ferroptosis by RSL3 and treated with Gomisin B. Co-IP was utilized to probe the relationship between USP7 and SREBF1. The interaction between ESR1 and USP7 was tested by dual luciferase reporter and ChIP. In addition, cell viability was assessed via CCK-8. Commercial kits were implemented to determine the MDA, GSH, Fe²⁺, and LPO levels. C-11 BODIPY 581/591 fluorescent probe was employed to examine lipid ROS level. BALB/c nude mice were used to construct NB animal models for in vivo studies.</p><p><strong>Results: </strong>Gomisin B promoted ferroptosis in NB cells and overexpression of ESR1 reversed this phenomenon. Additionally, ESR1 transcriptionally activated USP7 by interacting with the USP7 promoter to inhibit NB cell ferroptosis. USP7 facilitated SREBF1 deubiquitination by binding to SREBF1, thereby enhancing its protein stability. Gomisin B regulated the ESR1/USP7/SREBF1 axis to promote ferroptosis in NB cells. Finally, it was verified at the animal level that Gomisin B promoted ferroptosis and inhibited tumor growth in NB tumor-bearing nude mice.</p><p><strong>Conclusion: </strong>Gomisin B inhibited the transcriptional activation of USP7 by downregulating ESR1, thereby suppressing the deubiquitination of SREBF1. This enhanced NB ferroptosis to alleviate NB progression.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXO39 knockdown promotes spermatogenesis impairment by inducing mitochondrial dysfunction and ferroptosis via inhibiting KDM5A ubiquitination and regulating H3K4me3 demethylation.","authors":"Tao Li, Kun Wang, Yuxiang Chen, Zhuocheng Li, Shanda Li, Yu Zhang, Xuyuan Zhu, Haoran Shi, Liang Gao, Hongtao Jiang","doi":"10.1007/s10565-026-10167-2","DOIUrl":"10.1007/s10565-026-10167-2","url":null,"abstract":"<p><p>The global decline in male fertility highlights the need to understand the mechanisms of spermatogenesis. Mitochondrial dysfunction and ferroptosis have emerged as key contributors to spermatogenic impairment, although the molecular basis of this process is still poorly defined. F-Box Protein 39 (FBXO39), a testis-enriched F-box protein, has been preliminarily associated with cell survival. However, whether FBXO39 participates in mitochondrial functional regulation or ferroptosis signaling during spermatogenesis remains largely unexplored. In our study, FBXO39 knockdown resulted in abnormal testicular development, impaired spermatogenesis, abnormal sperm morphology, and reduced testicular cell viability. Further analysis revealed that FBXO39 deficiency caused mitochondrial dysfunction and ferroptosis, as reflected by decreased ATP production, reduced mitochondrial DNA content, elevated eactive oxygen species (ROS) levels, diminished expression of key mitochondrial proteins, and elevated lipid peroxidation. Mechanistically, FBXO39 maintains mitochondrial homeostasis by targeting lysine-specific demethylase 5A (KDM5A) for ubiquitination-dependent degradation. Conversely, the accumulation of KDM5A upon FBXO39 loss suppressed single-stranded DNA-binding protein 1 (SSBP1) levels through demethylation of Histone H3 lysine 4 trimethylation (H3K4me3) at the SSBP1 promoter. Importantly, restoration of SSBP1 expression functionally ameliorated mitochondrial dysfunction induced by FBXO39 knockdown. Overall, FBXO39 regulates mitochondrial function and ferroptosis in testicular cells through ubiquitinating KDM5A, which affects SSBP1 expression by modulating H3K4me3 demethylation at the SSBP1 promoter. This study elucidates the role of FBXO39 in spermatogenesis and suggested that targeting this regulatory axis may offer novel therapeutic strategies for male infertility.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene Nanoplastics induced placental toxicology by activating Keap1-mediated ferroptosis via METTL3-dependent m6A methylation.","authors":"Yujiao Chen, Yifan Liu, Meng Zhang, Shanshan Li, Yousheng Yan, Chenghong Yin","doi":"10.1007/s10565-026-10152-9","DOIUrl":"10.1007/s10565-026-10152-9","url":null,"abstract":"<p><p>Polystyrene nanoplastics (PS-NPs) exposure can induce placental toxicity, but the molecular mechanism of PS-NP-induced placental toxicity is poorly understood. We selected PS-NPs (80 nm) as a model of plastic particles and treated the human trophoblast cell line JEG3 (6.25, 12.5, 25, 50, and 100 mg/L) and pregnant mice with PS-NPs (15, 30 and 60 mg/kg·bw). These results found that PS-NPs regulated key ferroptosis-associated proteins (GPX4, ACSL4, and FTH1), indicating that PS-NPs induced ferroptosis. Here, we show for the first time that PS-NPs trigger placental ferroptosis by disrupting the p62-Keap1 interaction, thereby blocking Nrf2 degradation. Although m6A modification of the p62-Keap1-Nrf2 axis has been described in other models, its involvement in nanoplastic-induced placental injury remains unexplored. Here, we showed that PS-NPs induce ferroptosis by promoting METTL3 expression in JEG cells and placental tissues. Furthermore, knockdown of METTL3 inhibited PS-NP-induced ferroptosis by regulating Keap1 m6A, which inhibited the p62-Keap1-Nrf2 pathway in vitro. PS-NP-induced ferroptosis was attenuated by METTL3 knockdown via the inhibition of Keap1 m6A, which regulates the p62-Keap1-Nrf2 pathway. Collectively, these findings indicate thatMETTL3-mediated m6A methylation induced by PS-NPs may represent a previously unrecognized molecular basis for placental injury.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}