Journal of Gene Medicine最新文献

{"title":"The Role of MiRNAs in Moyamoya Disease: Vascular Remodeling and Stroke Risk","authors":"Heba Ibrahim Abd El-Moaty,&nbsp;Ahmed S. Doghish,&nbsp;Reda M. Mansour,&nbsp;Mina Y. George,&nbsp;Nehal I. Rizk,&nbsp;Rabab S. Hamad,&nbsp;Sherif S. Abdel Mageed,&nbsp;Osama A. Mohammed,&nbsp;Mustafa Ahmed Abdel-Reheim,&nbsp;Hesham A. El-Mahdy,&nbsp;Mohamed A. Elkady,&nbsp;Ahmed Ismail,&nbsp;Eman S. Sawan,&nbsp;Hanan Elimam,&nbsp;Mahmoud A. Elrebehy,&nbsp;Mohamed Hemdan","doi":"10.1002/jgm.70029","DOIUrl":"https://doi.org/10.1002/jgm.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Moyamoya disease (MMD) is a rare degenerative stenosis and occlusive cerebrovascular illness. It is characterized by cerebral ischemia and/or cerebral hemorrhage as the two main clinical signs. It is a common cause of stroke in both children and adults. Several recent studies illustrated the crucial role of microRNAs (miRNAs) in the pathophysiology of MMD via the regulation of endothelial cells and smooth muscle cells. Furthermore, other studies highlighted the decisive role of miRNAs in the underlying molecular pathophysiological mechanisms in MMD via regulation of cellular proliferation, angiogenesis, extracellular matrix remodeling, and vascular inflammation. This review aims to explore the involvement of miRNAs in MMD pathogenesis and to assess their potential use as biomarkers for stroke risk and their utility as therapeutic targets for the treatment of MMD.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-Inducible Factor HIF1α Regulates the Expression of SLC7A1 to Mediate Erastin-Induced Ferroptosis in Cervical Cancer Cells","authors":"Yanqing Huang,&nbsp;Yan Lei,&nbsp;Yanling Li","doi":"10.1002/jgm.70027","DOIUrl":"https://doi.org/10.1002/jgm.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the regulation of hypoxia-inducible factor 1α (HIF1α) on cationic amino acid transporter 1 (SLC7A1) expression and its potential mechanism YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in Erastin-induced ferroptosis in human cervical cancer (CaCx) cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human CaCx cell lines (HeLa and SiHa) were cultured in vitro under normoxic or hypoxic conditions and treated with Erastin (30 μM, a stimulator of ferroptosis) before cell transfection with small interfering RNAs against HIF1α, YTHDF1, or SLC7A1 (si-HIF1α, si-YTHDF1 or si-SLC7A1). Cell viability and the levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), and Fe²⁺ were measured, followed by transmission electron microscopy for ferroptosis-associated mitochondrial morphological changes in CaCx cells. The interaction of HIF1α in YTHDF1 was determined by JASPAR database and dual-luciferase reporter assay. Chromatin immunoprecipitation (ChIP) was performed to determine the enrichment of HIF1α at YTHDF1 promoter. The N6-methyladenosine (m6A) methylation level of SLC7A1 was detected using Methylated RNA Immunoprecipitation (MeRIP) assay. In vivo experiments were conducted on nude mice via injection of HeLa or SiHa cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Erastin repressed cell growth and induced ferroptosis in CaCx cells, while hypoxia pretreatment partly reversed the Erastin-induced cytotoxicity and ferroptosis in CaCx cells. Erastin caused low HIF1α levels in CaCx cells, while hypoxia pretreatment partially counteracted this downregulation. Knockdown of HIF1α and YTHDF1 downregulated SLC7A1 expression and promoted Erastin-induced ferroptosis in hypoxic CaCx cells. Additionally, HIF1α regulated YTHDF1 expression, leading to increased m6A methylation and activation of SLC7A1. The in vivo xenograft model further validated that Erastin inhibited tumor growth in CaCx, while the antitumor effect of Erastin was partially reversed by HIF1α overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HIF1α regulates the expression of YTHDF1, thereby enhancing the m6A modification level of SLC7A1, promoting its expression, and ultimately inhibiting Erastin-induced ferroptosis in CaCx cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Artificial Neural Network-Based Gene Screening and Immune Cell Infiltration Analysis of Osteosarcoma Feature”","authors":"","doi":"10.1002/jgm.70028","DOIUrl":"https://doi.org/10.1002/jgm.70028","url":null,"abstract":"<p>\u0000 <span>Shi, S</span>, <span>Guo, Y</span>, <span>Wang, Q</span>, <span>Huang, Y</span>. <span>Artificial Neural Network-Based Gene Screening and Immune Cell Infiltration Analysis of Osteosarcoma Feature</span>. <i>J Gene Med.</i> <span>2024</span>; <span>26</span>(<span>1</span>):e3622, https://doi.org/10.1002/jgm.3622.\u0000 </p><p>The article lacks an ethical statement. Please add it in the statement section.</p><p>This study was approved by the Clinical Research Ethics Committee of Honghui Hospital Affiliated to Xi'an Jiaotong University (Approval No. 20210907). The ethics committee has comprehensively reviewed the research project titled “Screening of Osteosarcoma Characteristic Genes Based on Artificial Neural Networks and Analysis of Immune Cell Infiltration” and confirmed that it complies with ethical principles. This study was conducted in strict accordance with the principles of the Declaration of Helsinki.</p><p>We apologize for this error.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FPPS Downregulation Attenuates Endoplasmic Reticulum Stress in Pulmonary Epithelial Cells","authors":"Defeng Ye,&nbsp;Chengcheng Zhang,&nbsp;Wencheng Shao,&nbsp;Lin Lin,&nbsp;Xi Chen,&nbsp;Liang Wu","doi":"10.1002/jgm.70024","DOIUrl":"https://doi.org/10.1002/jgm.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>The airway epithelium is the primary target of the trachea in lung transplant rejection and epithelial cell injury are frequently observed in lung transplants. Farnesyl pyrophosphate synthase (FPPS), a pivotal enzyme in the mevalonate pathway, synthesizes isoprenoid compounds like FPP and GGPP. This study found upregulated expression of FPPS in the epithelial cells of the tracheal transplant rat model and the use of the FPPS inhibitor zoledronic acid reduced the tracheal epithelial cell damage. Using CRISPR/CAS9, FPPS was knocked down in pulmonary-derived epithelial cells, and RNA sequencing analysis revealed alterations in the gene expression profile, notably involving significant reductions in multiple endoplasmic reticulum stress-related genes, including the ATF4/TRIB3 pathway and the ERN1/XBP1 pathway, which were further confirmed at the protein level. Additionally, treatment with zoledronic acid exhibited inhibitory effects on endoplasmic reticulum stress in the tracheal transplant rat model. Furthermore, FPPS knockdown and Inhibition were found to suppress the expression of multiple amino acid transporters, including SLC7A5, resulting in decreased intracellular levels of multiple amino acids, reduced mTORC1 pathway activity, and enhanced autophagic function. In summary, this study identified the protective roles of FPPS inhibition in epithelial cells of the tracheal transplant model, potentially mediated through reductions in endoplasmic reticulum stress, decreased mTORC1 activity, and augmented downstream autophagic processes.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products and lncRNAs in Renal Cell Carcinoma: Emerging Therapeutic Approaches","authors":"Ahmed S. Doghish,&nbsp;Mai A. Abd-Elmawla,&nbsp;Nora M. Aborehab,&nbsp;Abdullah F. Radwan,&nbsp;Heba R. Ghaiad,&nbsp;Khloud Nassar,&nbsp;Osama A. Mohammed,&nbsp;Hanan Elimam","doi":"10.1002/jgm.70026","DOIUrl":"https://doi.org/10.1002/jgm.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Renal cell carcinoma (RCC) is a malignant neoplasm arising from the renal epithelium and constitutes approximately 2% of global cancer diagnoses and mortalities. With increasing prevalence, RCC remains a pressing clinical challenge, particularly because of its resistance to conventional therapies and poor outcomes in advanced stages. Long noncoding RNAs (lncRNAs) have been proposed as key molecular mediators in RCC, orchestrating critical pathways such as epithelial-to-mesenchymal transition (EMT), cellular proliferation, apoptosis, angiogenesis, and metastasis. Their roles in therapeutic resistance, including chemoresistance and radioresistance, further highlight their impact on treatment outcomes. Additionally, the potential of natural compounds such as curcumin, quercetin, and resveratrol to target lncRNA-mediated pathways has garnered attention, offering insights into novel therapeutic strategies. This review examines the biogenic pathways and multifaceted functions of lncRNAs, shedding light on their influence on RCC pathophysiology and posttranscriptional regulation. In addition, this review emphasizes the repercussions of natural compounds as lncRNA-targeted therapies, thus offering a comprehensive perspective on emerging strategies that may lead to more effective and personalized treatments.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Study of Diabetes Mellitus (Type 2)–Associated Genes in Homo sapiens (Human)","authors":"Rizwan Shaukat,&nbsp;Amjad Hussain,&nbsp;Muhammad Sajid Hamid Akash,&nbsp;Kanwal Rehman,&nbsp;Muhammad Imran,&nbsp;Enas Ali,&nbsp;Meher Ali,&nbsp;Khayala Mammadova,&nbsp;Afnan Jan,&nbsp;Ajmal Khan,&nbsp;Shoaib Khan,&nbsp;Muhammad Adnan Ayub,&nbsp;Munzer Ullah,&nbsp;Ammara Sohail,&nbsp;Hafsa Arshad","doi":"10.1002/jgm.70025","DOIUrl":"https://doi.org/10.1002/jgm.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and impaired secretion, necessitating the identification of new markers to target its development and complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study conducted a genome-wide study on diabetes mellitus (type 2)-associated genes in <i>Homo sapiens</i> to better understand their role and explore their potential mechanisms. Twenty genes linked to type 2 diabetes were found in this study, and the various analyses, including chromosome localization, synteny analysis, physiochemical features, phylogenetic analysis, motif analysis, protein–protein interactions, gene structure, and expression profiles, were examined using a variety of bioinformatics tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings revealed that the <i>FOS</i> gene was highly acidic with an isoelectric point (<i>pI =</i> 4.77); however, the <i>VEGFA</i> gene was greatly basic with an isoelectric point (<i>pI</i> = 9.24) as compared to the chosen genes in <i>H. sapiens</i>. A chromosomal localization analysis showed that diabetes-associated genes were randomly positioned on human chromosomes, with four genes (<i>ELMO1</i>, <i>GCK</i>, <i>GNAI</i>, and <i>CYP3A4</i>) on Chr7, while seven individual genes included <i>PPM1K</i>, <i>TDO2</i>, <i>GALNT7</i>, <i>PIK3R1</i>, <i>VEGFA</i>, <i>PTGS1</i>, <i>TCF7L2</i>, <i>GNG3</i>, <i>SIRT4</i>, and <i>SSTR2</i> on chromosome numbers 5, 6, 9, 10, 11, 12, and 17, respectively. There were no tandem duplication events detected. Thirteen taxa (consisting of 26 genes) were identified by a phylogenetic tree, and seven taxa revealed orthologous conservation. Motif analysis showed the top 5 motifs were expected with identical frequency except motif 1 and motif 2. Strong interactions were seen between the <i>ELMO1</i> gene and all predictive partners bearing a higher bitscore value of 1439.5 than other genes indicated by protein–protein interaction. Regarding gene structure analysis, the <i>CHL1</i> gene showed a maximum number of 26 exons as compared with other genes in its structure. The highest expression level was exhibited by the <i>CYP3A4</i> gene in the liver and pancreas as compared with other genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present study provides insight into diabetes mellitus (type 2)–associated genes and can serve as a basis for their functional analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Analysis of Novel circRNA-miRNA-mRNA Axis in BRAFV600E Melanoma: Implications for Primary to Metastasis Transformation and TIME Modulation","authors":"Hemangini Naik,&nbsp;Rajat Choudhary,&nbsp;V. Badireenath Konkimalla","doi":"10.1002/jgm.70023","DOIUrl":"https://doi.org/10.1002/jgm.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The BRAF^V600E mutation drives metastatic transition by altering the tumor immune microenvironment (TIME) through transcriptional and post-transcriptional regulation. Recent studies identify circular RNA (circRNA) and micro-RNA (miRNA) as key regulators in melanoma. This study uses <i>in silico</i> analysis to explore the circRNA-miRNA-mRNA axis in melanoma progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed primary (<i>n</i> = 42) and metastatic (<i>n</i> = 89) tumor samples from TCGA (SKCM), including their BRAF status, to identify markers in both tumor types and explored their association with immune cells within TIME. The key regulatory markers were verified using ROC curve analysis, IHC data from HPA database, and from an external dataset. Further, the circRNA-miRNA-mRNA axis was established using Cytoscape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our comprehensive analysis identifies SYK, HMOX1, IL33, CFH, FGF1, COL8A1, and ADAMTS3 as the primary gene signatures, while VCAM-1 and SNAI2 dominate as prominent metastatic markers associated with BRAF^V600E and immune subtype. Among the immune infiltrating group, macrophages M1 and M2, CD8⁺ T-cells, and T_regs show a positive correlation with significant infiltration within TIME. We screened miRNA targets and circular sponges, built a circRNA-miRNA-mRNA network involving two circRNAs (hsa-circ-0011617 and hsa-circ-0011623) and three miRNAs (hsa-miR-1246, hsa-miR-346, and hsa-miR-1197) connected to the identified signature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our study reveals two circRNAs that might have a potential role in primary to metastasis transition in the BRAF-mutated melanoma within TIME via the circRNA–miRNA–mRNA axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sp2 Transcription Factor Alleviates Chondrocyte Loss in Osteoarthritis by Repressing the DVL1-Dependent Wnt/β-Catenin Signaling Pathway","authors":"Yuan Lin,&nbsp;Xinpeng Zheng,&nbsp;Xiaolei Chen,&nbsp;Yue Wang","doi":"10.1002/jgm.70021","DOIUrl":"https://doi.org/10.1002/jgm.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Osteoarthritis (OA) ranks as the most prevalent condition affecting the musculoskeletal system, where chondrocyte loss or dysfunction plays a crucial pathogenic role. This study is aimed at investigating key molecular cascades implicated in chondrocyte loss and cartilage injury in OA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A mouse model of OA was generated by destabilization of the medial meniscus. Histological staining was performed to evaluate the pathological changes in the knee joint tissue, the cartilage morphology, and the osteoblast population. A high-throughput sequencing analysis was performed to analyze aberrantly expressed genes in OA cartilage. Gain- or loss-of-function assays of dishevelled segment polarity protein 1 (DVL1) and Sp2 transcription factor (SP2) were carried out to analyze their effects on cartilage injury in mice and chondrocyte apoptosis in vitro. The interaction between SP2 and DVL1 was verified by chromatin immunoprecipitation and luciferase assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DVL1 was expressed at aberrantly high levels in the cartilage of OA mice. Its knockdown suppressed protein levels and transcriptional activity of β-catenin, thereby reducing cartilage damage and loss in mice. In vitro, chondrocyte apoptosis was inhibited upon DVL1 silencing. SP2, poorly expressed in OA cartilage, was found to repress DVL1 transcription by binding to its promoter. Overexpression of SP2 similarly alleviated cartilage injury and chondrocyte loss; however, these effects were negated by the additional DVL1 overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that SP2 represses DVL1 transcription and inactivates the Wnt/β-catenin signaling, thus alleviating chondrocyte loss and cartilage injury in OA mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Links Between Micronutrients and Cardiac Traits: Roles of Vitamins A1, B9, and D","authors":"Lingwei Liu,&nbsp;Yongxi Cheng,&nbsp;Shujun Yan,&nbsp;Jian Zhou","doi":"10.1002/jgm.70022","DOIUrl":"https://doi.org/10.1002/jgm.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Micronutrients, such as vitamins and minerals, are essential for cardiac health, but their effects on cardiac structure and function remain unclear. This study aimed to investigate the causal impact of micronutrients on cardiac traits through Mendelian randomization (MR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample MR approach was employed to assess the causal effects between 14 micronutrients and 98 cardiac traits from various consortia and cohorts. Inverse variance-weighted (IVW) MR analyses were conducted, alongside a range of sensitivity analyses to confirm robustness. Both exposure and outcome populations were of European descent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant associations were found for Vitamins A1, B9, and D with various cardiac traits. Vitamin D was linked to reduced left ventricular end-diastolic myocardial wall thickness (IVW <i>β</i>: −0.16; 95% CI: −0.29 to −0.03; <i>p</i> = 0.01) and increased regional longitudinal and radial strains of the left ventricle (IVW <i>β</i>: 0.19; <i>p</i> = 0.03; IVW <i>β</i>: 0.17; <i>p</i> = 0.04). Vitamin A1 was associated with reduced left ventricular mass (IVW <i>β</i>: −10.23; <i>p</i> = 0.03; IVW <i>β</i>: −13.72; <i>p</i> = 0.007), both with and without body surface area and blood pressure adjustments. Vitamin B9 was associated with reductions in left ventricular mass (IVW <i>β</i>: −0.09; <i>p</i> = 0.04), myocardial wall thickness (IVW <i>β</i>: −0.13; <i>p</i> = 0.04), and ascending aorta maximum area (IVW <i>β</i>: −0.19; <i>p</i> = 0.01). No significant heterogeneity or horizontal pleiotropy was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vitamins A1, B9, and D exhibit beneficial effects on cardiac structure and function, offering potential targets for nutritional intervention in at-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying GAP43, NMU, and TEX29 as Potential Prognostic Biomarkers for COPD Combined With Lung Cancer Patients Using Machine Learning","authors":"Zhilong Xu,&nbsp;Kaiyao Zhang,&nbsp;Ao Zeng,&nbsp;Yanze Yin,&nbsp;KeYi Chen,&nbsp;Chao Wang,&nbsp;Xinyun Fang,&nbsp;Abudumijiti Abuduwayiti,&nbsp;JiaRui Wang,&nbsp;Jie Dai,&nbsp;Gening Jiang","doi":"10.1002/jgm.70020","DOIUrl":"https://doi.org/10.1002/jgm.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) and lung cancer, frequently comorbid conditions intricately linked through smoking, represent significant global health challenges. COPD is a common comorbidity in nonsmall cell lung cancer (NSCLC) patients and has been shown to negatively impact prognosis. However, the molecular mechanisms underlying the interplay between COPD and lung cancer remain unclear. This study aims to identify differentially expressed genes (DEGs) associated with COPD-related lung cancer and, using various machine learning (ML) algorithms, uncover potential biomarkers for prognosis. We analyzed RNA sequencing data from 41 lung cancer patients (with and without COPD) and identified 61 DEGs, all of which were upregulated in solitary lung cancer compared to COPD-associated cases. Functional enrichment analysis revealed that these genes are involved in biological processes such as granulocyte chemotaxis and smooth muscle contraction and molecular functions including neuropeptide receptor binding. Three ML methods—support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO), and random forest—were applied to prioritize key biomarkers. Three genes, <i>GAP43</i>, <i>NMU</i>, and <i>TEX29</i>, were consistently selected across all methods. Further analysis demonstrated significant correlations between these genes and immune cell infiltration, with notable differences in immune cell composition observed in COPD-associated lung cancer. High expression levels of <i>GAP43</i>, <i>NMU</i>, and <i>TEX29</i> were associated with poor survival outcomes in lung cancer patients, as validated through survival analysis of TCGA database data. Our findings suggest that these genes may serve as diagnostic and prognostic biomarkers for COPD-related lung cancer, thereby providing insights into potential therapeutic targets. Further studies with larger cohorts are required to validate these results and elucidate the underlying molecular mechanisms.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}