Genetics research最新文献

{"title":"Exploring Deleterious Nonsynonymous SNPs in the <i>ACADM</i> Gene: Insights Into Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) via In Silico Analysis.","authors":"Muhammad Waleed Iqbal, Muhammad Shahab, Fakhreldeen Dabiellil, Yousef A Bin Jardan, Mohammed Bourhia, Xinxiao Sun, Qipeng Yuan","doi":"10.1155/genr/6682668","DOIUrl":"10.1155/genr/6682668","url":null,"abstract":"<p><p>Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), a potentially lethal metabolic disorder, is often associated with single-nucleotide polymorphisms (SNPs) in the acyl-CoA dehydrogenase, medium-chain (<i>ACADM</i>) gene. The current research investigates the structural and functional implications of these genetic variants through diverse bioinformatics techniques. A range of in silico techniques were utilized to thoroughly evaluate the effect of nonsynonymous SNPs. Molecular docking and molecular dynamics simulation evaluation comprehensively validated the mutational impact on protein's stability. Gene interaction analysis demonstrated that <i>ACADM</i> is involved in several cellular pathways and co-expression networks. Two nsSNPs, rs121434282 and rs200724875, were found to have a significant impact on the composition and functionality of <i>ACADM</i>. This research lays the foundation for precision medicine advancements, specifically against metabolic disorders. Thorough validation of the proposed nsSNPs, supported by animal models, is crucial for understanding their role in MCADD.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"6682668"},"PeriodicalIF":2.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diverse Roles of the Histone-Like Nucleoid Structuring (H-NS) Protein in <i>Vibrio parahaemolyticus</i>.","authors":"Hao Tang, Yiquan Zhang","doi":"10.1155/genr/6503207","DOIUrl":"10.1155/genr/6503207","url":null,"abstract":"<p><p>The histone-like nucleoid structuring (H-NS) protein is a global transcriptional regulator critical for bacterial genome organization and gene expression. In <i>Vibrio parahaemolyticus</i>, H-NS represses virulence factors such as thermostable direct hemolysin (TDH), type III secretion systems (T3SS1/T3SS2), and type VI secretion systems (T6SS1/T6SS2). It also modulates swimming motility by activating polar flagellar genes while repressing swarming motility and lateral flagellar systems. Additionally, H-NS influences biofilm formation through regulation of exopolysaccharide synthesis and cyclic di-GMP (c-di-GMP) metabolism. Emerging evidence suggests cross-regulation with quorum sensing (QS) systems, though direct mechanistic insights into <i>V. parahaemolyticus</i> remain sparse. Furthermore, a recent study indicates H-NS roles extend to osmotic stress adaptation, such as regulating the ectoine biosynthetic pathway. This review synthesizes current knowledge on H-NS-mediated regulation in <i>V. parahaemolyticus</i> and offers new insights for future research.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"6503207"},"PeriodicalIF":2.1,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis-Related Diagnostic Biomarkers in Non-Neovascular Age-Related Macular Degeneration: An Integrative Transcriptomic and Experimental Study.","authors":"Jiaming Li, Yirong Ma, Miao Hu, Qian Zhang, Anqi Wang, Qiuyu Tang, Qinshang Guo, Binglin Huang","doi":"10.1155/genr/8903808","DOIUrl":"10.1155/genr/8903808","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD), particularly its non-neovascular (dry) form, is a progressive retinal disorder that causes central vision loss and substantial impairment in daily life. Inflammation and immune dysregulation are recognized as core drivers of AMD, yet the contribution of PANoptosis, a form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis, remains unclear. In this study, we integrated human single-cell transcriptomic and bulk microarray datasets from the retina and retinal pigment epithelium-choroid to characterize PANoptosis-related transcriptional changes in dry AMD. Dimensionality reduction, cell-type annotation, and PANoptosis gene-set scoring revealed a distinct PANoptosis signature enriched in AMD, with particularly strong activation in myeloid populations. By combining differential expression analysis with machine learning-based feature selection, we identified four PANoptosis-related genes (PON2, BNIP3, EPHB6, and TPD52) that robustly distinguished AMD from control samples and were associated with an altered immune microenvironment. Genetic instrument analysis further suggested a positive association between TPD52 expression and AMD risk. At the cellular level, our data highlighted macrophages, especially pro-inflammatory M1-like macrophages, as key coordinators of PANoptosis-related pathways in dry AMD. To validate these findings in vivo, we used a sodium iodate-induced mouse model of dry AMD and observed significant dysregulation of PON2, BNIP3, EPHB6, and TPD52 in the retina by RT-qPCR, consistent with the human transcriptomic results and supporting their involvement in retinal degeneration and inflammation. Together, these findings implicate PANoptosis as an important and previously underappreciated component of dry AMD pathophysiology, define a four-gene PANoptosis-related signature with diagnostic potential, and suggest new molecular targets for therapeutic intervention.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"8903808"},"PeriodicalIF":2.1,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Structural Equation Modeling Combined With Post-GWAS Analysis Identifies Two Risk Gene Loci and Functionally Sensitive Genes Associated With Cardiac Conduction Block.","authors":"Tongyu Wang, Xinge Miao, Yunlong Xia","doi":"10.1155/genr/1063531","DOIUrl":"10.1155/genr/1063531","url":null,"abstract":"<p><strong>Background: </strong>Cardiac conduction disorders (CCDs) represent a broad spectrum of severe cardiovascular conditions associated with syncope and sudden cardiac death. Therefore, identification of reliable biomarkers is necessary to significantly improve the diagnostic accuracy and therapeutic outcomes of CCDs. This study analyzed GWAS summary datasets using a genomic structural equation model (Genomic-SEM), fine mapping, linkage disequilibrium score regression (LDSC), and two-sample Mendelian randomization (TSMR) analyses to identify genetic loci and genes associated with CCDs.</p><p><strong>Methods: </strong>GWAS summary datasets of European subjects were obtained from the GWAS Catalog and FinnGen databases. The GenomicSEM R package was used to construct a structural equation model to identify common latent factors influencing CCD progression. The Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA) platform was used to annotate the lead SNPs and candidate genes. Fine-mapping tools, such as SuSiE and FINEMAP, and Phenome-Wide Association Study (PheWAS) analysis were used to identify causal SNPs associated with CCDs. Transcriptome-Wide Association Study (TWAS) and Functional Summary Statistics (FOCUS) analyses were performed to identify CCD susceptibility genes. LDSC and TSMR were performed to determine causal relationships between the candidate risk genes and specific CCDs.</p><p><strong>Results: </strong>Newly explored CCD-associated leading SNPs (rs71208329 and rs112720315) were generated from genomic SEM and FUMA analyses. Fine-mapping and PheWAS analysis confirmed that rs112720315 was linked to nonischemic cardiomyopathy. TWAS, FUMA, and FOCUS analyses showed that five genes (<i>CCDC141</i>, <i>SCN10A</i>, <i>SH3PXD2A</i>, <i>FKBP7</i>, and <i>ESR2</i>) were associated with CCDs. The <i>APOL1</i> gene is associated with the risk of CCDs in African ancestry. TSMR and LDSC analyses further demonstrated that these genes were significantly associated with CCDs and were potential prediction biomarkers for CCDs.</p><p><strong>Conclusion: </strong>The novel genetic locus rs112720315 is significantly associated with the occurrence of CCDs. Biomarkers such as <i>CCDC141</i>, <i>SCN10A</i>, <i>ESR2</i>, <i>FKBP7</i>, <i>and SH3PXD2A</i> can predict a wide spectrum of CCDs. The <i>APOL1</i> gene is a specific marker for CCDs in African ancestry.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"1063531"},"PeriodicalIF":2.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics and Integrated Bioinformatic Analysis Reveal Critical Biomarkers and Immune Infiltration Characteristics in Osteoarthritis.","authors":"Tiantian Gao, Chongshan Yang, Yikang Bi, Pingzhou Zou, Ma Wan, Shenghui Lan, Yuan Song, Yafeng Xu","doi":"10.1155/genr/1174568","DOIUrl":"10.1155/genr/1174568","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a complex, progressive joint disease characterized by cartilage degradation and inflammation. Traditional bulk tissue analyses have limited our understanding of the cellular diversity within OA tissues.</p><p><strong>Methods: </strong>This study employed scRNA-seq and integrated bioinformatic analyses to investigate the cellular composition and molecular pathways involved in OA. Publicly available datasets were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. The genes, such as <i>NR4A2</i>, <i>BMP1</i>, and <i>AVPR1A</i>, were selected for further analysis. Molecular docking studies were conducted to explore the interaction with two identified compounds. Additionally, immune infiltration characteristics were analyzed using gene set variation analysis (GSVA) and correlation with key OA-associated genes.</p><p><strong>Results: </strong>We analyzed cartilage samples from OA and normal individuals (GSE220243) and identified eight distinct chondrocyte subpopulations, with significant pathway enrichment in TNF, TGF-β, and PI3K-Akt signaling pathways. Further differential gene expression analysis of GSE114007 identified 2247 genes, including 26 key OA-associated drug targets, such as <i>NR4A2</i>, <i>BMP1</i>, and <i>AVPR1A</i>, which demonstrated strong diagnostic potential (AUC > 0.70) across multiple cohorts. Immune infiltration analysis revealed significant correlations between these key genes and immune cell subsets, highlighting their roles in the inflammatory microenvironment of OA. Additionally, molecular docking studies suggested that bexarotene has a favorable binding affinity for NR4A2, BMP1, and AVPR1A, making it a promising therapeutic candidate.</p><p><strong>Conclusion: </strong>Our findings provide new insights into the molecular landscape of OA, offering valuable biomarkers and therapeutic targets for future OA interventions.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"1174568"},"PeriodicalIF":2.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation Landscapes of Cartilage in Hip Osteoarthritis.","authors":"Ruiyang Jiang, Maochun Wang, Guihua Tan, Jie Lv, Xiaoyu Jin, Yuan Liu, Rui Wu, Dongquan Shi","doi":"10.1155/genr/5540232","DOIUrl":"10.1155/genr/5540232","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate different methylation landscapes between cartilage of femoral neck fracture and preserved and damaged cartilages in hip osteoarthritis (OA).</p><p><strong>Methods: </strong>Genome-wide DNA methylation data were acquired from two data sets in GEO database (GSE63106 and GSE63695), which were based on Illumina HumanMethylation450 BeadChip arrays. A total of 63 hip samples were selected for further analysis, including 19 cartilages obtained from patients with femoral neck fracture, 14 preserved cartilages, and 30 damaged cartilages obtained from patients with OA. We identified the differential methylated positions (DMPs) and genes between different cartilage groups.</p><p><strong>Results: </strong>There were 116,750 DMPs and 51,200 DMPs identified in preserved and damaged cartilages compared to cartilage in femoral neck fracture, respectively, while there were no signals found between preserved and damaged cartilages. Gene ontology analysis showed that most of differential methylated genes were enriched in extracellular matrix and structure organization, collagen-containing extracellular matrix, and KEGG enrichment highlighted PI3K-AKT and AMPK signaling pathways, which were known to be crucial for the progression of OA. Further construction of protein-protein interaction networks with differential methylated genes elucidated molecular basis of the disease. Three hypermethylated genes (NOTCH1, GREM1, and DYSF) and three hypomethylated genes (HDAC4, S100A10, and RUNX1) were selected to detect the relative expression in different cartilages, and their expression was correlated with the methylation status within the genes.</p><p><strong>Conclusion: </strong>We demonstrated the differential methylated genes across the whole genome not only on preserved cartilage but also on damaged cartilage during OA. The molecular network highlighted the potential therapy targets which may be involved in the initiation or progression of the disease.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 ","pages":"5540232"},"PeriodicalIF":2.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Germline Variants in the DNA Mismatch Repair Genes in Chinese Colorectal Cancer Patients.","authors":"Xiu Zhu, Da Han, Jun Chen, Jingjing Xu, Jiaoyue Jin, Qian Lai, Lina Xie, Jianfei Fang, Liu Zhu, Ying Yu, Jun Yang, Taoli Wang, Xueping Xiang, Xuejiang Shi, Desheng Xiao, Dan Su","doi":"10.1155/genr/9910339","DOIUrl":"10.1155/genr/9910339","url":null,"abstract":"<p><strong>Background: </strong>A multicenter study on the DNA mismatch repair (MMR) genes enabled us to study the profiling of germline variants in MMR genes of colorectal cancer (CRC) patients with MMR deficiency (dMMR). The clinicopathological differences between Lynch syndrome (LS) patients and sporadic dMMR CRC patients were compared by Student's t-test and χ² test. The molecular profiling of germline variants in MMR genes in Chinese CRC patients with dMMR is clarified.</p><p><strong>Methods: </strong>A total of 326 CRC patients with dMMR were enrolled. Next-generation sequencing (NGS) and Sanger sequencing were performed using tumor-adjacent tissues of enrolled patients. Four MMR genes (MLH1, MSH2, MSH6, and PMS2) are included in the NGS panel.</p><p><strong>Results: </strong>A total of 113 germline variants were detected, including 81 pathogenic and likely pathogenic variants. The clinicopathologic differences between CRC patients with/without LS were observed in age, family history, lesion location, and dMMR patterns. The CRC cohort with IHC-MSH6 negative alone shows the highest prevalence rate of LS. MLH1 was detected with the most germline variants. The mutational hotspot region of MLH1 is Exon 8, Exon 4 for MSH6, Exon 11 for PMS2, and Exon 7 for MSH2. Several germline hotspots were labeled on each MMR gene sequence by fixed-size bin analysis. In addition, some variants were novel discovered based on the presence or absence of the RS number and allele frequency record.</p><p><strong>Conclusions: </strong>Our study classified the clinicopathological features between sporadic CRC patients and LS patients. More importantly, the molecular profiling of the MMR gene germline variant was experimentally elucidated, which deepens the knowledge of MMR genes and provides a new perspective for the subsequent studies on the landscape of germline variants of Chinese LS patients.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e9910339"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the rs688 Polymorphism in the Gene Encoding Low-Density Lipoprotein Receptor in Bangladeshi Population With Coronary Artery Disease.","authors":"Imran Hossain, Nahid Sharmin, Istiaque Ahmed, Golam Saklayen, Sauda Sumaya Dina, Sheikh Zahir Raihan","doi":"10.1155/genr/5670428","DOIUrl":"10.1155/genr/5670428","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) is among the leading causes behind the morbidity and mortality of the world population. Among others, low-density lipoprotein (LDL) is one of the main drivers behind the development of CAD, and the LDL receptor (LDLR) plays a central role in cholesterol homeostasis by facilitating the clearance of LDL cholesterol from the blood. The LDLR rs688 single-nucleotide polymorphism in exon 12 has been reported to influence mRNA splicing efficiency, potentially modifying receptor function and lipid metabolism. The aim of this study was to assess the association between LDLR rs688 polymorphism and CAD susceptibility among CAD patients in the Bangladeshi population and to determine its relationship with serum LDL level.</p><p><strong>Methods: </strong>A case-control study was conducted involving 225 participants, including 150 CAD patients and 75 healthy controls. High-density lipoprotein, LDL, triglycerides, and total cholesterol were measured by biochemical tests using appropriate kits. The LDLR genotype was identified using the allele-specific PCR (AS-PCR) technique.</p><p><strong>Results: </strong>Relative to the control group, the CAD group showed a higher distribution frequency of the TT genotype (17.33%) and a lower frequency of the CC genotype (15.33%). The LDLR rs688 TT genotype showed significant association with CAD among Bangladeshi patients (OR = 3.617, 95% CI: 1.089-10.05; p = 0.0352). Furthermore, individuals carrying the TT and CT genotypes exhibited higher LDL levels compared with those carrying the CC genotype (p < 0.05). Finally, univariate and multivariate logistic regression analyses revealed that the LDLR rs688 TT genotype remained significantly associated with CAD after adjustments for covariates (p < 0.05).</p><p><strong>Conclusion: </strong>This hospital-based case-control study provides preliminary evidence of an association between the LDLR rs688 TT genotype and CAD in a Bangladeshi population. These findings are preliminary and require validation in larger, population-based studies.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e5670428"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Subtype Classification and Mechanistic Investigation Based on Ferroptosis-Related lncRNAs in Ovarian Cancer.","authors":"Qianru Li, Mengyao Lv, Aijie Zhang, Xue Liu, Wanting Lu, Min Shao, Limian Cao","doi":"10.1155/genr/4503115","DOIUrl":"10.1155/genr/4503115","url":null,"abstract":"<p><p>Ovarian cancer (OC) ranks among the most prevalent malignant tumors in women, contributing significantly to mortality rates. This disease exhibits considerable heterogeneity, characterized by intricate molecular and genetic alterations. Ferroptosis, a distinct form of cell death, has emerged as a critical factor in various cancers, including OC. However, the regulatory mechanisms underlying ferroptosis in OC patients remain unclear and require further investigation. This study aimed to identify lncRNA associated with OC and elucidate the underlying mechanisms through bioinformatics methods and experimental validation. Ferroptosis-related lncRNAs (FRLs) was identified in OC, and its prognostic value was assessed using univariate Cox analysis. Additionally, the molecular subtypes of FRLs were evaluated through the ConsensusClusterPlus software package. Notably, Cluster 2 exhibited a low TME score, which was linked to a poorer prognosis. The GSEA suggested that Cluster 2 shared similarities with other clusters associated with worse survival outcomes, likely due to the activation of tumor-associated pathways. In vitro experiments further confirmed that certain lncRNAs could be upregulated under ferroptotic conditions. We focused on two lncRNAs, AC027348.1 and TRAM2-AS1, which were not noticed before and were significantly upregulated, to explore their regulatory effects on ferroptosis. The underlying mechanisms were preliminarily investigated through transcriptome sequencing. In summary, our findings offer new insights into the pathogenesis of OC, particularly regarding the role of lncRNAs related to ferroptosis.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e4503115"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STOML2 Alleviates Osteoarthritis by Regulating Mitochondrial Energy Metabolism and Oxidative Stress.","authors":"Fei Xie, Kun Miao, Hao Wu, Xuejun Wu","doi":"10.1155/genr/9303825","DOIUrl":"10.1155/genr/9303825","url":null,"abstract":"<p><p>Osteoarthritis (OA) is associated with chondrocyte dysfunction and cartilage degeneration, but how mitochondrial homeostasis is maintained during OA progression remains incompletely understood. Here, we show that Stomatin-like protein 2 (STOML2) is downregulated in IL-1β-stimulated chondrocytes and in human OA cartilage. STOML2 depletion impairs oxidative phosphorylation, elevates mitochondrial reactive oxygen species, and promotes chondrocyte senescence and ferroptotic cell death. Mechanistically, STOML2 interacts with the mitochondrial Na⁺/Ca²⁺ exchanger (NCLX) to support mitochondrial Ca²⁺ efflux and metabolic stability. Restoring STOML2 enhances NCLX-dependent Ca²⁺ handling, mitigates mitochondrial Ca²⁺ overload and the glycolytic shift, and improves ATP production. In a rat OA model, intra-articular delivery of STOML2 attenuates cartilage degeneration and reduces inflammatory changes in the joint. Together, these findings identify a STOML2-NCLX axis that safeguards mitochondrial Ca²⁺ homeostasis and chondrocyte viability, suggesting STOML2 as a potential therapeutic target for OA.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e9303825"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}