JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Genetically Predicted PD1 and the Risk of Cardiovascular Diseases","authors":"Wenfei Chen,&nbsp;Kangnan Wang,&nbsp;Jun Chen,&nbsp;Lei Chen","doi":"10.1111/jcmm.70678","DOIUrl":"https://doi.org/10.1111/jcmm.70678","url":null,"abstract":"<p>Genetically speaking, ICI was mainly referred to as PD-1. We utilized a two-sample MR analysis model to assess the causative impact of PD1 on six kinds of CVDs, including coronary atherosclerosis, atrial fibrillation (AF), myocarditis, hypertrophic cardiomyopathy, dilated cardiomyopathy, and heart failure (HF). In this study, the IVW model as the primary MR approach revealed that genetically predicted PD1 has a causal impact on the increased risk of coronary atherosclerosis (OR, 1.062; 95% CI, 1.031–1.095, <i>p</i> = 6.81E-05), as well as myocarditis (OR, 1.177; 95% CI, 1.010–1.371, <i>p</i> = 0.037). However, genetically predicted PD1 does not significantly increase the risk of AF (OR, 1.024; 95% CI, 0.969–1.082, <i>p</i> = 0.398), HF (OR, 1.025; 95% CI, 0.971–1.081, <i>p</i> = 0.371), dilated cardiomyopathy (OR, 0.924; 95% CI, 0.819–1.044, <i>p</i> = 0.207), and hypertrophic cardiomyopathy (OR, 1.047; 95% CI, 0.838–1.308, <i>p</i> = 0.685). Our study found that genetically predicted PD1 has a causal impact on the increased risk of coronary atherosclerosis and myocarditis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Docking and Functional Analyses Reveal the Chondroprotective and Anti-Inflammatory Potential of Statins in Osteoarthritis","authors":"Bugrahan Regaip Kilinc,&nbsp;Feyza Kostak,&nbsp;Omer Faruk Yilmaz,&nbsp;Suray Pehlivanoglu,&nbsp;Duygu Yasar Sirin","doi":"10.1111/jcmm.70791","DOIUrl":"https://doi.org/10.1111/jcmm.70791","url":null,"abstract":"<p>Osteoarthritis is a progressive degenerative joint disorder characterised by cartilage degradation and chronic inflammation. Beyond their well-established lipid-lowering properties, statins, particularly pitavastatin and rosuvastatin, have demonstrated promising anti-inflammatory and chondroprotective effects. This study comprehensively evaluated these effects on human primary chondrocytes using an integrative approach involving in silico and in vitro experiments. Key molecular targets, including NF-κB, IL-1β and SOX9, were analysed to elucidate the mechanisms underlying the therapeutic potential of these statins. Molecular docking analyses using the CB-Dock2 platform revealed strong binding affinities of both statins with the target proteins, with pitavastatin exhibiting a higher binding score (−8.0) compared to rosuvastatin (−7.9). Bioinformatics analyses via STITCH and STRING databases highlighted the involvement of both statins in pathways regulating inflammation, lipid metabolism, and cartilage homeostasis. In vitro experiments demonstrated that both statins preserved chondrocyte viability at 24 and 48 h; however, prolonged exposure led to significant declines, with rosuvastatin exhibiting greater cytotoxicity. Western blot analyses confirmed that both statins effectively suppressed IL-1β expression, indicative of potent anti-inflammatory activity. Pitavastatin transiently enhanced SOX9 expression, peaking at 24 h before declining, while rosuvastatin showed a more sustained but moderate increase. NF-κB expression steadily increased over time with both statins, suggesting potential activation of compensatory inflammatory pathways during prolonged exposure. These findings underscore the dual anti-inflammatory and chondroprotective roles of pitavastatin and rosuvastatin, while highlighting the need for careful consideration of dosage and treatment duration to mitigate cytotoxic effects and provide novel insights into the molecular mechanisms of statins.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-20a-5p Inhibits Bladder Cancer Proliferation and Migration by Targeting KPNA2","authors":"Shuai Ye,&nbsp;Cen Liufu,&nbsp;Cong Yin,&nbsp;Tao Zhu,&nbsp;Jinqing He,&nbsp;Yuanyuan Tian,&nbsp;Yan Wang,&nbsp;Bentao Shi","doi":"10.1111/jcmm.70785","DOIUrl":"https://doi.org/10.1111/jcmm.70785","url":null,"abstract":"<p>Bladder cancer (BC) is one of the 10 most common cancers in the world, and its recurrence and metastasis are the main causes of death in BC patients. Exploring the molecular mechanisms of BC pathogenesis and searching for new prognostic markers and therapeutic targets are important for improving patient prognosis. KPNA2 was found to be a potential oncogene in different malignant tumours, as demonstrated in our previous study. To better understand the mechanisms associated with BC development, we investigated the inhibitory effect of miR-20a-5p on the oncogene KPNA2. RNA-seq data from BC patients were downloaded through the TCGA database for bioinformatics analysis, including gene expression, co-expression analysis, GSEA, nomogram modelling, functional enrichment analysis, WGCNA, GO and KEGG to assess the potential biological functions of miR-20a-5p in BC. Subsequently, we further verified the expression of miR-20a-5p in BC cells by RT-qPCR, and in vitro experiments were performed to investigate the effects of this gene on BC cell proliferation and migration. MiR-20a-5p was downregulated in BC tissues and cells. Kaplan–Meier analysis revealed that the higher the expression of miR-20a-5p in patients, the higher the survival rate of BC patients. MiR-20a-5p overexpression inhibited the proliferation and migration of BC cells. In addition, miR-20a-5p can directly bind to nuclear transporter protein α2 (KPNA2) in cells, targeting and regulating the expression of KPNA2. These findings indicate that miR-20a-5p targeting KPNA2 adversely affects the proliferation and migration of BC cells, suggesting that miR-20a-5p may be an attractive target in BC therapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX42 Enhances Hepatocellular Carcinoma Cell Proliferation, Radiation and Sorafenib Resistance via Regulating GRB2 RNA Maturation and Activating PI3K/AKT Pathway","authors":"Zijian Liu,&nbsp;Jingsheng Yuan,&nbsp;Fei Liu,&nbsp;Qiwen Zeng,&nbsp;Zhenru Wu,&nbsp;Jian Yang","doi":"10.1111/jcmm.70793","DOIUrl":"https://doi.org/10.1111/jcmm.70793","url":null,"abstract":"<p>The DEAD-box RNA helicase (DDX) family is one of the canonical splicing regulators, engaged in RNA metabolism, and generally participates in forming spliceosomes. However, systematic analysis of DDX family members in hepatocellular carcinoma (HCC) has not been conducted before, and their biological functions need to be investigated further. Based on biological function enrichment analysis, radiosensitivity index (RSI), and prediction IC50 index for sorafenib, we ultimately ascertain DDX42 as a candidate gene. DDX42 was highly expressed in HCC than in para-tumour tissues and was a prognostic factor for HCC patients. Importantly, DDX42 overexpression promotes cell proliferation, radio-resistance and sorafenib resistance in HCC cells and activates the PI3K/AKT pathway. Knockdown of DDX42 moderately inhibited cell growth of HCC cells and significantly increased radio-sensitivity, enhanced the efficacy of sorafenib, and inactivated the PI3K/AKT pathway. Mechanically, DDX42 could urge the mRNA maturation of GRB2, contributing to cell proliferation and enhancement of resistance ability to radiotherapy and sorafenib for HCC cells. Subcutaneous xenograft nude mouse model showed that DDX42 significantly promoted tumour growth as compared to the control group and lifted the expression of GRB2, KI-67 and PCNA in vivo. In conclusion, our findings facilitate the acknowledgment of tumour initiation and mechanisms of treatment resistance in HCC, and targeting the axis of DDX42 and GRB2 may be promising strategies for synergy with radiotherapy or sorafenib for HCC patients.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘TRAF6 Regulates Tumour Metastasis Through EMT and CSC Phenotypes in Head and Neck Squamous Cell Carcinoma’","authors":"","doi":"10.1111/jcmm.70750","DOIUrl":"https://doi.org/10.1111/jcmm.70750","url":null,"abstract":"<p>Chen L, Li YC, Wu L, Yu GT, Zhang WF, Huang CF, Sun ZJ. TRAF6 regulates tumour metastasis through EMT and CSC phenotypes in head and neck squamous cell carcinoma. <i>Journal of Cellular and Molecular Medicine</i> 2017; 22: 1337–1349. https://doi.org/10.1111/jcmm.13439</p><p>In Lei Chen et al., Figure 1, 2, 3, and 4 contained errors. The hematoxylin-eosin (HE) image of lymph node metastasis in Figure 1C, the Western blot images in Figures 2A, 3B and 4B and the transwell assay image of the negative control (NC) group in Figure 2F are incorrect. The correct images are shown below. These corrections do not alter the results or conclusions of the article. All authors have reviewed and approved these corrections.</p><p>We apologise for these errors.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate Lymphoid Cells Are the Rheostat of Immune Response in the Kidney","authors":"Sensen Su,&nbsp;Lei Wang,&nbsp;Han Qin,&nbsp;Hui Yu,&nbsp;Siyuan Ma,&nbsp;Yueming He,&nbsp;Xin Chen,&nbsp;Zhanchuan Ma,&nbsp;Heyuan Wang,&nbsp;Huanfa Yi","doi":"10.1111/jcmm.70782","DOIUrl":"https://doi.org/10.1111/jcmm.70782","url":null,"abstract":"<p>Kidney disease ranks as the seventh most significant and the third fastest-growing risk factor contributing to mortality globally. Innate lymphoid cells (ILCs) are tissue-resident immune cells that lack antigen-specific receptors and produce robust cytokines. ILCs play vital roles in infection, allergy, metabolic disorders, cancers, and tissue homeostasis. Recent studies have found that ILCs are manipulated for various kidney diseases. ILCs are classified into natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and regulatory ILCs (ILCregs). We mainly discuss ILC1s, ILC2s, and ILC3s in kidney diseases. ILC2s and ILC3s are distributed along the renal vessels, and ILC3s are involved in the formation of ectopic lymphoid structures. ILCs secrete a variety of active cytokines, which can directly act on renal parenchymal cells or recruit other immune cells to affect kidney disease. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are regulated by ILCs. ILC2s play a protective role in AKI and glomerulonephritis. Though ILC3s promote fibrosis in CKD, the roles of ILC2s in kidney fibrosis remain controversial. ILC1s and ILC3s promote glomerulonephritis. Kidney diseases will benefit from further studies focusing on the epigenetic/metabolic/neuron modulation and plasticity of ILCs.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70782","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Physiological and Pathological Mechanisms of LIN2, LIN7, LIN10 and Their Tripartite Complex","authors":"Yangyang Shang,&nbsp;Xinyi Gan,&nbsp;Yue Dang,&nbsp;Jie Liu,&nbsp;Peijun Liu","doi":"10.1111/jcmm.70794","DOIUrl":"https://doi.org/10.1111/jcmm.70794","url":null,"abstract":"<p>The LIN family represents a set of conserved proteins that are pivotal in the establishment of cell polarity, the development of synapses and signal transduction processes. Its members, polarity proteins LIN2, LIN7 and LIN10, interact with diverse target proteins via the PDZ domain, SH3-GK tandem domain and PTB domain. Through these interactions, they are actively engaged in the establishment and modulation of apical-basal polarity. Moreover, LIN2, LIN7 and LIN10, along with their associated complex LIN2/7/10, participate in the physiological phenomena of synaptic transmission and receptor localisation. In addition, from a pathological perspective, LIN2, LIN7 and LIN10 are intricately linked to the genesis and progression of type 2 diabetes, cardiovascular disorders and a wide spectrum of tumours. This review focuses on the polarity proteins LIN2, LIN7, LIN10 and their complex. It summarises the functions of these molecular domains, systematically arranges their regulatory mechanisms in both physiological and pathological contexts and summarises the current state of research on LIN2, LIN7, LIN10 and their complex. The objective is to furnish a robust theoretical foundation for the prospective utilisation of polarity proteins and their complex as cancer markers and therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Synergises the Chemotherapeutic Effect of Temozolomide in Glioblastoma by Suppressing NF-κB/COX-2 Signalling Pathways","authors":"Hong Tang,&nbsp;Qi Dai,&nbsp;Ziyan Zhao,&nbsp;Weiye Ge,&nbsp;Danlei Li,&nbsp;Zelin Chang,&nbsp;Penglai Pi,&nbsp;Jia Li,&nbsp;Zheng Sun","doi":"10.1111/jcmm.70778","DOIUrl":"https://doi.org/10.1111/jcmm.70778","url":null,"abstract":"<p>Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumour, accounting for a significant proportion of adult brain tumours. It is associated with a poor prognosis and high recurrence rates. Although temozolomide (TMZ) remains the standard first-line chemotherapy for GBM, its clinical efficacy is often limited by the development of drug resistance and toxic effects on normal tissues. Melatonin (Mel), a natural indoleamine synthesised by the pineal gland, has demonstrated synergistic anti-tumour effects when combined with various chemotherapy agents in multiple studies. This study investigates the synergistic potential of Mel to enhance TMZ's therapeutic efficacy against GBM. The results demonstrate that the combination of Mel and TMZ significantly inhibits glioblastoma cell proliferation, migration, and invasion. Mechanistically, this synergistic effect is mediated through the NF-κB/COX-2 signalling pathway. Mel enhances TMZ's anti-tumour activity by inhibiting IκBα phosphorylation, suppressing NF-κB activation, and downregulating COX-2 expression. Additionally, the combination treatment induced apoptosis via activation of the Caspase-3 pathway. These results suggest that Mel can potentiate the therapeutic efficacy of TMZ in glioblastoma treatment, offering a promising strategy to overcome TMZ resistance while reducing its associated toxicity.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM47 Facilitates Osteosarcoma Progression via Destabilising FBP1 and Thus Activation of Wnt/β-Catenin Pathway","authors":"Heng Wang,&nbsp;Xiao Chen,&nbsp;Fengting Nie,&nbsp;Min Zhong,&nbsp;Zhi Fang,&nbsp;Zezhi Qiu,&nbsp;Ling Zhou,&nbsp;Yi Le,&nbsp;Xianpin Wei,&nbsp;Yanyu Liao,&nbsp;Ziling Fang","doi":"10.1111/jcmm.70753","DOIUrl":"https://doi.org/10.1111/jcmm.70753","url":null,"abstract":"<p>Osteosarcoma is a malignant bone tumour with a high rate of disability and mortality in adolescents. Tripartite motif containing 47 (TRIM47) upregulation contributed greatly to carcinogenesis and progression in several tumours, while its role in osteosarcoma (OS) is still unclear and needs further investigation. In this study, we first evidenced that TRIM47 was frequently upregulated in osteosarcoma tissues and cell lines, and the higher TRIM47 expression predicted poor outcomes for osteosarcoma patients. Moreover, TRIM47 depletion impeded cell proliferation, migration, and invasion of osteosarcoma cells, while TRIM47 overexpression elicited opposite effects. Mechanistically, TRIM47 interacted with and accelerated the degradation of fructose 1, 6-bisphosphatase 1 (FBP1) by inducing its ubiquitination, subsequently activating the Wnt/β-catenin signalling pathway. Furthermore, knockdown of FBP1 reversed the functions of TRIM47 depletion in OS cells. More notably, our in vivo assays showed that loss of TRIM47 slowed the growth rate of osteosarcoma xenograft tumours. Overall, our data indicated that TRIM47 facilitates OS progression by promoting proteasomal degradation of FBP1, thereby activating the Wnt/β-catenin pathway, which clarified that targeting the TRIM47-FBP1-β-catenin axis could be a promising approach for treating OS.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfiram Protects Against Multiorgan Injuries and Cell Pyroptosis via Inhibiting GSDMD in Severe Acute Pancreatitis Mice","authors":"Tianming Zhao,&nbsp;Si Zhao,&nbsp;Rui Fang,&nbsp;Yu Liu,&nbsp;Jing Ding,&nbsp;Xiaoxiao Shi,&nbsp;Shupei Li,&nbsp;Dan Xu,&nbsp;Xiaotan Dou,&nbsp;Mingdong Liu,&nbsp;Haijun Wan,&nbsp;Kang Jiang,&nbsp;Yuzheng Zhuge,&nbsp;Lei Wang,&nbsp;Hao Zhu,&nbsp;Lin Zhou","doi":"10.1111/jcmm.70707","DOIUrl":"https://doi.org/10.1111/jcmm.70707","url":null,"abstract":"<p>Severe acute pancreatitis (SAP) is distinguished by an uncontrolled systemic pro-inflammatory response caused by the activation of trypsin within the pancreatic tissue, leading to the occurrence of multiple organ failure (MOF). Gasdermin D (GSDMD)-induced pyroptosis represents a form of programmed cell death characterised by robust inflammatory responses. This indicates that directing efforts towards pyroptosis could potentially offer a remedy for SAP and its related MOF. Our objective was to examine the impact of disulfiram (DSF), a potent inhibitor of pyroptosis, and its potential therapeutic mechanism in SAP. The biochemical and histological assessments provided clear evidence that DSF effectively hindered necrosis, infiltration, oedema and cellular demise within pancreatic tissues. As a result, DSF effectively suppressed acute pancreatitis. Significantly, DSF hindered the process of GSDMD-mediated pyroptosis in pancreatic cells within the context of SAP. This is evident through the observed decrease in the number of SYTOX-positive cells, the prevention of LDH release and the restriction of expression of full-length GSDMD, N-terminal GSDMD and p-NF-ĸB p65. Subsequently, we assessed the mRNA levels of the pro-inflammatory cytokines Il-18, Il-1β, Il-6, Tnf-α, Hmgb1 and Ccl2. Our findings revealed a significant rise in the levels of these pro-inflammatory cytokines in SAP mice, whereas DSF remarkably inhibited the release of them. It is noteworthy that DSF also mitigated the resultant damage to remote vital organs (lungs, liver, and kidneys). Thus, GSDMD-mediated pyroptosis has been significantly involved in the pathogenesis of SAP, and DSF could potentially serve as an alternative therapeutic agent for SAP and its associated MOF.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 15","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}