Cell Biology and Toxicology最新文献

{"title":"IFI204 in microglia mediates traumatic brain injury-induced mitochondrial dysfunction and pyroptosis via SENP7 interaction.","authors":"Ting Guo, Yongxing Lai, Shuguang Wu, Chunjin Lin, Xinyu Zhou, Peiqiang Lin, Mouwei Zheng, Jianhao Chen, Fan Lin","doi":"10.1007/s10565-025-10032-8","DOIUrl":"10.1007/s10565-025-10032-8","url":null,"abstract":"<p><strong>Objectives: </strong>Traumatic brain injury (TBI) is a primary contributor to chronic functional impairment in human populations, initiating complex neuroinflammatory cascades and neurodegeneration. Despite extensive research efforts, the precise pathophysiological pathways remain incompletely characterized. This investigation aims to establish a novel therapeutic strategy that targets critical molecular pathways post-injury, potentially addressing the current limitations in the clinical management of TBI patients.</p><p><strong>Methods: </strong>The single-cell data of cortical tissue from mice with TBI were obtained from public databases (GSE160763), which was utilized to identify alterations in in the composition of disease-associated cells and related molecules as the disease progresses. Functional and pathway enrichment analyses were conducted to elucidate the functional characteristics of microglia and astrocyte subpopulations. Trajectory analysis was employed to investigate cell differentiation characteristics. Subsequently, we examined the expression and function of microglia-specific molecules, such as IFI204, along with their underlying molecular mechanisms using Western blotting, immunofluorescence, co-immunoprecipitation (CO-IP), histopathology, behavioral tests, and molecular docking to assess binding status, as well as molecular dynamics simulations. Finally, we used molecular docking technology to find small molecule compounds that IFI204 can stably bind to.</p><p><strong>Results: </strong>We identified nine major cell populations, most of which undergo dynamic changes following TBI. Astrocytes and microglia were the predominant populations in each group, and further cluster analysis revealed that the proportions of interferon (IFN) and axonogenesis-related microglial subtypes increased after TBI. Trajectory inference analysis indicated that the expression of Ifi204 is upregulated in microglia during disease progression. Conditional microglial knockdown of IFI204 significantly improved neurological deficits in mice, and alleviated mitochondrial dysfunction and microglial pyroptosis. Mechanistically, SENP7, identified as a novel molecule, interacts with IFI204 in microglia, catalyzes the deSUMOylation of IFI204, and promotes STING signal activation, ultimately driving microglial pyroptosis and mitochondrial dysfunction.</p><p><strong>Conclusions: </strong>The interaction between IFI204 and SENP7 promotes microglial pyroptosis and related mitochondrial dysfunction. Furthermore, in the case of TBI, we hypothesize that targeting IFI204 might yield therapeutic benefits.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"89"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126804","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":"Advancing oral cancer care: nanomaterial-driven diagnostic and therapeutic innovations.","authors":"Yuwen Chen, Sijia Cai, Fa-Yu Liu, Ming Liu","doi":"10.1007/s10565-025-10027-5","DOIUrl":"10.1007/s10565-025-10027-5","url":null,"abstract":"<p><p>The advent of nanotechnology has significantly advanced the diagnosis and treatment of oral cancer, offering more precise and efficient therapeutic strategies. This review presents a comprehensive overview of recent developments in the application of nanotechnology to oral cancer management. It begins with an overview of the epidemiology of oral cancer and outlines current diagnostic and therapeutic methods. The classification and advantages of various nanomaterials are then introduced. The paper thoroughly explores the use of nanomaterials as drug delivery systems (DDSs), imaging contrast agents, and therapeutic tools, with particular emphasis on multifunctional nanoplatforms that integrate diagnostics and therapy. These platforms enable real-time monitoring and immediate therapeutic response, offering innovative approaches for early detection and intervention. Despite these promising advances, several challenges persist, including issues related to biocompatibility, clearance, targeting specificity, and clinical translation. The review concludes by highlighting current limitations and proposing future directions for the clinical application of nanotechnology in oral cancer treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"90"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126795","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":"A novel tsRNA signature -tRF-58:76-Tyr-GTA-2-M3 as potential biomarker and therapeutic target for duodenal atresia.","authors":"Xinyue Meng, Xiaowei Wei, Hui Gu, Wei Ma, Dan Liu, Shanshan Jia, Songying Cao, Dongxue Ding, Yiwen He, Wanqi Huang, Jia Xue, Wenting Luo, Wei Sun, Zhengwei Yuan","doi":"10.1007/s10565-025-10040-8","DOIUrl":"10.1007/s10565-025-10040-8","url":null,"abstract":"<p><p>Duodenal atresia (DA) is a common neonatal digestive tract obstruction, with unclear prenatal diagnostic specificity and optimal intervention timing. tRNA-derived small RNAs (tsRNAs), stable and enriched in blood, are promising biomarkers for disease diagnosis. Therefore, identifying tsRNA biomarkers, elucidating DA pathogenesis, and exploring potential intrauterine interventions is urgently needed. This study conducts tsRNA profiling via sequencing on plasma samples from pregnant women carrying fetuses with DA and matched healthy controls. Validation was performed in 147 pregnant women, including cohorts with fetal gastrointestinal atresia, normal pregnancies, and post-delivery cases. Functional analyses in cellular models and Adriamycin rat models with DA explored the role of key tsRNAs in DA pathogenesis and intrauterine therapy. It is found that tsRNAs, including tRF-61:78-chrM. Leu-TAA, tRF-60:77-Ile-AAT-1-M4, tRF-57:76-Arg-ACG-1-M2, and tRF-58:76-Tyr-GTA-2-M3, were significantly downregulated in DA cases. tRF-58:76-Tyr-GTA-2-M3 is further implicated in DA development, with knockdown inducing excessive apoptosis via upregulation of SUFU and suppression of GLI1, a hedgehog pathway transcription factor. Intraperitoneal microinjection of tRF-58:76-Tyr-GTA-2-M3 agomir in DA rat models reduce apoptosis and mitigates DA formation by modulating SUFU and GLI1 expression. Taken together, this study identifies novel tsRNA biomarkers for DA, with tRF-58:76-Tyr-GTA-2-M3 playing a pivotal role in its pathogenesis. These findings offer insights into DA mechanisms and suggest potential therapeutic targets, advancing strategies for early diagnosis and intervention.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"88"},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118979","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":"METTL3-mediated m⁶A methylation in cardiac diseases: pathogenic roles and therapeutic potential.","authors":"Ruida Liu, Xiaojuan Su, Lei Yang, Dongqiong Xiao","doi":"10.1007/s10565-025-10039-1","DOIUrl":"10.1007/s10565-025-10039-1","url":null,"abstract":"<p><p>Cardiac dysfunction is a leading cause of death each year, putting heavy burdens on the global healthcare system. To improve our understanding of cardiac disease, novel perspectives for exploring their pathogenesis mechanisms are needed, which contributes to finding novel diagnoses and therapy targets for cardiac disease. To be noteworthy, researchers have paid great attention to understanding the pathogenesis of cardiac diseases from the perspective of methyltransferase-like 3 (METTL3, the catalytic core)-mediated RNA N⁶-methyladenosine modification and targeting METTL3 for therapy. Therefore, we aim to evaluate the significance of METTL3 in cardiac diseases. In the present review, we summarize and analyze all studies reporting the involvement of METTL3 in cardiac diseases (acute myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, and cardiac fibrosis) to interpret their interrelationship. This review suggests that METTL3 is a risk gene for cardiac diseases, which shows great promise as a disease diagnosis and prognosis biomarker and is poised to serve as an important target in drug development. Collectively, this review presents a comprehensive, cutting-edge overview of METTL3 in cardiac diseases, which could be a valuable reference for researchers to understand disease pathogenesis and develop novel drugs.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"87"},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109849","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":"Neuron-like macrophage differentiation via the APOE-TREM2 axis contributes to chronic pain in nasopharyngeal carcinoma.","authors":"Hongxi Li, Lanqing Zhao, Jinwei Li, Kailin Zhang, Weiliang Bai, Yu Chen","doi":"10.1007/s10565-025-10035-5","DOIUrl":"10.1007/s10565-025-10035-5","url":null,"abstract":"<p><p>Chronic pain is a prevalent and debilitating symptom in patients with nasopharyngeal carcinoma (NPC). Fresh insights indicate that tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) may undergo neuron-like differentiation, potentially contributing to pain mechanisms. By examining the apolipoprotein E (APOE) together with the triggering receptor expressed on myeloid cells 2 (TREM2), this study aims to clarify their joint function in modulating differentiation and how this interplay might be implicated in chronic pain associated with NPC. Through comprehensive analysis using TCGA-NPC transcriptomic datasets and single-cell RNA sequencing (scRNA-seq), we assessed the molecular landscapes of both NPC-affected and healthy nasopharyngeal tissues. Differential gene expression and immune cell profiling identified macrophages as key players in the inflammatory response. Single-cell sequencing revealed a distinct subpopulation of neuron-like macrophages expressing neurogenesis-related genes. Macrophage-to-neuron-like cell transformation in response to NPC cells was examined through in vitro co-culture systems, highlighting the involvement of the APOE-TREM2 regulatory pathway. In vivo studies involved macrophage depletion and TREM2 knockdown in mouse models to evaluate the impact on chronic pain development. Infiltrating macrophages were significantly more abundant in NPC samples, with many exhibiting neuron-like features that were positively linked to high levels of WNT5 A expression. In vitro, NPC cells induced macrophage differentiation into neuron-like cells, a process regulated by TREM2 and APOE. TREM2 knockdown in macrophages resulted in a reduction of chronic pain behaviors in mouse models, highlighting the contribution of the APOE-TREM2 Axis to NPC-associated chronic pain. Our findings demonstrate that NPC cells promote macrophage reprogramming through the APOE-TREM2 Axis, leading to neuron-like differentiation and contributing to chronic pain in NPC patients. Targeting this pathway may offer novel therapeutic strategies for managing chronic pain in NPC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"86"},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109866","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":"IGFBP3 enhances adipose-derived stem cell function in soft tissue injury repair via ITGB1 and ERK pathway activation.","authors":"Sirui Tian, Haiyang Yu, Ruoxuan Yang, Heshi Wang, Baohong Zhao, Danning Wang","doi":"10.1007/s10565-025-10024-8","DOIUrl":"https://doi.org/10.1007/s10565-025-10024-8","url":null,"abstract":"<p><p>Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"85"},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076220","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":"U2AF65 mediated circPVT1 promotes NSCLC cell proliferation and inhibits ferroptosis through the miR-338-3p/GPX4 axis.","authors":"Lujuan He, Zezhi Zhou, Jufen Wang, Jiehan Jiang, Shenggang Liu","doi":"10.1007/s10565-025-10028-4","DOIUrl":"10.1007/s10565-025-10028-4","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of circRNA expression is associated with increased metastasis and an adverse prognosis in non-small cell lung cancer (NSCLC). Herein, this study assessed the role and regulatory mechanism of circPVT1 in NSCLC development.</p><p><strong>Methods: </strong>CircPVT1 expression was determined using qPCR. Functional assays, including cell proliferation, colony formation, and ferroptosis-related measurements (ROS, MDA, SOD, GSH and Fe²⁺ levels), were conducted following circPVT1 knockdown. The interactions between RNA and protein were determined through RIP, dual-luciferase reporter and fluorescence in situ hybridization. Actinomycin D assay was employed to test circPVT1 stability. Additionally, tumor progression in vivo was evaluated in xenograft models with U2AF65 knockdown.</p><p><strong>Results: </strong>CircPVT1 was significantly elevated in NSCLC samples, correlating with worse clinical outcomes. Its knockdown resulted in diminished cell proliferation and increased ferroptosis. Mechanically, circPVT1 sponges miR-338-3p, facilitating GPX4 expression, which enhanced cell proliferation. U2AF65 bound to and stabilized circPVT1, promoting cell proliferation. In animal models, U2AF65 knockdown suppressed tumor progression by regulating the circPVT1/miR-338-3p/GPX4 signaling pathway.</p><p><strong>Conclusions: </strong>U2AF65 stabilizes circPVT1 to promote NSCLC advancement through miR-338-3p suppression and GPX4 upregulation. Thus, circPVT1 and U2AF65 may be potential therapeutic targets in NSCLC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"84"},"PeriodicalIF":5.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985776","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":"Activation of CaMKII⁺ neurons in the paramedian raphe nucleus promotes general anesthesia in male mice.","authors":"Xuehan Li, Zhixiong Ma, Xueliang Liu, Chen Chen, Ziqing Yu, Di Sang, Tongfei Wang, Eric Erquan Zhang, Guangyou Duan, Dapeng Ju, He Huang","doi":"10.1007/s10565-025-10037-3","DOIUrl":"10.1007/s10565-025-10037-3","url":null,"abstract":"<p><p>General anesthesia (GA) is an essential clinical and surgical adjunct, widely recognized as the result of coordinated networks among numerous brain regions. Anesthetic drugs with different characteristics are associated with distinct networks of brain regions involved in anesthesia. Ciprofol, a novel intravenous anesthetic derived from structural modifications of propofol, has shown promise in clinical applications. However, the specific neuronal circuits and brain regions mediating their actions may differ. Moreover, the core brain regions that mediate the common anesthetic effects of these drugs remain unclear. In this research, we identified a central ensemble of brainstem neurons within the paramedian raphe nucleus (PMnR) using c-Fos staining in mice subjected to GA induced by continuous intravenous infusion of ciprofol and propofol. This neuronal population, primarily composed of CaMKIIa and Gad1-expressing cells, demonstrated consistent activation in reaction to ciprofol. Optogenetic activation of PMnR^CaMKIIa neurons induced a GA state under ciprofol pre-administration, while sole activation of PMnR^CaMKIIa neurons induced a motionless state in mice. In addition, conditional inhibition of these neurons resulted in resistance to GA. In summary, we highlight the PMnR as a brain target for ciprofol and propofol. Furthermore, CaMKIIa⁺ neurons in the PMnR emerge as active promoters of the anesthesia process, shedding light on a previously unrecognized key player in the intricate neural network orchestrating GA.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"83"},"PeriodicalIF":5.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984850","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":"Rap2a promotes cardiac fibrosis and exacerbates myocardial infarction through the TNIK/Merlin/YAP axis.","authors":"Zhibin Lang, Xiaozhen Fan, Lin Qiu, Shuhui Hou, Junhui Zhou, Hongqi Lin","doi":"10.1007/s10565-025-10036-4","DOIUrl":"https://doi.org/10.1007/s10565-025-10036-4","url":null,"abstract":"<p><p>Myocardial fibrosis constitutes the primary pathological characteristic of myocardial infarction (MI). The activation and proliferation of myocardial fibroblasts serve as crucial factors in the process of the development of fibrosis in the myocardium. Our research delved into the role that Rap2a plays in cardiac function as well as myocardial fibrosis, while its effects on cardial fibroblasts (CFs) proliferation, migration, and phenotypic transformation were also explored. Examination of the GEO database showed a notable increase in the expression of Rap2a within myocardial tissue from mice with MI compared to normal mice. Rap2a deficiency relieves MI in mice and restrains the phenotypic transition, proliferation, and migration of CFs. The absence of Rap2a mitigates MI in mice. Besides, it curbs the growth of CFs, restricts their movement, and prevents them from undergoing phenotypic conversion. Rap2a can bind to TNIK in myocardial fibroblasts and enhance TNIK expression; Merlin/YAP signaling pathway was assessed as a downstream target of TNIK to further elucidate the regulatory mechanism through which Rap2a influences cardiomyocytes. In conclusion, this study provides evidence that Rap2a promotes myocardial fibrosis through mediating the myofibroblast transformation, proliferation, and migration of CFs via the TNIK/Merlin/YAP pathway, thereby exacerbating symptoms of myocardial infarction.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"80"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980452","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":"Panoramic lead-immune system interactome reveals diversified mechanisms of immunotoxicity upon chronic lead exposure.","authors":"Yifan Hong, Tianbao Ye, Hui Jiang, Aiting Wang, Boqian Wang, Yiyang Li, Haiyang Xie, Hongyu Meng, Chengxing Shen, Xianting Ding","doi":"10.1007/s10565-025-10034-6","DOIUrl":"https://doi.org/10.1007/s10565-025-10034-6","url":null,"abstract":"<p><p>Lead exposure is of high prevalence, and over a billion people are chronically exposed to alarming level of lead. Human immune system is highly vulnerable to lead, but the underlying mechanism remains unknown. Using single-cell mass cytometry and mass spectrometry-based proteomics, we performed a panoramic survey of lead targets at both cellular and molecular levels in murine immune system upon chronic lead exposure. We produced a single-cell landscape of lead, thiol metabolism and lead-induced toxicity across all immune cell types. We found that immune cells with extreme thiol metabolism are the most sensitive upon chronic lead exposure. It shows that CD4 + T cells and neutrophils are the most sensitive to lead, which is due respectively to a molecular mechanism rooted in their characteristic thiol metabolic capacity. Meanwhile, we found that lead accumulation by RBC further inflicted secondary toxicity to RBC phagocytes in spleen, e.g. macrophages and neutrophils. Unlike CD4 + T cells, which can be rescued by supplementation with thiol chelator, lead toxicity in these phagocytes cannot be effectively mitigated by thiol chelators. Overall, it forms a multiscale panoramic lead-immune system interactome upon chronic lead exposure, which provides valuable information for proactive prevention, therapy formulation and public health evaluation.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"81"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960167","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}