JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"From Periodontal Pocket to Systemic Diseases: Mechanistic Insights Into the Role of Porphyromonas gingivalis in Host Pathology","authors":"Alaa Ahmed Basalim,&nbsp;Emily Ming-Chieh Lu","doi":"10.1111/jcmm.71327","DOIUrl":"10.1111/jcmm.71327","url":null,"abstract":"<p><i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), a keystone pathogen in periodontitis, has been increasingly recognised as a mechanistic bridge linking periodontal infection to pathological destruction in distant organs. <i>P. gingivalis</i> virulence factors, including gingipains, lipopolysaccharides (LPS), and outer membrane vesicles (OMVs), mediate complex host–pathogen interactions. In this review, we critically evaluated recent experimental studies which demonstrate the effects of <i>P. gingivalis</i> oral infection on systemic diseases, including cardiovascular disease (CVD), diabetes mellitus (DM), adverse pregnancy outcomes (APOs), colorectal cancer (CRC), and Alzheimer's disease (AD). In CVD, DM, and AD, <i>P. gingivalis</i> gingipains exert proteolytic activity that disrupts key cellular targets, including endothelial adhesion molecules, insulin receptors in insulin-responsive tissues, and neuronal proteins. In AD, <i>P. gingivalis</i> LPS contributes to neuronal damage by inducing tau hyperphosphorylation and synaptic dysfunction. In APO and AD, <i>P. gingivalis</i> OMVs play a central role in compromising barrier integrity. These processes converge on five principal pathogenic pathways: (1) barrier and structural disruption, (2) immune activation and subversion, (3) mitochondrial dysfunction and oxidative stress induction, (4) systemic inflammation, and (5) metabolism-mediated effects. Understanding these shared pathways underscores the importance of controlling periodontal disease in promoting systemic health.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828558","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":"PACS2 at Mitochondria-Associated Membranes: A Central Regulator of Cardiovascular and Metabolic Diseases","authors":"Baiyi Tang,&nbsp;Hui Wang,&nbsp;Jie Ouyang","doi":"10.1111/jcmm.71336","DOIUrl":"10.1111/jcmm.71336","url":null,"abstract":"<p>Cardiovascular and metabolic diseases (CVMDs), which are characterized by metabolic dysregulation and cardiovascular impairment, constitute a major global cause of mortality, thus highlighting the urgent need for novel therapeutic strategies. Phosphofurin acidic cluster sorting protein 2 (PACS2), a multifunctional adapter protein localized to mitochondria-associated membranes (MAMs), regulates intracellular membrane trafficking and is pivotal for critical cellular processes, including apoptosis, autophagy and ferroptosis. Accumulating evidence implicates PACS2 dysregulation in the pathogenesis of diverse CVMDs, including metabolic disorders and cardiovascular conditions. This review examines the structural and functional basis of PACS2 and details its established and emerging roles in the pathogenesis of CVMDs. Collectively, these findings identify PACS2 as a crucial regulator of CVMD development and progression, underscoring its significant potential as both a diagnostic biomarker and a promising therapeutic target.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818493","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":"Quantitative and Targeted Regulation of Ferroptosis in Bladder Cancer: Preclinical Study","authors":"Ying Dong,&nbsp;Chaojie Xu,&nbsp;Bing Yan,&nbsp;Shuanzhu Mou,&nbsp;Chen Li,&nbsp;Yuchen Liu","doi":"10.1111/jcmm.71333","DOIUrl":"10.1111/jcmm.71333","url":null,"abstract":"<p>The activation of ferroptosis, a cell death mechanism driven by excessive ferrous ions (Fe²⁺) and lipid peroxides, has emerged as a promising target for cancer treatment. However, in the case of quantitative regulation of target genes, it remains uncertain whether ferroptosis can be induced in bladder cancer (BCa) cells without affecting normal ones. We investigated this using an innovative CRISPR-dCas9 system to upregulate and downregulate the ferroptosis-related gene BECN1 and OTUB1, respectively. We identified two genes that can affect and promote ferroptosis-related pathways, analysing their expression in bladder tissue through The Cancer Genome Atlas. Our unique CRISPR-dCas9 technology, under the control of an hTERT promoter, selectively adjusted BECN1 and OTUB1 expression exclusively in cancer cells. RT-qPCR and western blotting demonstrated significant alterations in the expression of GPX4 and SLC7A11, proteins strongly associated with ferroptosis, in BCa cells, while normal bladder cells remained unaffected. We developed a quantitative model based on synthetic biology principles to describe the regulatory relationships between the ferroptosis-related genes BECN1 and OTUB1 and their downstream targets GPX4 and SLC7A11 in bladder cancer cells. The model establishes a direct proportional relationship between BECN1 upregulation and decreased GPX4 expression, and between OTUB1 downregulation and decreased SLC7A11 expression. In vitro experiments revealed reduced viability, proliferation, migration, and invasion in UMUC-3 and T24 BCa cells. Importantly, Fer-1 and DFO rescued the viability loss, and C11-BODIPY staining confirmed increased lipid ROS accumulation, supporting ferroptosis-associated cell death following BECN1/OTUB1 regulation. In vivo xenograft experiments showed that BECN1 upregulation or OTUB1 downregulation suppressed tumour growth. Tumour-tissue immunofluorescence further showed reduced GPX4 expression in BECN1-upregulated tumours and reduced SLC7A11 expression in OTUB1-downregulated tumours, supporting suppression of the GPX4/SLC7A11 ferroptosis-protective axis in vivo. The quantitative equation derived from our data suggests that the induction of ferroptosis in bladder cancer cells can be effectively modulated by these two genes, and the experimental results also indicate our system can modulate these two genes to affect the function of BCa cells without affecting the normal cells, offering a promising new direction for the development of targeted therapy for bladder cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818566","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":"Loss-of-Function Mutations in SWI/SNF Complexes Associated With Active Tumour Immune Microenvironment Clinical Response to Immune Checkpoint Blockade","authors":"Zheng Yang,&nbsp;Zixuan Tian,&nbsp;Renji Liang,&nbsp;Yi Lu,&nbsp;Tengfei Zhu,&nbsp;Ya-nan Wang,&nbsp;Wei Zhang","doi":"10.1111/jcmm.71290","DOIUrl":"10.1111/jcmm.71290","url":null,"abstract":"<p>Chromatin remodelling SWI/SNF complexes are recurrently altered in malignancies, and some members were found to be associated with immune checkpoint blockade (ICB) response. However, it is unclear whether SWI/SNF complex genes as a collective factor have clinical relevance. Through pan-cancer analysis of 8507 tumours across 26 types from The Cancer Genome Atlas, we demonstrate that SWI/SNF loss-of-function (LOF) mutations correlate with elevated immunogenicity markers, such as higher tumour mutational burden (TMB), neoantigen load, and microsatellite instability. SWI/SNF-LOF tumours exhibited enriched CD8⁺ T cell and M1-like macrophage infiltration, upregulation of major histocompatibility complex class genes, and increased expression of immunostimulators, immunoinhibitors, and chemokines. Crucially, in ICB-treated patients across discovery (<i>n</i> = 750) and validation (<i>n</i> = 562) cohorts encompassing nine cancer types, SWI/SNF-LOF status consistently predicted superior clinical outcomes, including prolonged overall survival, progression-free survival, and higher objective response rates compared to non-mutated tumours. Multivariate analysis confirmed SWI/SNF-LOF as an independent ICB response predictor independent of TMB, age, sex, or cancer type. These findings identify SWI/SNF LOF mutations as promising biomarkers of an inflamed tumour microenvironment and favourable responses to ICB across multiple solid tumours.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818431","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":"RETRACTION: Salvianolic Acid B-Induced MicroRNA-152 Inhibits Liver Fibrosis by Attenuating DNMT1-Mediated Patched1 Methylation","authors":"","doi":"10.1111/jcmm.71335","DOIUrl":"10.1111/jcmm.71335","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>F. Yu</span>, <span>Z. Lu</span>, <span>B. Chen</span>, <span>X. Wu</span>, <span>P. Dong</span>, and <span>J. Zheng</span>, “ <span>Salvianolic Acid B-Induced MicroRNA-152 Inhibits Liver Fibrosis by Attenuating DNMT1-Mediated Patched1 Methylation</span>,” <i>Journal of Cellular and Molecular Medicine</i> <span>19</span>, no. <span>11</span> (<span>2015</span>): <span>2617</span>–<span>2632</span>, https://doi.org/10.1111/jcmm.12655.\u0000 </p><p>The above article, published online on 10 August 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Specifically, the GAPDH blot shown in Figure 1D was found to have been later published elsewhere by the same author group but presented in a different scientific context. Further investigation by the publisher identified additional concerns, namely that the GAPDH bands in Figures 3C and 5B had been previously published by a different author group in a different scientific context.</p><p>The clarification and materials provided by the authors were insufficient to address these concerns, and the authors did not supply the original data underlying the study upon request. Accordingly, the article has been retracted, as the editors consider its conclusions to be invalid. The authors have been informed of the retraction decision but were not available for final confirmation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813013","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":"Epigenetic Activation of the KDM6B-DKK1 Axis Promotes Colorectal Cancer Peritoneal Metastasis Through Wnt/β-Catenin-Associated EMT","authors":"Zhichao Zhai,&nbsp;Jiajia Chen,&nbsp;Yong Yang,&nbsp;Ming Li","doi":"10.1111/jcmm.71326","DOIUrl":"10.1111/jcmm.71326","url":null,"abstract":"<p>Peritoneal metastasis (PM) is a highly lethal pattern of progression in colorectal cancer (CRC), yet the specific molecular drivers and upstream regulatory mechanisms underlying this process remain incompletely understood. In the present study, public transcriptomic datasets from TCGA and GEO were integrated to identify PM-associated genes in CRC, and prognostic relevance was evaluated using Kaplan–Meier survival analysis and Cox regression. Stable knockdown and overexpression models were established to investigate the role of DKK1 in CRC cell migration, invasion and peritoneal dissemination using Transwell assays and a mouse peritoneal metastasis model. Multi-cohort analysis identified 86 genes specifically upregulated in PM, among which DKK1 showed the most consistent overexpression and was significantly associated with poor prognosis in patients with CRC. Functionally, DKK1 knockdown significantly suppressed CRC cell migration, invasion and peritoneal metastatic colonization in vivo, whereas DKK1 overexpression enhanced these malignant phenotypes. Mechanistically, DKK1 promoted metastasis in association with activation of the Wnt/β-catenin signalling programme and induction of epithelial-mesenchymal transition. Upstream analysis demonstrated that the histone demethylase KDM6B was positively correlated with DKK1 expression and directly activated DKK1 transcription by binding to its promoter and reducing H3K27me3 enrichment. Rescue experiments further indicated that the pro-metastatic and epithelial-mesenchymal transition-promoting effects of KDM6B were largely dependent on DKK1. Collectively, these findings identify DKK1 as a key driver of CRC PM and establish the KDM6B-DKK1-Wnt/β-catenin-epithelial-mesenchymal transition axis as a critical regulatory pathway in this process.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808703","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":"Emetine and Its Derivatives as Anticancer Agents Targeting the PI3K/AKT/mTOR Pathway: A Narrative Review of Mechanisms, Pharmacology, and Clinical Insights","authors":"Mst. Ismatara Khatun,&nbsp;Samy Selim,&nbsp;Asif Hassan Malik,&nbsp;Md. Sakib Al Hasan,&nbsp;Abul Bashar Ripon Khalipha,&nbsp;Noshin Tasnim Yana,&nbsp;Mohammad Y. Alshahrani,&nbsp;Md. Arif Hossain,&nbsp;Imam Hossen Rakib,&nbsp;Anike Chakrabarty,&nbsp;Emon Mia","doi":"10.1111/jcmm.71328","DOIUrl":"10.1111/jcmm.71328","url":null,"abstract":"<p>Emetine (EMT), a naturally occurring tetrahydroisoquinoline alkaloid, shows diverse biological actions, including anticancer effects. Despite existing studies, the role of EMT derivatives in cancer, particularly in relation to the PI3K/AKT/mTOR signalling pathway, remains largely underexplored. This review explores the potential of EMT in targeting PI3K/AKT/mTOR molecular pathways across different cancer types. Data were collected from reliable and well-established sources, including PubMed, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings showed that EMT derivatives suppress PI3K-AKT-mTOR pathway activity in multiple cancers such as liver, gastric, acute myeloid leukaemia (AML), and brain, with IC₅₀ values ranging from 0.0244 to 1 μM. Beyond its anticancer activity, EMT showed broad pharmacological relevance, including antiviral, antiparasitic, and contraceptive activities. Preclinical assessments suggest preferential cytotoxicity toward cancer cells at low concentrations; however, known dose-dependent adverse effects, including cardiotoxicity and emetic responses at higher doses, necessitate careful dose optimization before clinical translation. Clinical evidence remains insufficient, and EMT should be considered a preclinically active compound warranting further rigorous translational investigation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808657","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":"Identification and Experimental Validation of Key Genes Related to Neuroendocrine in Periodontitis Based on Single-Cell and Bulk Transcriptome Data","authors":"Jiaguan Zhang,&nbsp;Ziyan Liu,&nbsp;Jianqing Deng,&nbsp;Peishan Huang,&nbsp;Huijuan Liu","doi":"10.1111/jcmm.71329","DOIUrl":"10.1111/jcmm.71329","url":null,"abstract":"<p>Periodontitis is a chronic inflammatory condition linked to systemic diseases, yet the neuroendocrine mechanisms underlying its pathogenesis remain unclear. This study aimed to elucidate neuroendocrine-related molecular pathways involved in periodontitis. Transcriptomic data and neuroendocrine-related genes (NRGs) were integrated to identify candidate genes from the overlap between differentially expressed genes (DEGs) and NRGs. Machine learning, ROC analysis and expression validation were used to screen key genes and construct a diagnostic nomogram. Functional enrichment, immune infiltration, drug prediction, molecular docking and single-cell analyses were performed. Key gene expression was further validated using clinical samples. Nine candidate genes were obtained from the intersection of 210 DEGs and 1441 NRGs. Five key genes—FOXN1, XBP1, HCLS1, IRF4 and RORA—were identified and used to develop an effective diagnostic model. These genes showed distinct tissue and cellular distributions and were enriched in pathways such as Ribosome and Protein processing in the ER. Sixteen immune cell types differed between groups, and 24 potential drugs, including melatonin, were predicted. Single-cell analysis highlighted T cells and Endothelial cells as central cell populations. PCR results aligned with bioinformatic findings. Five neuroendocrine-related genes were identified as potential diagnostic biomarkers and therapeutic targets, offering new insights into the neuroendocrine mechanisms of periodontitis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808654","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":"Genome-Wide Assessment of DNA Methylation Fidelity Identifies Representative Ovarian Cancer Cell Line Models","authors":"Asia Jordan,&nbsp;Abby Caffrey,&nbsp;Carson Stacy,&nbsp;Ruby Yun-Ju Huang,&nbsp;Tuan Zea Tan,&nbsp;Aideen McCabe,&nbsp;Kellie Dean,&nbsp;Sudipto Das,&nbsp;Antoinette S. Perry","doi":"10.1111/jcmm.71334","DOIUrl":"https://doi.org/10.1111/jcmm.71334","url":null,"abstract":"<p>Epithelial ovarian cancer comprises multiple distinct histotypes with different molecular, clinical, and therapeutic characteristics, yet ovarian cancer cell lines are often broadly classified as ‘ovarian carcinoma’ or ungraded ‘serous’. While studies have classified cell lines using mutations, transcriptomics, or immunophenotypes, their DNA methylation profiles remain poorly characterised. Given the role of DNA methylation in epithelial ovarian cancer, histotype-specific methylation profiling is essential to determine how accurately cell lines model primary tumours and to guide their appropriate use. The Infinium 450 K and EPIC DNA methylation profiles of 60 unique ovarian cancer cell lines and 108 ovarian tumours were evaluated though a correlation and effect size analysis, focusing on genetic and epigenetic domains. DNA methylation patterns were found to be highly conserved between cell lines and tumour tissues at key transcriptional regulatory domains (CpG islands, shores, and 5′ regulatory regions), with these CpG-dense loci more accurately reflecting in vivo conditions than CpG-sparse regions. We identified specific cell lines with representative epigenetic signatures of high-grade serous, clear cell, endometrioid, mucinous and mixed ovarian carcinoma histotypes. This study provides a framework to optimise the selection and application of ovarian cancer cell line models in DNA methylation research.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785222","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":"Corylin Confers Vasoprotection via JDP2-Nrf2 Antioxidant Axis against Chronic Kidney Disease-Induced Smooth Muscle Cell Remodelling","authors":"Shang-En Huang,&nbsp;Chih-Le Lin,&nbsp;Kazunari K. Yokoyama,&nbsp;Kai-Fang Hu,&nbsp;Bin-Nan Wu,&nbsp;Zen-Kong Dai,&nbsp;Meng-Xuan Lin,&nbsp;Yu-Hsin Tseng,&nbsp;Jong-Hau Hsu,&nbsp;Jwu-Lai Yeh","doi":"10.1111/jcmm.71331","DOIUrl":"https://doi.org/10.1111/jcmm.71331","url":null,"abstract":"<p>Vascular calcification is a pathological process involving vascular smooth muscle cells (VSMCs) phenotypic switching into osteoblast-like cells within a calcium phosphate-deposited environment. This transformation is a critical risk factor for cardiovascular morbidity and mortality in patients with hyperphosphatemia due to chronic kidney disease. Corylin, a major compound derived from the Chinese medicine herb <i>Psoralea corylifolia</i>, is beneficial for the cardiovascular system. However, its role in modulating VSMC phenotypic switching and calcification remains to be elucidated. A vascular calcification rat model induced by vitamin D3 plus nicotine (VDN) was established to evaluate the therapeutic effects of corylin. The protective effects of corylin were evaluated in high phosphate-induced vessels and VSMCs using cytotoxicity assay, Alizarin red S staining, alkaline phosphatase staining, immunofluorescence, Western blot analysis, and qPCR. The interaction between Jun dimerisation protein 2 (JDP2) and Nrf2 was analysed using a ChIP-qPCR assay. Corylin treatment ameliorated arteriosclerotic lesions and oxidative stress in rats treated with VDN. We also observed that the cytoprotective effects of corylin prevented VSMC apoptosis and deposition of calcium phosphates. Additionally, corylin decreased calcium overload by inhibiting calcineurin and maintaining mitochondrial homeostasis. We identified a robust co-induction of JDP2 and Nrf2 in corylin-treated VSMCs, which contributed to reducing phenotypic switching and abrogating oxidative stress. Furthermore, Nrf2 knockdown by an inhibitor abolished JDP2 activation and the protective effects of corylin. Our study reveals that corylin exerts anti-arteriosclerotic and vasculoprotective effects targeting JDP2-Nrf2 activation, making it a potential treatment for vascular calcification.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784950","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}