Journal of Cellular and Molecular Medicine最新文献

{"title":"Identification of Key Genes Involved in Lactic Acid Metabolism in Periodontitis Based on Bioinformatics Analysis.","authors":"Bijun Zhu, Shi Xu, Mingyue Cheng, Leiying Miao","doi":"10.1111/jcmm.71141","DOIUrl":"10.1111/jcmm.71141","url":null,"abstract":"<p><p>Lactic acid metabolism correlates with periodontitis progression. Using machine learning (LASSO and SVM-RFE) on GSE16134 and GSE173078 datasets, CFI and COQ2 were identified as key genes, with good diagnostic performance (AUC > 0.75). GSEA linked these genes to MAPK signalling, endocytosis, and ubiquitin-mediated proteolysis. Immune infiltration analysis revealed higher plasma cells and lower CD8 T cells in periodontitis. Molecular docking identified amiodarone as a potential compound with strong binding affinity to CFI and COQ2. The expression trends of CFI (upregulated) and COQ2 (downregulated) were first confirmed in TNF-α/IL-1β-stimulated human periodontal ligament cells and further validated in a rat ligature-induced periodontitis model. These findings suggest that CFI and COQ2 are potential diagnostic biomarkers and therapeutic targets for periodontitis.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71141"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716818","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":"Emerging Therapeutic Strategies in Oral Cancer: Epigenetic, Mitochondrial and Immunotherapy Approaches.","authors":"Geetha Shanmugam, Carmelin Durai Singh, Rekha Thiruvengadam, Muthu Thiruvengadam, Vitaly Morozov, Roman Kolesnikov, Ali Alkaladi, Rashad Saleh, Mohammad Ali Shariati","doi":"10.1111/jcmm.71107","DOIUrl":"10.1111/jcmm.71107","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and poses treatment challenges owing to genetic, epigenetic and environmental factors. Conventional treatments, including surgery, chemotherapy and radiation therapy, often have limitations in terms of efficacy and tolerability. Advances in epigenetic therapies such as DNA methyltransferase and histone deacetylase inhibitors offer promising avenues for reversing abnormal gene expression in OSCC. Mitochondria-targeted therapies leverage metabolic disruption and reactive oxygen species modulation to induce apoptosis. Immunotherapy, particularly with immune checkpoint inhibitors and cancer vaccines, enhances the immune response against cancer cells. This review explores the interplay between the tumour microenvironment and oral microbiome in OSCC progression and treatment response. Additionally, RNA interference therapy and nanoparticle-based drug delivery systems enable targeted therapeutic strategies, reduce off-target effects and improve efficacy. Although these approaches show potential, challenges in clinical translation remain. The integration of precision medicine with innovative drug delivery systems can significantly improve patient outcomes in oral cancer management.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71107"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771526","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":"CTSC Confers Radioresistance in Hepatocellular Carcinoma by Regulating Myeloid-Derived Suppressor Cells.","authors":"Jiahuan Xu, Bilin Zhang, Shirui Yang, Shaoran Song, Jie Wu, Yunzhi Dang","doi":"10.1111/jcmm.71153","DOIUrl":"10.1111/jcmm.71153","url":null,"abstract":"<p><p>Radiotherapy is an important therapeutic modality for advanced hepatocellular carcinoma (HCC), but the limited understanding of radioresistance mechanisms in HCC has hindered its further clinical development. This work aimed to clarify the essential role of Cathepsin C (CTSC) in regulating radioresistance in HCC. The expression of CTSC in HCC tissues was analysed using real-time PCR (RT-PCR) and immunohistochemistry. The role of CTSC in radiotherapy resistance of HCC was investigated through in vitro experiments, in vivo studies (subcutaneous and orthotopic liver tumour models) and clinical data analysis. Additionally, in vivo experiments were conducted to evaluate the effect of blocking the CTSC signalling pathway on reversing radiotherapy resistance in HCC. CTSC expression was significantly higher in HCC tissues than in adjacent non-tumour tissues. Correlation analysis showed that positive CTSC expression was positively associated with aggressive clinicopathological features, including increased tumour number, large tumour size, absence of tumour encapsulation, microvascular invasion and advanced TNM stage. Survival analysis further revealed that CTSC overexpression was linked to poorer overall survival (OS) and progression-free survival (PFS) in HCC patients. In vitro experiments demonstrated that CTSC overexpression increased the clonogenic survival rate of Huh7 cells after ionising radiation (IR) and reduced the apoptosis rate. In both subcutaneous and orthotopic liver tumour models, upregulated CTSC expression significantly decreased radiotherapy sensitivity. Clinically, CTSC overexpression was significantly associated with a poor response to radiotherapy. Mechanistically, CTSC promoted the infiltration of myeloid-derived suppressor cells (MDSCs) while reducing CD8⁺ T cell infiltration by upregulating CXCL1 expression. Importantly, the combination of the CTSC inhibitor AZD7986 with radiotherapy significantly improved radiotherapy sensitivity in HCC models. CTSC contributes to radiotherapy resistance in HCC by recruiting MDSCs. The synergistic application of a CTSC inhibitor with radiotherapy represents an effective combinational treatment strategy for CTSC-positive HCC.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71153"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772677","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":"High ALG1 Expression Is Correlated With Poor Prognosis and the Immune Microenvironment in Glioma.","authors":"Shuxiang Li, Yang Xia, Qiang Liu, Xin Qian, Anhong Liu, Jia Wang, Xinyu Wang, Di Zuo, Jing Zhang, Jinhai Ma, Peng Gao","doi":"10.1111/jcmm.71142","DOIUrl":"10.1111/jcmm.71142","url":null,"abstract":"<p><p>Glioma is the most prevalent primary tumour in the central nervous system. This study investigates ALG1 expression in glioma and its clinical significance. Using the TCGA and CGGA databases, a bioinformatics analysis examines ALG1 expression, its prognostic value, and its link to the immune microenvironment. Clinical samples are analysed using RT-qPCR, Western blotting, and immunohistochemistry/fluorescence for expression validation. Single-cell RNA sequencing (scRNA-seq) assesses ALG1's role in cell state transitions. In vitro, wound healing assays are performed after ALG1 knockdown with siRNA, and in vivo analysis uses an in situ mouse model. The pan-cancer analysis revealed that ALG1 is significantly overexpressed in varioustumours, including glioblastoma (GBM), and is linked to poor patient outcomes. A prognostic nomogram based on ALG1 levels accurately predicted 1-, 3-, and 5-year survival rates for glioma patients. In clinical samples, ALG1 was highly expressed at both mRNA and protein levels, correlating with tumour grade. Single-cell analysis showed increasing ALG1 expression from non-tumorigenic to malignant states, especially in malignant cells. ALG1 overexpression altered tumour microenvironmentsignalling, changing IL10 and CYPA pathways associated with immune suppression. Knocking down ALG1 significantly reduced glioma cell migration and downregulated EMT-related proteins like N-cadherin, β-catenin, and Vimentin. This study highlights ALG1 as a key prognostic biomarker and therapeutic target for glioma, promoting malignancy through increased cell migration, EMT modulation, and an altered immunosuppressive microenvironment.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71142"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722511","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":"Pathogenesis of Adenomyosis: An Integrated Review of Cellular Origins, Molecular Mechanisms, and Intersecting Diseases.","authors":"Jiang Yang, Xiaochong Li, Yu Peng, Zhongfeng Sun, Lingli Zhang, Jie Duan, Nanbert Zhong","doi":"10.1111/jcmm.71129","DOIUrl":"10.1111/jcmm.71129","url":null,"abstract":"<p><p>Adenomyosis is a prevalent disorder of the archimetra, historically conflated with endometriosis but possessing a unique pathobiological trajectory. This review synthesises current molecular evidence to propose a unified mechanistic framework initiated by tissue injury and repair (TIAR), aberrant stem cell activation, or de novo metaplasia, all of which converge to disrupt the endometrial-myometrial interface disruption (EMID). Following this structural breach, a self-perpetuating 'vicious cycle' is triggered, driven by four interconnected axes: (1) Hormonal Dysregulation, characterised by local hyper-estrogenism, progesterone resistance, and a specific paracrine prolactin loop that drives reactive myometrial hypertrophy; (2) Immune-Hemostatic Crosstalk, where activated platelets and M2-polarised macrophages establish a pro-fibrotic niche via TGF-β1 signalling; (3) Hypoxia and Neuroangiogenesis, where HIF-1α stabilisation orchestrates metabolic reprogramming (Warburg effect) and the pathological sprouting of sensory nerves, underpinning chronic pain; and (4) Epigenetic Fibrosis, driven by the oestrogen-slug-VEGF axis and HDAC-mediated chromatin remodelling leading to epithelial-mesenchymal transition (EMT). Furthermore, we clarify the genetic distinction between adenomyosis and uterine leiomyomas, highlighting their divergent responses to androgen receptor signalling. By elucidating these molecular targets, we discuss emerging non-hormonal therapeutics-including anti-platelet agents and dopamine agonists-offering mechanism-based strategies for fertility preservation.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 7","pages":"e71129"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673704","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":"Targeting C/EBPβ to Suppress Myocardial Fibrosis in Hypertensive Heart Disease: Role of the ACE2/Ang-(1-7) Pathway.","authors":"Yuanyuan Tie, Zehao Lin, Ming Zhang, Bincheng Ren, Donggang Han, Kexin Li, Ping Jin, Dengfeng Gao","doi":"10.1111/jcmm.71139","DOIUrl":"10.1111/jcmm.71139","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Hypertensive heart disease is characterised by ventricular remodelling and interstitial fibrosis, in which dysregulation of the renin-angiotensin system (RAS) plays a pivotal role. This study investigated whether the transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) attenuates hypertensive myocardial fibrosis and remodelling by modulating the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)] axis. Eight-week-old male spontaneously hypertensive rats (SHR) received tail-vein injection of lentiviral vectors encoding C/EBPβ, C/EBPβ short hairpin RNA (shRNA), or negative control (n = 6 per group), whereas Wistar-Kyoto rats injected with saline served as normotensive controls. Twelve weeks after injection, blood pressure and echocardiographic parameters were assessed, and cardiac hypertrophy and fibrosis were evaluated by heart weight, heart weight-to-body weight ratio, histology, Masson's trichrome staining with quantitative morphometry, immunohistochemistry and Western blotting. Angiotensin II (Ang II) and Ang-(1-7) levels were quantified in serum and myocardium, and circulating matrix metalloproteinase (MMP)-2/9, interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). In parallel, primary rat cardiac fibroblasts were stimulated with Ang II and treated with lentiviral C/EBPβ overexpression in combination with ACE2-specific or control small interfering RNA (siRNA) to examine ACE2-dependent regulation of collagen I synthesis. C/EBPβ expression was markedly reduced in SHR myocardium compared with normotensive rats. C/EBPβ overexpression lowered arterial pressure, improved systolic and diastolic indices, and attenuated left ventricular hypertrophy and cardiomyocyte enlargement. Myocardial fibrosis was reduced, as shown by a smaller collagen-positive area on Masson's trichrome staining and decreased collagen I, collagen III and transforming growth factor-β1 (TGF-β1) expression. C/EBPβ overexpression shifted the renin-angiotensin system toward the ACE2/Ang-(1-7) axis, with higher ACE2 and Ang-(1-7), lower angiotensin-converting enzyme (ACE) and Ang II, and reduced IL-6 and MCP-1 levels, whereas MMP activity remained largely unchanged. In Ang II-stimulated cardiac fibroblasts, C/EBPβ upregulated ACE2 and suppressed collagen I, while ACE2 knockdown abolished these antifibrotic effects, supporting an ACE2-dependent mechanism. In contrast, C/EBPβ knockdown in vivo had no significant impact on cardiac function, remodelling, fibrosis, inflammation, or RAS components. Myocardial C/EBPβ expression is reduced in hypertensive rats, and its restoration markedly limits hypertension-induced cardiac injury. C/EBPβ overexpression lowers blood pressure, improves systolic and diastolic function and attenuates left ventricular hypertrophy, fibrosis and inflammation. These benefits are associated with a shift from the ACE/Ang II towards the ACE2/Ang-(1-7) axis and reduce","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 7","pages":"e71139"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645483","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":"Cycloastragenol Inhibits Colorectal Cancer Cell Metastasis via Epithelial-Mesenchymal Transition and the PI3K Signalling Pathway.","authors":"JingRong Miao, PanFeng Feng","doi":"10.1111/jcmm.71128","DOIUrl":"10.1111/jcmm.71128","url":null,"abstract":"<p><p>Metastasis remains a critical factor contributing to the low survival rates in colorectal cancer. The pathways through which cycloastragenol suppresses colorectal cancer metastasis are poorly defined. This research directly investigates its anti-metastatic mechanisms. The anti-proliferative effects of cycloastragenol were assessed using CCK-8 assays, while its impact on migration, invasion and apoptosis was evaluated via Transwell assays and flow cytometry. Analysis of protein expression was performed using Western blotting and immunofluorescence. Network pharmacology and molecular docking were employed to predict potential signalling pathways and binding interactions. Additionally, the establishment of an in vivo xenograft mice model enabled us to further validate the antitumour efficacy and mechanistic role of cycloastragenol. Cycloastragenol exhibited a dose- and time-dependent suppression of colorectal cancer cell proliferation. Meanwhile, it inhibits proliferation and migration and promotes apoptosis in a concentration-dependent manner. Cycloastragenol suppresses the activation of the EMT process. Based on an integrated network pharmacology and molecular docking approach, the PI3K/Akt signalling axis emerged as the foremost candidate mechanism. Cycloastragenol exhibits strong binding affinities with PI3K (interaction sites: ARG4, LYS720) and AKT (interaction sites: TYR18, LEU295), with binding energies of -9.0 kcal/mol and -9.3 kcal/mol, respectively. A marked suppression of tumour growth and metastasis was observed in xenograft models following cycloastragenol treatment. The antitumour efficacy of cycloastragenol is mediated primarily through the suppression of the PI3K/AKT signalling pathway, thereby suppressing EMT and impeding CRC progression. These findings provide a preclinical foundation for the potential clinical application of cycloastragenol in CRC therapy.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71128"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699008","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":"Inhibited Differentiation and Growth of Myocyte Associated With Sarcopenia: The Key Role of the lncRNA A430093F15Rik/microRNA-337-3p/Fam168a Pathway.","authors":"Qing Fang, Jianwei Huang, Dongping Huang, Zhenyi Jia","doi":"10.1111/jcmm.71133","DOIUrl":"10.1111/jcmm.71133","url":null,"abstract":"<p><p>Sarcopenia is a muscle disorder characterized by progressive loss of muscle mass, strength and function with ageing. Non-coding RNAs have been reported to be involved in the progression of sarcopenia. The current study aimed to investigate the pathogenesis of sarcopenia. Based on the bioinformatics analyses and RT-qPCR validation, the lncRNA A430093F15Rik was selected as the potential target involved in sarcopenia progression. Its expression level was up-regulated with ageing in mice but down-regulated with myogenesis in C2C12 cells. Modulating A430093F15Rik showed that the inhibition of the lncRNA contributed to the attenuation of sarcopenia such as increased cell viability and enhanced myogenesis, while the overexpression promoted disease progression. The downstream effector of A430093F15Rik, miR-337-3p, showed opposite function to the lncRNA, while Fam168a showed similar effects. Moreover, modulating both factors also confirmed their distinct roles during sarcopenia progression. The dual luciferase and RNA pulldown assays then verified the direct binding between A430093F15Rik and miR-337-3p, and miR-337-3p and Fam168a, representing a ceRNA regulatory mechanism between A430093F15Rik, miR-337-3p and Fam168a. The current study identified a novel lncRNA, A430093F15Rik, that is involved in the progression of sarcopenia by acting as a competitive endogenous RNA (ceRNA) to sponge miR-337-3p and regulate the expression of Fam168a.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71133"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690378","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":"HBx Induces the Production of N-GPC3 in Hepatoma Cells to Promote the Evasion of Macrophage Phagocytosis Through Activating Furin.","authors":"Jiaying Wu, Hongjiu Yu, Yuli Zhou, Yaoquan Lin, Kaiqi Zhang, Wei Li, Zhongzheng Liu, Mengsen Li, Lianghui Gao","doi":"10.1111/jcmm.71122","DOIUrl":"10.1111/jcmm.71122","url":null,"abstract":"<p><p>The hepatitis B virus X protein (HBx) is a central oncogenic driver in hepatocellular carcinoma (HCC). Although glypican-3 (GPC3) is a phosphatidylinositol proteoglycan-specific biomarker for HCC. However, the combined role of HBx and GPC3 in mediating HCC cell evasion from macrophage phagocytosis remains unclear. Here, we demonstrate that HBx modulates macrophage phagocytosis by regulating GPC3 membrane morphology. Analysis of tissues from 30 patients with hepatocellular carcinoma revealed concomitant upregulation of HBx and GPC3 in tumour specimens. Mechanistically, HBx alters ERK site phosphorylation, thereby influencing the enzymatic activity of Furin protease-which cleaves GPC3-and consequently orchestrating morphological changes of membrane-associated GPC3. To functionally validate this, THP-1 cells were polarized to M1 macrophages and co-cultured with HCC cells. Notably, HBx directly impaired macrophage phagocytosis of HCC cells, an effect mediated through GPC3 morphological dynamics. Collectively, these findings indicate that HBx suppresses macrophage phagocytosis of HCC cells by remodelling membrane-associated GPC3.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 7","pages":"e71122"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645494","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 C3aR1 Mediates Sepsis-Induced Myocardial Injury by Triggering Neutrophil Necroptosis.","authors":"Jianbo Xu, Zhilei He, Rubing Zhang, Chaonan Peng, Ziteng Cai, Xinyue Zhao, Weiqun Wang","doi":"10.1111/jcmm.71145","DOIUrl":"10.1111/jcmm.71145","url":null,"abstract":"<p><p>Sepsis-induced myocardial injury (SIMI) is a leading cause of mortality in critically ill patients, driven by dysregulated immune-inflammation responses. Although macrophages and neutrophils are key players in this process, the mechanisms governing their crosstalk in SIMI remain unclear. Here, we demonstrate that the complement C3a receptor 1 (C3aR1) critically mediates this interaction. Using a cecal ligation and puncture (CLP)-induced SIMI rat model and an in vitro co-culture system with THP-1-derived macrophages, HL-60 cells and AC16 cardiomyocytes, we show that C3aR1 promotes macrophage M1 polarisation via the TLR4/NF-κB pathway. The activated M1 macrophages subsequently trigger neutrophil necroptosis, leading to the release of chemokines and establishing a self-amplifying inflammatory loop from M1 polarisation to neutrophil necroptosis and cardiomyocyte injury, ultimately resulting in cardiac dysfunction. Cardiac-specific knockdown of C3aR1 in vivo attenuated myocardial damage, reduced inflammatory cell infiltration and improved cardiac function. Our findings identify C3aR1 as a key molecular hub orchestrating macrophage-neutrophil crosstalk in SIMI and highlight its potential as a therapeutic target for mitigating sepsis-induced cardiac complications.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71145"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722639","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}