Life sciences最新文献

{"title":"Transcriptional and post-translational mechanisms of ECM remodeling in rotator cuff tendons under hyperlipidemic conditions","authors":"Resmi Rajalekshmi,&nbsp;Devendra K. Agrawal","doi":"10.1016/j.lfs.2025.123647","DOIUrl":"10.1016/j.lfs.2025.123647","url":null,"abstract":"<div><div>Rotator cuff injuries present significant clinical challenges, often resulting in chronic pain and functional impairment. In this study, we examined the effects of hyperlipidemia (HYP), a systemic metabolic condition, on tendon health. Histological analysis of infraspinatus tendons from hyperlipidemic swine revealed well-organized extracellular matrix (ECM) structures, comparable to those in non-hyperlipidemic (NONHYP) animals, suggesting ECM reorganization. Upstream SIGNOR3.0 analysis demonstrated that tumor necrosis factor receptor-associated factor 6 (TRAF6) activates transcription factor Yin Yang 1 (YY1) via kinase signaling, underscoring its role in tendon ECM remodeling. Hence, we futher examined the role of YY1, which is a critical regulator of collagen synthesis identified through network analysis. Although TRAF6 levels remained unchanged in HYP conditions, increased YY1 expression correlated with elevated COL1 gene expression. Additionally, twist-related protein 1 (TWIST1) emerged as another key molecule, existing in both homo- and heterodimer forms in NON-HYP conditions, but only as a heterodimer in HYP. YY1 enhanced COL1 transcription in the hyperlipidemic environment, while TWIST1 heterodimer formation facilitated collagen crosslinking. Notably, increased YY1 expression inhibited MMP3, resulting in the inactivity of MMP1, MMP8, and MMP9, thereby preserving collagen levels. These findings highlight the complex molecular interactions involving transcriptional regulation by YY1 and post-translational regulation by the TWIST1 heterodimer, essential for the deposition of mature collagen fibrils and driving tendon remodeling in hyperlipidemic conditions. This study offers valuable insights for the change of tendon health condition in hyperlipidemia disease or tendon pathology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123647"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update in non-alcoholic fatty liver disease management: role of sodium-glucose cotransporter 2 inhibitors","authors":"Oscar R. Zambrano-Vásquez ,&nbsp;Fernando Cortés-Camacho ,&nbsp;Jorge I. Castañeda-Sánchez ,&nbsp;Elena Aréchaga-Ocampo ,&nbsp;Estefanía Valle-Velázquez ,&nbsp;Juan C. Cabrera-Angeles ,&nbsp;José L. Sánchez-Gloria ,&nbsp;Fausto Sánchez-Muñoz ,&nbsp;Abraham S. Arellano-Buendia ,&nbsp;Laura G. Sánchez-Lozada ,&nbsp;Horacio Osorio-Alonso","doi":"10.1016/j.lfs.2025.123638","DOIUrl":"10.1016/j.lfs.2025.123638","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes without significant alcohol consumption. It is closely associated with sedentarism, hypercaloric diets, obesity, dyslipidemia, insulin resistance, type 2 diabetes mellitus, and genetic predisposition. NAFLD comprises a spectrum of liver disorders, from simple steatosis to non-alcoholic (NASH) and liver cirrhosis. The complex etiological mechanisms include oxidative stress, inflammation, apoptosis, and fibrosis; therefore, its management is challenging. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), a class of antidiabetic drugs, have emerged as promising therapeutic agents due to their ability to improve key metabolic parameters, including obesity, dyslipidemia, insulin resistance, and hyperglycemia. This review explores the cellular mechanisms by which SGLT2i, either as monotherapy or combined with other treatments, modulate signaling pathways involved in lipid and carbohydrate metabolism. Additionally, we examine their effects on oxidative stress, inflammation, fibrosis, and apoptosis, which are critical drivers of NAFLD progression. This review is intended to summarize the multiple benefits of SGLT2 inhibitors and to educate healthcare providers on the therapeutic potential of these drugs in order to foster their incorporation into effective NAFLD management plans.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123638"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircRNA encoded-peptide: Potential stock in the transcriptomics market","authors":"Siyuan Ma ,&nbsp;Sensen Su ,&nbsp;Xiuna Zhang ,&nbsp;Xiangxiu Wang ,&nbsp;Huanfa Yi","doi":"10.1016/j.lfs.2025.123643","DOIUrl":"10.1016/j.lfs.2025.123643","url":null,"abstract":"<div><div>The emergence of circRNA-encoded peptides has sparked significant debate in recent years as a novel mode of action for circRNAs. A mounting body of evidence suggests that these peptides play vital roles in cancer development and immune responses. This review initially elucidates the presence of circRNA-encoded peptides and delineates their specific functions across various biological processes and pathological conditions. It goes on to furnish illustrative instances to underscore the pivotal involvement of circRNA-encoded peptides in both innate and adaptive immune responses. The study sheds new light on the biological roles of circRNAs, their potential tumor-promoting and tumor-suppressing functions of circRNA-encoded peptides in specific tumor environment, and their significance in immunological contexts. Meanwhile, the limitations of existing studies on circRNA-encoded peptides are discussed in depth. In particular, circRNA-encoded peptides are critically analyzed as biomarkers and therapeutic targets. Intriguingly, the review concludes with a more organized discussion of future research on circRNA-encoded peptides.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123643"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long COVID in 2025: a clinical viewpoint","authors":"Andrew Schamess ,&nbsp;Markus Velten ,&nbsp;Aaron Friedberg","doi":"10.1016/j.lfs.2025.123633","DOIUrl":"10.1016/j.lfs.2025.123633","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123633"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEK2 supports porcine embryonic development by modulating the AKT signaling pathway","authors":"Se-Been Jeon ,&nbsp;Hyo-Gu Kang ,&nbsp;Min Ju Kim ,&nbsp;Ji Hyeon Yun ,&nbsp;Eun Young Choi ,&nbsp;Bong-Seok Song ,&nbsp;Sun-Uk Kim ,&nbsp;Seong-Keun Cho ,&nbsp;Pil-Soo Jeong ,&nbsp;Bo-Woong Sim","doi":"10.1016/j.lfs.2025.123640","DOIUrl":"10.1016/j.lfs.2025.123640","url":null,"abstract":"<div><h3>Aims</h3><div>Serine/threonine kinase NIMA-related kinase 2 (NEK2) plays a crucial role in regulating the cell cycle and DNA damage response. This study explored the mechanisms by which NEK2 inhibition affects porcine embryonic development.</div></div><div><h3>Materials and methods</h3><div>To explore the role of NEK2 in porcine embryonic development, we used the NEK2 inhibitor JH295 and the AKT activator SC79. Various staining methods, including EdU, EU, OPP, TUNEL assay, real-time PCR, immunocytochemistry, and Western blotting, were used to identify the effects of NEK2 inhibition on developmental competence, DNA damage, and the related mechanisms in porcine embryos.</div></div><div><h3>Key findings</h3><div>NEK2 inhibition significantly reduced the cleavage rate and blastocyst formation rate. Abnormal development was associated with decreased expression of genes related to zygotic genome activation and significantly reduced the levels of EdU, EU, and OPP. Notably, NEK2 inhibition decreased the levels of p-AKT and AKT, as well as their transcript levels. While NEK2 inhibition reduced the rates of cleavage and blastocyst formation as well as total cell number, all of these effects were reversed by SC79 co-treatment. The proportions of expanded blastocyst and cell survival and the trophectoderm cell numbers were similarly restored to control levels following combined treatment with SC79. Furthermore, the reduced levels of EdU, EU, and OPP by NEK2 inhibition were completely restored by SC79 co-treatment. NEK2 inhibition had a negative impact on DNA integrity, and this effect was inhibited by SC79 co-treatment.</div></div><div><h3>Significance</h3><div>Together, these results suggest that NEK2 plays a crucial role in porcine embryonic development by regulating the AKT signaling pathway.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123640"},"PeriodicalIF":5.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide amplifies the endocytosis of circulating exosomes derived from aortic dissection patients by the endothelial cells via a JMJD6 dependent manner","authors":"Qi Sun ,&nbsp;Junmei Xu ,&nbsp;Yujing Zhao,&nbsp;Lin Yang,&nbsp;Yulong Cui","doi":"10.1016/j.lfs.2025.123641","DOIUrl":"10.1016/j.lfs.2025.123641","url":null,"abstract":"<div><h3>Aim</h3><div>The underlying mechanism of endothelial dysfunction during the aortic dissection (AD) remains unclear. The present study is aimed to uncover the intrinsic mechanism regulating the endocytosis of circulating exosomes by endothelial cells after AD takes place.</div></div><div><h3>Material and methods</h3><div>Circulating exosomes extracted from both AD-patients and healthy donors (HD) were characterized and applied to human umbilical vein endothelial cells (HUVECs) in vitro with or without the co-exposure of lipopolysaccharide (LPS). The endocytosis of exosomes and inflammatory severity were evaluated. Besides, the JMJD6 expression pattern was explored, and si-RNA to knock down the JMJD6 expression was performed to test its role in exosome endocytosis.</div></div><div><h3>Key findings</h3><div>Here, it was firstly shown that circulating exosomes of the AD patients were statistically higher than the HD. In vitro, the endocytosis of both AD- and HD-exosomes was both enhanced under the co-existence of the LPS, and the uptake of AD-exosomes instead of the control exosomes further worsened the LPS-induced cell injury and gene transcriptions of serial pro-inflammatory cytokines through the p65 signaling. Notably, LPS challenged ECs exhibited increased JMJD6 expression, and silencing JMJD6 effectively decreased the LPS enhanced exosome endocytosis, and attenuated the LPS + AD-exosomes induced cell pro-inflammatory injury.</div></div><div><h3>Significance</h3><div>The findings above indicate that LPS co-exposure enhances the AD-exosomes endocytosis by the ECs and further aggravates the inflammatory injury; Targeting on the cellular JMJD6 shall mitigate AD-exosomes endocytosis, which might serve as a potential therapeutic approach for the endothelial dysfunction.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123641"},"PeriodicalIF":5.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roflumilast counteracts high-dose dexamethasone-induced steatohepatitis, metabolic abnormalities and aortic injury via inhibiting TNF-α/NF-κB, NLRP3/IL-1β and ER stress sensors","authors":"Mohammed Fulayyih Aloufi,&nbsp;Sara H. Hazem,&nbsp;Rania R. Abdelaziz,&nbsp;Ghada M. Suddek","doi":"10.1016/j.lfs.2025.123634","DOIUrl":"10.1016/j.lfs.2025.123634","url":null,"abstract":"<div><h3>Introduction</h3><div>High-dose dexamethasone (DEX) is used for management of severe conditions. However, the multisystem adverse effects induced by glucocorticoids represent a hindering stone toward the effective clinical use of such agents. Various initiatives have been taken to ameliorate these complications with limited success.</div></div><div><h3>Aim</h3><div>The present study aims to explore the beneficial effects of roflumilast (ROF), a phosphodiesterase-4 (PDE-4) inhibitor, to combat DEX-induced steatohepatitis, metabolic abnormalities and aortic degeneration.</div></div><div><h3>Results</h3><div>The application of ROF (2.5 and 5 mg/kg) has reverted the hepatic and aortic histopathological abnormalities as well as the rise in serum liver enzymes induced by DEX. Such palliative effect is probably attributed to PDE-4 inhibition (↑cAMP) that subsequently regulates multiple effectors. The chemotaxis of inflammatory cells (MCP-1) was inhibited by ROF treatments which was linked to inhibition of extracellular ROS production (MDA and NO) as well as restoration of cellular antioxidant defense (GSH). DEX challenge was associated with activation of the inflammatory pathways including TNF-α/NF-κB and NLRP3/IL-1β that were significantly dampened in the ROF groups. The oxidative stress as well as activation of inflammatory pathways exerted by DEX has contributed to the activation of endoplasmic reticulum stress (CHOP and PERK) posing more threats to the insulted cells, however, fortunately, ROF treatments showed inhibited activation of ER stress sensors and thereby abstaining the cells from inevitable damage. The metabolic abnormalities induced by DEX including elevated fasting insulin and heightened AUC of blood glucose level upon application of oral glucose tolerance test were significantly improved by ROF treatment.</div></div><div><h3>Conclusion</h3><div>The findings of our study depicted the hepatoprotective and metabolic regulating potentials of ROF in a rat model of DEX- induced steatohepatitis. Thereby, enhancing the overall efficacy and safety of DEX use in management of various disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123634"},"PeriodicalIF":5.2,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SETD1B promotes brain cell ferroptosis in ischemic stroke mice via increasing H3K4me3 enrichment on the Tfrc promoter","authors":"Li Wang ,&nbsp;Hong-Rui Liu ,&nbsp;Hui-Qi Liu ,&nbsp;Xi-Sheng Li ,&nbsp;Ting-Ting Tang ,&nbsp;Kai-Jia Wang ,&nbsp;Guang-Rong Wei ,&nbsp;Jing Tian ,&nbsp;Yi-Yue Zhang ,&nbsp;Xiu-Ju Luo","doi":"10.1016/j.lfs.2025.123625","DOIUrl":"10.1016/j.lfs.2025.123625","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates the role of SET domain containing 1B (SETD1B), a histone lysine methyltransferase, in promoting ferroptosis induced by ischemic stroke through the upregulation of transferrin receptor 1 (TfR1).</div></div><div><h3>Materials and methods</h3><div>An ischemic stroke model was established in C57BL/6J mice by subjecting them to 1 h of ischemia followed by 24 h of reperfusion. Brain damage was assessed by neurological impairment and infarct volume. Levels of SETD1B, TfR1, total iron, Fe²⁺, lipid peroxidation (LPO), ferritin (FPN), and GPX4 were measured. In vitro, HT22 cells were subjected to 14 h of oxygen-glucose deprivation (OGD) followed by 24 h of reoxygenation. SETD1B knockdown was performed to assess its impact on ferroptosis.</div></div><div><h3>Key findings</h3><div>In the ischemic stroke mice, SETD1B expression was elevated, accompanied by increased ferroptosis markers, including higher levels of TfR1, total iron, Fe²⁺, and LPO, as well as reduced levels of FPN and GPX4. These phenomena were observed in cultured HT22 cells under OGD/R conditions. SETD1B knockdown effectively reversed these effects, decreasing ferroptosis markers and reducing <em>Tfrc</em> expression via preventing H3K4me3 enrichment at the <em>Tfrc</em> promoter.</div></div><div><h3>Significance</h3><div>These findings suggest that SETD1B enhances ferroptosis in stroke brain cells by a mechanism involving boosting H3K4me3 enrichment at the <em>Tfrc</em> promoter and subsequent upregulation of the expression of <em>Tfrc</em>. Targeting SETD1B may provide a therapeutic strategy for mitigating ferroptosis in stroke.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123625"},"PeriodicalIF":5.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPP3CB inhibits pancreatic cancer progression by promoting ATOH8 translocation and transcriptionally regulating Sp1","authors":"Xiao Dong ,&nbsp;Lixia Wu ,&nbsp;Libao Gong ,&nbsp;Daijia Huang ,&nbsp;Jinfeng Guo ,&nbsp;Meng Ma ,&nbsp;Li Xiao ,&nbsp;Shuangwei Xu ,&nbsp;Jianhua Chang ,&nbsp;Xu Che ,&nbsp;Junjie Hang","doi":"10.1016/j.lfs.2025.123631","DOIUrl":"10.1016/j.lfs.2025.123631","url":null,"abstract":"<div><h3>Aims</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy which lacks effective therapeutic targets. We previously demonstrated that low PPP3CB expression correlates with poor prognosis in PDAC. This study aims to investigate the function and underlying mechanism of PPP3CB in pancreatic cancer progression.</div></div><div><h3>Materials and methods</h3><div>We analyzed PPP3CB expression via immunohistochemistry in PDAC specimens and investigated its prognostic value by statistical method. Differentially expressed genes were analyzed by qRT-PCR and Western blot. Mass spectrometry, Co-IP, ChIP-seq, luciferase analysis, flow cytometry, immunofluorescence and confocal microscopy were performed to investigate the underlying mechanisms of PPP3CB and regulation of ATOH8/Sp1 axis. Mice xenograft models were employed to assess the malignant behaviors in vivo.</div></div><div><h3>Key findings</h3><div>We found that PPP3CB expression was higher in patients with early-stage PDAC than in those with late-stage PDAC. PPP3CB overexpression impaired PDAC proliferation and metastasis in vitro and in vivo, whereas its depletion or treatment with CsA—a PPP3CB inhibitor, had the opposite effect. Liquid chromatography–tandem mass spectrometry predicted an interaction between PPP3CB and ATOH8. Further investigation confirmed that PPP3CB interacts with ATOH8 and enhances its nuclear translocation in PDAC cells. ChIP-seq and luciferase analyses showed that ATOH8 binds to the promoter of Sp1, a well-known oncogenic transcription factor in PDAC. Furthermore, PPP3CB transcriptionally inhibits Sp1 expression and suppresses pancreatic cancer metastases by increasing ATOH8 nuclear content.</div></div><div><h3>Significance</h3><div>These findings suggest a novel role for PPP3CB in preventing PDAC progression by promoting ATOH8 nuclear translocation and transcriptionally inhibiting Sp1. Consequently, PPP3CB emerges as a potential therapeutic target for PDAC.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123631"},"PeriodicalIF":5.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pyroptosis in environmental pollutants-induced multisystem toxicities","authors":"Rui Xu ,&nbsp;Longfei Li ,&nbsp;Yijia Ke ,&nbsp;Ziwen An ,&nbsp;Wenjing Duan ,&nbsp;Mingmei Guo ,&nbsp;Zhenzhen Tan ,&nbsp;Xuehui Liu ,&nbsp;Yi Liu ,&nbsp;Huicai Guo","doi":"10.1016/j.lfs.2025.123632","DOIUrl":"10.1016/j.lfs.2025.123632","url":null,"abstract":"<div><div>The global ecosystem is adversely affected by environmental pollutants, which have numerous deleterious consequences on both the environment and human health. A multitude of human organs and systems, including the neurological, digestive, cardiovascular, reproductive, and respiratory systems, can be adversely affected by these pollutants. Pyroptosis is a form of programmed cell death, primarily involving the Caspase-1/Gasdermin D (GSDMD) classical inflammasome pathway, Caspase-4/5/11/GSDMD non-classical inflammasome pathway, Caspase-3/8 pathway, and other signaling pathways, which induce cell death and regulate the occurrence of inflammatory responses. Pyroptosis plays an important role in a range of diseases, including cancer, neurodegenerative diseases and cardiovascular disease. Evidence has emerged in recent years indicating that environmental pollutants exert various toxic effects by modulating pyroptosis. In this review, we examine hepatotoxicity, cardiovascular toxicity, nephrotoxicity, neurotoxicity, pulmonary toxicity, reproductive toxicity and the related mechanisms caused by environmental pollutants through the regulation of pyroptosis. We aim to provide theoretical references for future toxicity research on environmental pollutants.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123632"},"PeriodicalIF":5.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}