Frontiers in Genetics最新文献

{"title":"Genomic insights about the effect of sodium-glucose cotransporter 2 inhibitors: a systematic review.","authors":"Pavitraa Saravana Kumar, Yogapriya Chidambaram, G Shree Devi, Vettriselvi Venkatesan, Ramesh Sankaran, Nagendra Boopathy Senguttuvan, Thanikachalam Sadagopan, Dorairaj Prabhakaran","doi":"10.3389/fgene.2025.1571032","DOIUrl":"10.3389/fgene.2025.1571032","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure (HF) is a complex clinical syndrome with high morbidity and mortality, significantly burdening healthcare systems worldwide. Despite advances in therapy, effective treatment options remain limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for diabetes management, have demonstrated cardiovascular benefits, including reductions in HF hospitalizations and mortality. This systematic review examines the genomic effects of SGLT2 inhibitors in HF patients, focusing on gene expression, inflammatory biomarkers, and potential personalized treatment pathways.</p><p><strong>Methods: </strong>A systematic literature search of various databases was conducted up to November 2024, following PRISMA guidelines. Studies were included if they explored the genomic or molecular impacts of SGLT2 inhibitors in HF. Data extraction and analysis focused on gene expression changes, circulating biomarkers, and potential genomic mechanisms.</p><p><strong>Results: </strong>Of the 258 identified studies, three met the inclusion criteria. Key findings include: a) SGLT2 inhibitors downregulate pro-inflammatory genes in adipose tissue, reducing immune cell infiltration and ferroptosis; b) Genetic evidence highlights CXCL10 as a mediator of anti-inflammatory effects, with its inhibition linked to reduced HF risk; c) LRRTM2, a protein associated with synaptic formation, emerged as a critical mediator, with genetic links to reduced HF risk via SGLT2 inhibition.</p><p><strong>Discussion: </strong>This review underscores the genomic mechanisms through which SGLT2 inhibitors provide cardiovascular benefits. Key insights into gene expression modulation and protein interactions reveal pathways for personalized HF treatment. While findings are promising, further large-scale studies are needed to validate these mechanisms and their clinical implications.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD42024614674.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1571032"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hapten-labeled DNA probes can be stored and used in fluorescence <i>in situ</i> hybridization for decades.","authors":"Thomas Liehr, Niklas Padutsch, Stefanie Kankel","doi":"10.3389/fgene.2025.1569308","DOIUrl":"10.3389/fgene.2025.1569308","url":null,"abstract":"<p><p>In molecular cytogenetics, fluorescence <i>in situ</i> hybridization (FISH) is the main technique used. In both research and diagnostics, FISH depends on well-defined and mapped DNA probes that produce brilliant signals with minimal background, visible in metaphases and/or interphases. Such probes are either ready-to-use and commercially available or provided as unlabeled DNA. The latter can be obtained by flow sorting, microdissection, or by cloning DNA segments into appropriate bacterial vectors. Labeling can be done with either nonfluorescent or fluorescent haptens. According to international guidelines, such FISH probes must have a minimum shelf life, which is only between 2 and 3 years in human genetic diagnostics. The Molecular Cytogenetics Laboratory reporting here has been purchasing, producing, using, and storing FISH probes since the 1990s. For this study, the available stock of approximately 25,000 labeled probes was screened. A total of 581 FISH probes, labeled and approved 1-30 years before reuse, were selected for this study; of these, 75 were commercially available probes labeled 1-20 years ago. All of these probes, stored in the dark at -20°C, worked perfectly well in the FISH method. Although only slight to no differences in exposure times were observed over the years for self-labeled homemade probes, commercial probes labeled with SpectrumOrange had shorter exposure times and maintained them over the years. DNA probes labeled with SpectrumAqua/diethylaminocoumarin showed bright labeling for the first 3 years and then faded. Accordingly, it can be assumed that self-labeled homemade and commercial FISH probes can be stored stably in the dark and at -20°C for at least 30 years or longer. There is no need to test approved probes on a slide after the official expiry date. In practice, this suggests that a FISH probe tube that has been approved can be used in diagnostics until it is empty; there is no need to dispose of these expensive probes at any point due to their age.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1569308"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference-free deconvolution of complex samples based on cross-cell-type differential analysis: Systematic evaluations with various feature selection options.","authors":"Weiwei Zhang, Zhonghe Tian, Ling Peng","doi":"10.3389/fgene.2025.1570781","DOIUrl":"10.3389/fgene.2025.1570781","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic and epigenomic data from complex samples reflect the average level of multiple cell types. However, differences in cell compositions can introduce bias into many relevant analyses. Consequently, the accurate estimation of cell compositions has been regarded as an important initial step in the analysis of complex samples. A large number of computational methods have been developed for estimating cell compositions; however, their applications are limited due to the absence of reference or prior information. As a result, reference-free deconvolution has the potential to be widely applied due to its flexibility. A previous study emphasized the importance of feature selection for improving estimation accuracy in reference-free deconvolution.</p><p><strong>Methods: </strong>In this paper, we systematically evaluated five feature selection options and developed an optimal feature-selection-based reference-free deconvolution method. Our proposal iteratively searches for cell-type-specific (CTS) features by integrating cross-cell-type differential analysis between one cell type and the other cell types, as well as between two cell types and the other cell types, and performs composition estimation.</p><p><strong>Results and discussion: </strong>Comprehensive simulation studies and analyses of seven real datasets show the excellent performance of the proposed method. The proposed method, that is, reference-free deconvolution based on cross-cell-type differential (RFdecd), is implemented as an R package at https://github.com/wwzhang-study/RFdecd.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1570781"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very long-chain acyl-CoA dehydrogenase deficiency revisited: a retrospective genotype-phenotype analysis in a Saudi tertiary center.","authors":"Suzan Suliman Alhumaidi, Fahad Abdulrahman Algaeed, Meshari Fayez Aladhadh, Sara Abdulrahman Alkaff","doi":"10.3389/fgene.2025.1584817","DOIUrl":"10.3389/fgene.2025.1584817","url":null,"abstract":"<p><strong>Introduction: </strong>In this retrospective study, we analyzed clinical, biochemical, and genetic data and examined correlations between prevalent variants and outcomes of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency.</p><p><strong>Methods: </strong>Patients with VLCAD deficiency confirmed through molecular genetic testing at King Saud Medical City, Riyadh, Saudi Arabia, between 2016 and 2023 were included. Patients presented in the neonatal period with abnormal newborn screening and with metabolic decompensation and biochemical abnormalities clinically.</p><p><strong>Results: </strong>VLCAD deficiency was confirmed in 14 children. The mean age at presentation was 5.6 days. Clinically, 10 of the 14 patients presented with rhabdomyolysis. Hepatomegaly was observed in 9, cardiomyopathy in 7, and hypoglycemia in seven patients. In total, three variants were detected in the 14 patients: c.1310A>C (p.Glu437Ala) in 2; c.134C>A (p.Ser45X) in 6; and c.65C>A (p.Ser22Ter) in six patients. Currently, 12 patients are alive, whereas two have died. No significant relationship was identified between genotype and survival (<i>P</i> = 0.719). Variant C.1310A was associated with an excellent prognosis. Unlike those in other studies, variants c.65C>A and c.134C>A were associated with poor outcomes and early presentation with metabolic decompensation.</p><p><strong>Discussion: </strong>Long-term, prospective studies integrating metabolic profiling, functional assays, and multi-omics approaches will be essential to unravel the complex interplay between genetic variants and clinical expression and prognostic outcomes in VLCAD deficiency.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1584817"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of aging related genes in osteoarthritis.","authors":"Jian Du, Tian Zhou, Yanghui Dong, Yunchao Sun, Wei Peng","doi":"10.3389/fgene.2025.1561644","DOIUrl":"10.3389/fgene.2025.1561644","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a degenerative disease associated with aging. Although an increasing body of research suggests a close relationship between aging and OA, the underlying mechanisms remain unclear. This study explores the relationship between aging related genes (ARGs) and OA, providing potential new targets for understanding the pathogenesis and treatment of OA.</p><p><strong>Methods: </strong>The OA synovial tissue dataset was obtained from the GEO database, and differentially expressed genes (DEGs) were screened. The DEGs were intersected with ARGs to identify differentially expressed aging related genes (DEARGs), which were then subjected to functional enrichment analysis, PPI network analysis, and machine learning algorithms (LASSO and RF) to identify key genes. In addition, a nomogram was constructed based on the key genes to predict OA risk, and its diagnostic value was evaluated using ROC curves. Subsequently, the expression levels of the key genes were validated through qRT-PCR experiments. Finally, the CIBERSORT algorithm was applied to assess the proportion of immune cells and investigate the correlation between the key genes and immune cells.</p><p><strong>Results: </strong>A total of 34 DEARGs were identified. PPI network analysis revealed 12 key DEARGs. Subsequently, LASSO and RF algorithms identified ATF3, KLF4, NFKBIA, and SOD2 as key genes. Based on nomogram and ROC curve analysis, these four key genes demonstrated good diagnostic value. qRT-PCR showed that ATF3, KLF4, NFKBIA, and SOD2 were significantly downregulated in OA. Immune infiltration analysis revealed differences in Plasma cells, T cells follicular helper, Mast cells resting, T cells CD4 memory resting, NK cells activated, Monocytes, and Mast cells activated between the OA group and normal controls.</p><p><strong>Conclusion: </strong>ATF3, KLF4, NFKBIA and SOD2 are identified as novel biomarkers associated with aging in OA and may serve as potential therapeutic targets for OA treatment.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1561644"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and functional characteristics of a novel splice site variant in <i>L1CAM</i> caused X-linked hydrocephalus.","authors":"Shijie Zhou, Hao Zhang, Xue Li, Quan Chen, Zhihong Xu","doi":"10.3389/fgene.2025.1588709","DOIUrl":"10.3389/fgene.2025.1588709","url":null,"abstract":"<p><strong>Background: </strong>The <i>L1CAM</i> gene encodes an axonal glycoprotein belonging to the immunoglobulin supergene family that plays a crucial role in nervous system development. In this study, we reported a novel disease-causing mutation in the 3' splice site of <i>L1CAM</i> and provided some insight into fetal X-linked hydrocephalus.</p><p><strong>Methods: </strong>We obtained ultrasound images and collected samples from a couple and their fetuses. Fetal samples were acquired through amniocentesis, followed by extraction of genomic DNA. We conducted copy number variation sequencing (CNV-seq), karyotype analysis, and whole-exome sequencing The mutation site of the <i>L1CAM</i> gene was verified using PCR and Sanger sequencing, with splicing effects analyzed by bioinformatics analysis via BDGP, MaxEntScan and SpliceAI, as well as <i>in vitro</i> research via minigene assays.</p><p><strong>Results: </strong>The variant c.1380-1G > A in the first male fetus, located in the intron11 3' splice site of <i>L1CAM</i> (chrX:153868728), led to malfunction and hydrocephalus by aberrant mRNA splicing. The ultrasound examination of the fetus revealed the presence of hydrocephalus and partial agenesis of corpus callosum. In the subsequent pregnancy, the second male fetus exhibited no mutation in <i>L1CAM</i> as identified by Sanger sequencing, and the ultrasound results were within normal limits. No significant findings were observed in their CNV-seq and karyotype analysis. The second fetus was delivered uneventfully and no report of hydrocephalus through the telephone follow-up for 12 months.</p><p><strong>Conclusion: </strong>This study identified the variant c.1380-1G > A in <i>L1CAM</i> as new pathogenic mutation for the first time according to ACMG/AMP (American College of Medical Genetics and Genomics and the Association for Molecular Pathology)-based guidelines, which caused severe fetal X-linked hydrocephalus and partial agenesis of corpus callosum. This discovery expands the mutational landscape of <i>L1CAM</i>-associated disorders, highlights the diagnostic utility of integrating WES into prenatal workflows for unresolved fetal anomalies, and provides actionable insights for genetic counseling in families at risk of X-linked hydrocephalus.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1588709"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative transcriptomics and single-cell transcriptomics analyses reveal potential biomarkers and mechanisms of action in papillary thyroid carcinoma.","authors":"Wanchen Cao, Kai Gao, Yi Zhao","doi":"10.3389/fgene.2025.1536198","DOIUrl":"10.3389/fgene.2025.1536198","url":null,"abstract":"<p><strong>Objective: </strong>Papillary thyroid carcinoma (PTC) has a high recurrence rate and lacks reliable diagnostic biomarkers. This study aims to identify robust transcriptomic biomarkers for PTC diagnosis through integrative bioinformatics approaches and elucidate the cellular mechanisms underlying PTC pathogenesis at single-cell resolution.</p><p><strong>Methods: </strong>Based on the Gene Expression Omnibus (GEO) database, we downloaded PTC-related RNA-seq datasets (GSE3467, GSE3678, GSE33630, GSE65144, and GSE82208) and an scRNA-seq dataset (GSE191288). Among these, the RNA-seq dataset GSE3467 was used as the training dataset to perform differential gene expression analysis, GO and KEGG enrichment analyses, weighted gene co-expression network analysis (WGCNA), machine learning, ROC analysis, nomogram analysis, and GSEA for mining potential biomarkers. The remaining RNA-seq datasets (GSE3678, GSE33630, GSE65144, and GSE82208) were used as the validation datasets to validate these potential biomarkers. Based on the results from potential biomarker mining, the scRNA-seq dataset (GSE191288) was used to analyze and uncover key cell types and their mechanisms involved in the occurrence and development of PTC.</p><p><strong>Results: </strong>This study retrieved relevant PTC datasets from the GEO database and identified three biomarkers (ENTPD1, SERPINA1, and TACSTD2) through a series of bioinformatics analyses. GSEA suggested that these biomarkers may be involved in the occurrence and development of PTC by collectively regulating the cytokine-cytokine receptor interaction pathways. scRNA-seq analysis revealed tissue stem cells, epithelial cells, and smooth muscle cells as key cell types in PTC. Cell-cell communication analysis revealed that epithelial cells primarily interact with tissue stem cells and smooth muscle cells through two ligand-receptor pairs, namely, COL4A1-CD4 and COL4A2-CD4. The collagen signaling pathway was identified as the most dominant pathway, and violin plots demonstrated that ligands COL4A1 and COL4A2 were highly expressed in epithelial cells, while the receptor CD4 showed elevated expression in both tissue stem cells and smooth muscle cells. Pseudotime analysis demonstrated that these three cell types underwent three distinct differentiation stages, during which the expression levels of the biomarkers ENTPD1, SERPINA1, and TACSTD2 showed stage-specific trends.</p><p><strong>Conclusion: </strong>In summary, this study combines RNA-seq and scRNA-seq analysis techniques to identify ENTPD1, SERPINA1, and TACSTD2 as potential biomarkers for PTC at the transcriptomic level and tissue stem cells, epithelial cells, and smooth muscle cells as key cells in PTC at the cellular level. This study conducted in-depth research and analysis on these potential biomarkers and key cells, providing new research foundations and insights for future basic experimental research and the diagnosis and treatment of PTC in clinical settings.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1536198"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of colorectal cancer in genomic and transcriptomic at multi-level.","authors":"Qinglian Wen, Shuangyan Han, Yongxia Cui","doi":"10.3389/fgene.2025.1533817","DOIUrl":"10.3389/fgene.2025.1533817","url":null,"abstract":"<p><p>Colorectal cancer is a common malignant tumor in the gastrointestinal tract, and the mechanisms of its occurrence, development, and metastasis have always been the focus of the medical community's attention. The study of CRC genetic mechanisms began with the identification of oncogenes or tumor suppressor genes and their key pathways. With further research, researchers gradually realized that single genes or pathways alone could not explain the occurrence, development, and metastasis of CRC. The development of bulk sequencing technology has helped us to analyze the occurrence, development, and metastasis mechanisms of CRC from a multi-gene, multi-pathway, and multi-dimensional perspective, but it has not brought significant benefits to the clinical treatment of tumors. The main reason for this is that bulk sequencing technology relies on homogeneous cell grouping and cannot capture the heterogeneity between cells within the tumor and the interactions within the tumor microenvironment. The development of single-cell technology has made it possible to study the mechanisms of heterogeneity between cells within CRC and the interaction within the tumor microenvironment. This review discusses the mechanisms of CRC occurrence and development in three stages: traditional molecular biology level of single gene, bulk sequencing, and single-cell sequencing. These results show that the occurrence of CRC is the result of complex interactions between genetic and non-genetic factors in somatic cell evolution, where the heterogeneity between cells within the tumor and the tumor microenvironment are crucial for CRC progression.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1533817"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with dilated cardiomyopathy (DCM) by bioinformatics analysis and machine learning.","authors":"Yuhang Liu, Yong Wang, Wenyang Nie, Zhen Wang","doi":"10.3389/fgene.2025.1562891","DOIUrl":"10.3389/fgene.2025.1562891","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a globally prevalent and highly lethal condition, often accompanied by dilated cardiomyopathy (DCM), which increases the risk of cardiac complications. Early detection of DCM in CKD patients remains challenging, despite established research demonstrating the relationship between CKD and cardiac abnormalities.</p><p><strong>Methods: </strong>We retrieved expression matrices for DCM (GSE57338, GSE29819) and CKD (GSE104954) from GEO and a DCM scRNA-seq dataset (GSE145154). These were analyzed for differential gene expression and WGCNA. KEGG and GO analyses were performed on shared differentially expressed genes in DCM and CKD. Potential drugs for DCM were identified using CMAP. Machine learning methods LASSO, SVM-RFE, and RF were used to find biomarkers and develop a diagnostic nomogram for CKD-associated DCM, validated with external datasets. Single-gene GSEA was conducted to understand model gene mechanisms in CKD-associated DCM. Immune cell infiltration was analyzed with CIBERSORT, and single-cell sequencing examined model gene distribution and expression in the heart.</p><p><strong>Results: </strong>Our examination of the expression matrix datasets associated with DCM and CKD revealed 115 key model genes that are shared by the two disorders as well as 47 genes that are differently expressed. These 47 differentially expressed genes were primarily linked to immune regulation and inflammation, according to enrichment analysis. CMAP analysis suggested withaferin-a, droxinostat, fluorometholone, and others as potential DCM treatments. Machine learning identified MNS1 and HERC6 as significant CKD-associated DCM biomarkers. A diagnostic nomogram using these genes was developed, showing strong discriminative power and clinical utility. MNS1 and HERC6 are implicated in metabolism, inflammation, immunity, and heart function. Immune cell infiltration analysis indicated dysregulation in DCM, with MNS1 and HERC6 correlating with immune cells. Single-cell sequencing showed MNS1 and HERC6 expression in endothelial cells and fibroblasts, respectively.</p><p><strong>Conclusion: </strong>We identified MNS1 and HERC6 as biomarkers and developed a new diagnostic nomogram based on them for the timely diagnosis of CKD patients presenting with DCM complications. This study's findings offer novel insights into potential diagnostic methods and therapeutic strategies regarding the coexistence of CKD and DCM.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1562891"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4⁺ T cells through the miR-424-5p/SGK1 axis in psoriasis.","authors":"Ziqi Yuan, Xue Zeng, Xiwei Zhang, Chenglai Xia, Xuebiao Peng","doi":"10.3389/fgene.2025.1521470","DOIUrl":"10.3389/fgene.2025.1521470","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4⁺ T cell differentiation remains unclear.</p><p><strong>Methods: </strong>Exosomes were extracted from HaCaT cells using a reagent kit and verified by TEM (Transmission Electron Microscope), NTA (Nanoparticle Tracking Analysis), and Western Blot. We incubated exosomes with CD4⁺ T cells and detected the distribution of AGAP2-AS1 by fluorescence microscopy. Flow cytometry and ELISA were used to detect CD4⁺ T cell differentiation. In addition, the relationship between AGAP2-AS1/miR-424-5p/SGK1 and its effect on CD4⁺ T cell differentiation were confirmed by bioinformatics analysis, dual luciferase reporter gene experiments, quantitative real-time PCR, flow cytometry, and ELISA.</p><p><strong>Results: </strong>We found that exosomes derived from TNF-α-treated HaCaTs were able to deliver AGAP2-AS1 to CD4⁺ T cells, promoting Th1 and Th17 differentiation. In CD4⁺ T cells, AGAP2-AS1 promotes Th1 and Th17 differentiation via the miR-424-5p/SGK1 axis.</p><p><strong>Conclusion: </strong>Psoriatic HaCaTs deliver AGAP2-AS1 to CD4⁺ T cells via exosomes, inducing Th1 and Th17 differentiation through the miR-424-5p/SGK1 axis, thereby promoting the progression of psoriasis. These findings provide novel insights into the pathogenesis of psoriasis and potential therapeutic targets.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1521470"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}