首页 > 最新文献

Comparative and Functional Genomics最新文献

英文 中文
Identification and Validation of the Key Genes of Diabetic Vasculopathy: Evidence Based on Bioinformatics Analysis and Animal Study 糖尿病血管病变关键基因的鉴定与验证:基于生物信息学分析和动物实验的证据
Pub Date : 2025-10-24 DOI: 10.1155/ijog/7850852
Feng Li, Chi Geng, Xing Xu, Yu-Lun Zhou, Xin-Ru Guo, Rui-Tao Wang, You Zhang, Si-Liang Peng, Meng-Chao Jin, Jian Huang, Hui-Yu Bai, Hui Li, Xiao-Song Gu

Backgrounds

The mechanisms contributing to diabetic vasculopathy have not been fully understand.

Methods

First, we identified differentially expressed genes (DEGs) of diabetic vasculopathy via GSE13760. Enrichment analysis was conducted. We utilized the cMAP database to identify potential small-molecular drugs targeting diabetic vasculopathy based on upregulated DEGs. Hub genes were extracted from protein–protein interaction (PPI) networks, and their expression and correlation patterns were further evaluated. Key genes implicated in diabetic vasculopathy were determined by integrating three distinct algorithmic approaches. Additionally, we constructed mRNA–miRNA and mRNA–transcription factor (TF) regulatory networks and performed immune infiltration as well as single-cell RNA sequencing (scRNA-seq) analyses. Finally, animal studies were carried out to provide preliminary experimental validation.

Results

One hundred thirty-nine DEGs were identified in the comparison between Type 2 diabetes mellitus (T2DM) and control (Con) arterial samples. Then, enrichment analysis revealed that the DEGs were associated with several key pathways, including cytokine–cytokine receptor interaction, regulation of phosphatidylinositol 3-kinase activity, and the TGF-beta signaling pathway. Ten leading small-molecular compounds with therapeutic potential for diabetic vasculopathy were identified. Among the upregulated genes, BMP4 and LEP were selected as key candidates. Regulatory network analyses, including mRNA–miRNA and mRNA–TF interactions, along with immune infiltration profiling, suggested that multiple miRNAs, TFs, and immune cells may collectively influence BMP4 and LEP expression. scRNA-seq further indicated predominant expression of BMP4 within endothelial cells and fibroblasts. Finally, experimental validation in the T2DM mouse model corroborated the expression patterns of these key genes and enrichment findings.

Conclusions

Findings indicate that the two upregulated genes, BMP4 and LEP, are implicated in the pathophysiology of diabetic vasculopathy.

背景糖尿病血管病变的发生机制尚不完全清楚。方法首先,通过GSE13760检测糖尿病血管病变的差异表达基因(DEGs)。进行富集分析。我们利用cMAP数据库,根据上调的deg来确定潜在的针对糖尿病血管病变的小分子药物。从蛋白-蛋白相互作用(PPI)网络中提取枢纽基因,并进一步评估其表达和相关模式。通过整合三种不同的算法方法来确定糖尿病血管病变的关键基因。此外,我们构建了mRNA-miRNA和mrna -转录因子(TF)调控网络,并进行了免疫浸润和单细胞RNA测序(scRNA-seq)分析。最后,进行动物实验以提供初步的实验验证。结果2型糖尿病(T2DM)与对照(Con)动脉样本共鉴定出139个deg。然后,富集分析显示,deg与几个关键途径相关,包括细胞因子-细胞因子受体相互作用、磷脂酰肌醇3-激酶活性调节和tgf - β信号通路。确定了10种具有治疗糖尿病血管病变潜力的主要小分子化合物。在上调基因中,BMP4和LEP被选为关键候选基因。调控网络分析,包括mRNA-miRNA和mRNA-TF相互作用,以及免疫浸润谱,表明多种mirna、tf和免疫细胞可能共同影响BMP4和LEP的表达。scRNA-seq进一步显示内皮细胞和成纤维细胞中主要表达BMP4。最后,在T2DM小鼠模型中的实验验证证实了这些关键基因的表达模式和富集结果。结论BMP4和LEP这两个基因的上调与糖尿病血管病变的病理生理有关。
{"title":"Identification and Validation of the Key Genes of Diabetic Vasculopathy: Evidence Based on Bioinformatics Analysis and Animal Study","authors":"Feng Li,&nbsp;Chi Geng,&nbsp;Xing Xu,&nbsp;Yu-Lun Zhou,&nbsp;Xin-Ru Guo,&nbsp;Rui-Tao Wang,&nbsp;You Zhang,&nbsp;Si-Liang Peng,&nbsp;Meng-Chao Jin,&nbsp;Jian Huang,&nbsp;Hui-Yu Bai,&nbsp;Hui Li,&nbsp;Xiao-Song Gu","doi":"10.1155/ijog/7850852","DOIUrl":"https://doi.org/10.1155/ijog/7850852","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>The mechanisms contributing to diabetic vasculopathy have not been fully understand.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, we identified differentially expressed genes (DEGs) of diabetic vasculopathy via GSE13760. Enrichment analysis was conducted. We utilized the cMAP database to identify potential small-molecular drugs targeting diabetic vasculopathy based on upregulated DEGs. Hub genes were extracted from protein–protein interaction (PPI) networks, and their expression and correlation patterns were further evaluated. Key genes implicated in diabetic vasculopathy were determined by integrating three distinct algorithmic approaches. Additionally, we constructed mRNA–miRNA and mRNA–transcription factor (TF) regulatory networks and performed immune infiltration as well as single-cell RNA sequencing (scRNA-seq) analyses. Finally, animal studies were carried out to provide preliminary experimental validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred thirty-nine DEGs were identified in the comparison between Type 2 diabetes mellitus (T2DM) and control (Con) arterial samples. Then, enrichment analysis revealed that the DEGs were associated with several key pathways, including cytokine–cytokine receptor interaction, regulation of phosphatidylinositol 3-kinase activity, and the TGF-beta signaling pathway. Ten leading small-molecular compounds with therapeutic potential for diabetic vasculopathy were identified. Among the upregulated genes, BMP4 and LEP were selected as key candidates. Regulatory network analyses, including mRNA–miRNA and mRNA–TF interactions, along with immune infiltration profiling, suggested that multiple miRNAs, TFs, and immune cells may collectively influence BMP4 and LEP expression. scRNA-seq further indicated predominant expression of BMP4 within endothelial cells and fibroblasts. Finally, experimental validation in the T2DM mouse model corroborated the expression patterns of these key genes and enrichment findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Findings indicate that the two upregulated genes, BMP4 and LEP, are implicated in the pathophysiology of diabetic vasculopathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/7850852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366866","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}
引用次数: 0
Mapping the Research Landscape of Exercise and Breast Cancer: A Bibliometric Analysis From 2020 to 2024 绘制运动与乳腺癌的研究图景:从2020年到2024年的文献计量学分析
Pub Date : 2025-10-23 DOI: 10.1155/ijog/2972077
Jian Li, LiYing Qiang, MingYue Jiao, BinBin Zhang

Even though there is strong evidence that exercise improves breast cancer patients′ quality of life, treatment tolerance, and survival, disparate research initiatives and uneven clinical acceptance underscore the need for a thorough synthesis of trends, partnerships, and gaps. This bibliometric analysis systematically maps the research landscape of exercise and cardiovascular disease (CVD) from 2020 to 2024, aiming to identify trends, influential works, and knowledge gaps in this critical field. Utilizing data from the Web of Science (WoS) and VOSviewer, the study analyzed 314 articles through cocitation, coword, and co-occurrence analyses. Key findings reveal exponential growth in citations, driven by seminal guidelines (e.g., ESC 2021 and WHO 2020) and studies on sedentary behavior and pandemic-related activity changes. The intellectual structure is anchored by three themes: evidence-based guidelines, risk quantification (e.g., dose–response relationships), and behavioral interventions. Dominant journals include the British Journal of Sports Medicine and JAMA, while influential authors like Dominique Hansen and Emmanuel Stamatakis shape the field. Geographic disparities highlight Western-centric research dominance, though emerging contributions from Asia and Europe are noted. The study identifies gaps in mechanistic research, personalized exercise prescriptions, and equitable translation of evidence into practice. Practical implications call for standardized clinical protocols, dual public health messaging (activity promotion and sedentary reduction), and digital health integration. This analysis provides a roadmap for future research, emphasizing transdisciplinary collaboration to optimize CVD prevention through physical activity.

尽管有强有力的证据表明,运动可以改善乳腺癌患者的生活质量、治疗耐受性和生存率,但不同的研究计划和不平衡的临床接受程度强调了对趋势、合作伙伴和差距进行全面综合的必要性。这项文献计量分析系统地绘制了2020年至2024年运动和心血管疾病(CVD)的研究图景,旨在确定这一关键领域的趋势、有影响力的作品和知识差距。该研究利用来自Web of Science (WoS)和VOSviewer的数据,通过引用、coword和共现分析分析了314篇文章。主要发现显示,在开创性指南(例如《ESC 2021》和《世卫组织2020》)以及关于久坐行为和大流行相关活动变化的研究的推动下,被引用的次数呈指数级增长。知识结构以三个主题为基础:循证指南、风险量化(例如,剂量-反应关系)和行为干预。占主导地位的期刊包括《英国运动医学杂志》(British Journal of Sports Medicine)和《美国医学会杂志》(JAMA),而多米尼克·汉森(Dominique Hansen)和伊曼纽尔·斯塔马塔基斯(Emmanuel Stamatakis)等有影响力的作者则塑造了这个领域。地理差异凸显了以西方为中心的研究优势,尽管亚洲和欧洲的新兴贡献也得到了注意。该研究指出了机械研究、个性化运动处方以及将证据公平地转化为实践方面的差距。实际影响需要标准化临床方案、双重公共卫生信息传递(促进活动和减少久坐)以及数字健康整合。这一分析为未来的研究提供了路线图,强调跨学科合作,通过体育活动优化心血管疾病的预防。
{"title":"Mapping the Research Landscape of Exercise and Breast Cancer: A Bibliometric Analysis From 2020 to 2024","authors":"Jian Li,&nbsp;LiYing Qiang,&nbsp;MingYue Jiao,&nbsp;BinBin Zhang","doi":"10.1155/ijog/2972077","DOIUrl":"https://doi.org/10.1155/ijog/2972077","url":null,"abstract":"<p>Even though there is strong evidence that exercise improves breast cancer patients′ quality of life, treatment tolerance, and survival, disparate research initiatives and uneven clinical acceptance underscore the need for a thorough synthesis of trends, partnerships, and gaps. This bibliometric analysis systematically maps the research landscape of exercise and cardiovascular disease (CVD) from 2020 to 2024, aiming to identify trends, influential works, and knowledge gaps in this critical field. Utilizing data from the Web of Science (WoS) and VOSviewer, the study analyzed 314 articles through cocitation, coword, and co-occurrence analyses. Key findings reveal exponential growth in citations, driven by seminal guidelines (e.g., ESC 2021 and WHO 2020) and studies on sedentary behavior and pandemic-related activity changes. The intellectual structure is anchored by three themes: evidence-based guidelines, risk quantification (e.g., dose–response relationships), and behavioral interventions. Dominant journals include the <i>British Journal of Sports Medicine</i> and <i>JAMA</i>, while influential authors like Dominique Hansen and Emmanuel Stamatakis shape the field. Geographic disparities highlight Western-centric research dominance, though emerging contributions from Asia and Europe are noted. The study identifies gaps in mechanistic research, personalized exercise prescriptions, and equitable translation of evidence into practice. Practical implications call for standardized clinical protocols, dual public health messaging (activity promotion and sedentary reduction), and digital health integration. This analysis provides a roadmap for future research, emphasizing transdisciplinary collaboration to optimize CVD prevention through physical activity.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/2972077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366540","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}
引用次数: 0
Identification of Key Periodontitis Genes and Their Mechanisms of Action Using Comprehensive Multiple Microarray Analysis and Mendelian Randomization Methods 利用综合多芯片分析和孟德尔随机化方法鉴定牙周炎关键基因及其作用机制
Pub Date : 2025-10-23 DOI: 10.1155/ijog/5587468
Kezhen Xiang, Conghua Li, Na Hu

Background

Periodontitis, a chronic inflammatory disease, damages the soft tissues and bones around the teeth. Affecting adults, mild periodontitis is common, while severe cases impact up to 20% of individuals, with a prevalence of 45%–50%. This study was aimed at identifying and analyzing the functions of genes differentially expressed in periodontitis through bioinformatics. Additionally, we aimed to validate the causal relationships of these genes with periodontitis using Mendelian randomization.

Methods

The investigation included 557 samples obtained from 210 patients suffering from periodontitis within the GEO database, focusing on the differential expression of genes and conducting a weighted gene coexpression network analysis (WGCNA). Hub genes associated with periodontitis were identified for subsequent functional enrichment and pathway analysis through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The diagnostic performance of predictive models for the five most significant hub genes was assessed using receiver operating characteristic (ROC) curves. Finally, we performed Mendelian randomization analysis to evaluate the genetic causal links between the hub genes and periodontitis.

Results

By intersecting WGCNA’s most relevant module genes with significantly differentially expressed genes, we identified 98 hub genes. GO and KEGG analyses underscored the roles of these hub genes in immune cell activation, cytokine signaling, and inflammation. Cytoscape analysis of the top five hub genes, including CXCR4, CD19, CD27, FCGR3B, and CD79A, was conducted. ROC analysis demonstrated excellent performance of the linear predictor model in predicting the risk of periodontitis. Through the application of the inverse variance weighted (IVW) approach, our analysis revealed that the central gene CD27 is linked to periodontitis (OR = 0.7536, 95%CI = 0.5886–0.9647, p = 0.02477).

Conclusion

Our analysis established a genetic link between the CD27 gene and periodontitis, indicating its potential as a diagnostic or therapeutic target.

牙周炎是一种慢性炎症性疾病,会损害牙齿周围的软组织和骨骼。影响成年人,轻度牙周炎很常见,而严重病例影响多达20%的个体,患病率为45%-50%。本研究旨在通过生物信息学方法鉴定和分析牙周炎中差异表达基因的功能。此外,我们旨在通过孟德尔随机化验证这些基因与牙周炎的因果关系。方法选取GEO数据库中210例牙周炎患者的557份样本,重点分析基因差异表达,并进行加权基因共表达网络分析(WGCNA)。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)鉴定出与牙周炎相关的枢纽基因,并进行后续功能富集和途径分析。使用受试者工作特征(ROC)曲线评估预测模型对5个最重要枢纽基因的诊断性能。最后,我们进行孟德尔随机化分析来评估中枢基因与牙周炎之间的遗传因果关系。结果通过将WGCNA最相关的模块基因与显著差异表达基因交叉,鉴定出98个枢纽基因。GO和KEGG分析强调了这些中心基因在免疫细胞激活、细胞因子信号传导和炎症中的作用。对前5个中心基因CXCR4、CD19、CD27、FCGR3B和CD79A进行细胞景观分析。ROC分析显示线性预测模型在预测牙周炎风险方面表现优异。通过应用逆方差加权(IVW)方法,我们的分析显示中心基因CD27与牙周炎有关(OR = 0.7536, 95%CI = 0.5886-0.9647, p = 0.02477)。结论我们的分析建立了CD27基因与牙周炎之间的遗传联系,表明其作为诊断或治疗靶点的潜力。
{"title":"Identification of Key Periodontitis Genes and Their Mechanisms of Action Using Comprehensive Multiple Microarray Analysis and Mendelian Randomization Methods","authors":"Kezhen Xiang,&nbsp;Conghua Li,&nbsp;Na Hu","doi":"10.1155/ijog/5587468","DOIUrl":"https://doi.org/10.1155/ijog/5587468","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Periodontitis, a chronic inflammatory disease, damages the soft tissues and bones around the teeth. Affecting adults, mild periodontitis is common, while severe cases impact up to 20% of individuals, with a prevalence of 45%–50%. This study was aimed at identifying and analyzing the functions of genes differentially expressed in periodontitis through bioinformatics. Additionally, we aimed to validate the causal relationships of these genes with periodontitis using Mendelian randomization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The investigation included 557 samples obtained from 210 patients suffering from periodontitis within the GEO database, focusing on the differential expression of genes and conducting a weighted gene coexpression network analysis (WGCNA). Hub genes associated with periodontitis were identified for subsequent functional enrichment and pathway analysis through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The diagnostic performance of predictive models for the five most significant hub genes was assessed using receiver operating characteristic (ROC) curves. Finally, we performed Mendelian randomization analysis to evaluate the genetic causal links between the hub genes and periodontitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By intersecting WGCNA’s most relevant module genes with significantly differentially expressed genes, we identified 98 hub genes. GO and KEGG analyses underscored the roles of these hub genes in immune cell activation, cytokine signaling, and inflammation. Cytoscape analysis of the top five hub genes, including CXCR4, CD19, CD27, FCGR3B, and CD79A, was conducted. ROC analysis demonstrated excellent performance of the linear predictor model in predicting the risk of periodontitis. Through the application of the inverse variance weighted (IVW) approach, our analysis revealed that the central gene CD27 is linked to periodontitis (OR = 0.7536, 95<i>%</i>CI = 0.5886–0.9647, <i>p</i> = 0.02477).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our analysis established a genetic link between the CD27 gene and periodontitis, indicating its potential as a diagnostic or therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5587468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366544","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}
引用次数: 0
Identification of Core Senescence-Related Genes and Characterization of Comprehensive Immune Landscape in Intervertebral Disc Degeneration 椎间盘退变中核心衰老相关基因的鉴定和综合免疫景观的表征。
Pub Date : 2025-10-22 DOI: 10.1155/ijog/2521994
Qiang Xu, Zeshuang Lian, Aoting Wang, Ding Li, Ye Wang, Yu Guo, Jialin Qin, Junfang Wang

Background

Intervertebral disc degeneration (IVDD) is a musculoskeletal degenerative disease closely associated with age and immunoreaction. However, the mechanism of senescence and immune infiltration landscape in IVDD is still unclear. Our study was aimed at investigating the pivotal senescence-related genes (SRGs) and immune cells involved in IVDD.

Methods

We downloaded expression profiles by array from the GEO database and obtained 543 human SRGs from the Human Aging Genomic Resources (HAGR). Differentially expressed gene analysis, GO, KEGG, PPI network analysis, etc., were used to identify senescence-related differentially expressed genes (SRDEGs). We then used WGCNA and machine learning algorithms to explore hub genes and validated the reliability of the results in single-cell RNA sequencing (scRNA-seq) and cell models.

Results

We identified a core senescence-associated differentially expressed gene, connective tissue growth factor (CTGF). RNA sequencing revealed significantly upregulated CTGF expression in the degenerative group, a finding consistently validated by both scRNA-seq and in vitro models. CTGF demonstrated promising diagnostic value for IVDD in risk prediction and clinical detection (AUC: 0.8361, 95% CI: 0.668–0.9953). Furthermore, we observed endothelial cells, smooth muscle cells, and erythrocytes within disc tissues, suggesting postdegenerative vascular invasion into the nucleus pulposus. Notably, immune cell infiltration, including B cells, T cells, plasma cells, and macrophages, was detected in both mildly and severely degenerated nucleus pulposus tissues, with a significantly higher abundance of immune cells in the mild degenerative group compared to severe cases.

Conclusion

CTGF may play a pivotal role in IVDD, advancing our understanding of disease pathogenesis and demonstrating potential as a diagnostic and therapeutic target. Notably, reduced immune cell infiltration in severe IVDD may stem from either activation of intrinsic repair mechanisms or an immune-exhausted state. Investigating dynamic alterations in immune cell populations during IVDD progression could elucidate the critical role of immunity in disease pathogenesis and inform novel strategies for diagnosis and therapeutic intervention.

背景:椎间盘退变(IVDD)是一种与年龄和免疫反应密切相关的肌肉骨骼退行性疾病。然而,IVDD的衰老机制和免疫浸润景观尚不清楚。我们的研究旨在探讨关键衰老相关基因(SRGs)和免疫细胞参与IVDD。方法:从GEO数据库中通过阵列下载表达谱,从人类衰老基因组资源(HAGR)中获取543个人类srg。采用差异表达基因分析、GO、KEGG、PPI网络分析等方法鉴定衰老相关差异表达基因(SRDEGs)。然后,我们使用WGCNA和机器学习算法来探索中心基因,并在单细胞RNA测序(scRNA-seq)和细胞模型中验证结果的可靠性。结果:我们确定了一个核心衰老相关的差异表达基因,结缔组织生长因子(CTGF)。RNA测序显示,在退行性组织中,CTGF表达显著上调,这一发现得到了scRNA-seq和体外模型的一致证实。CTGF在IVDD的风险预测和临床检测方面具有良好的诊断价值(AUC: 0.8361, 95% CI: 0.668-0.9953)。此外,我们在椎间盘组织中观察到内皮细胞、平滑肌细胞和红细胞,提示退行性变后血管侵入髓核。值得注意的是,在轻度和重度退行性髓核组织中均检测到免疫细胞浸润,包括B细胞、T细胞、浆细胞和巨噬细胞,轻度退行性髓核组的免疫细胞丰度明显高于重度髓核组。结论:CTGF可能在IVDD中发挥关键作用,促进了我们对疾病发病机制的认识,并显示出作为诊断和治疗靶点的潜力。值得注意的是,在严重的IVDD中,免疫细胞浸润减少可能源于内在修复机制的激活或免疫耗尽状态。研究IVDD进展过程中免疫细胞群的动态变化可以阐明免疫在疾病发病机制中的关键作用,并为诊断和治疗干预提供新的策略。
{"title":"Identification of Core Senescence-Related Genes and Characterization of Comprehensive Immune Landscape in Intervertebral Disc Degeneration","authors":"Qiang Xu,&nbsp;Zeshuang Lian,&nbsp;Aoting Wang,&nbsp;Ding Li,&nbsp;Ye Wang,&nbsp;Yu Guo,&nbsp;Jialin Qin,&nbsp;Junfang Wang","doi":"10.1155/ijog/2521994","DOIUrl":"10.1155/ijog/2521994","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a musculoskeletal degenerative disease closely associated with age and immunoreaction. However, the mechanism of senescence and immune infiltration landscape in IVDD is still unclear. Our study was aimed at investigating the pivotal senescence-related genes (SRGs) and immune cells involved in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We downloaded expression profiles by array from the GEO database and obtained 543 human SRGs from the Human Aging Genomic Resources (HAGR). Differentially expressed gene analysis, GO, KEGG, PPI network analysis, etc., were used to identify senescence-related differentially expressed genes (SRDEGs). We then used WGCNA and machine learning algorithms to explore hub genes and validated the reliability of the results in single-cell RNA sequencing (scRNA-seq) and cell models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a core senescence-associated differentially expressed gene, connective tissue growth factor (CTGF). RNA sequencing revealed significantly upregulated CTGF expression in the degenerative group, a finding consistently validated by both scRNA-seq and in vitro models. CTGF demonstrated promising diagnostic value for IVDD in risk prediction and clinical detection (AUC: 0.8361, 95% CI: 0.668–0.9953). Furthermore, we observed endothelial cells, smooth muscle cells, and erythrocytes within disc tissues, suggesting postdegenerative vascular invasion into the nucleus pulposus. Notably, immune cell infiltration, including B cells, T cells, plasma cells, and macrophages, was detected in both mildly and severely degenerated nucleus pulposus tissues, with a significantly higher abundance of immune cells in the mild degenerative group compared to severe cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CTGF may play a pivotal role in IVDD, advancing our understanding of disease pathogenesis and demonstrating potential as a diagnostic and therapeutic target. Notably, reduced immune cell infiltration in severe IVDD may stem from either activation of intrinsic repair mechanisms or an immune-exhausted state. Investigating dynamic alterations in immune cell populations during IVDD progression could elucidate the critical role of immunity in disease pathogenesis and inform novel strategies for diagnosis and therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354475","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}
引用次数: 0
Exploration of the Mechanism of Tongmai Xianxiang in Treating Postherpetic Neuralgia Based on Gas Chromatography–Mass Spectrometry Analysis and Network Pharmacology 基于气相色谱-质谱联用及网络药理学研究通脉仙香治疗疱疹后神经痛的作用机制。
Pub Date : 2025-10-21 DOI: 10.1155/ijog/7415848
Linglong Qu, Hui Wang, Yufeng Huang, Zhen Gao, Ruichang Song, Shiyu Sun, Pingping Shao, Rukai Wang, Chunlin Li

Objective

The aim of this study is to explore the potential target of Tongmai Xianxiang in the prevention and treatment of postherpetic neuralgia (PHN) by gas chromatography–mass spectrometry (GC-MS) and network pharmacology.

Methods

Quantitative analysis using GC-MS was employed to obtain the chemical components of Tongmai Xianxiang, and target site prediction was conducted; PHN-related targets were collected from relevant disease databases; the anti-PHN targets of Tongmai Xianxiang were obtained through network pharmacology methods, and molecular docking was performed on the main targets.

Results

A total of 633 active components were screened by GC-MS, corresponding to 772 targets. By searching the disease database, a total of 169 PHN-related disease targets were obtained after removing duplicates. A total of 53 core genes, including SLC6A4, MAOA, DRD2, and ALB, were obtained by intersecting the corresponding target and PHN target. Through molecular docking, the results indicate that ALB has the lowest free binding energy with Z-butylidenephthalide, 2-undecanol, and 1,6,10-dodecatrien-3-OL, 3,7,11-trimethyl-, (E)-.

Conclusion

Tongmai Xianxiang can prevent PHN by multitarget, multiprocess, and multipathway. This study provides new ideas and new targets for the intervention of Tongmai Xianxiang in PHN.

目的:采用气相色谱-质谱联用技术和网络药理学方法,探讨通脉仙香防治带状疱疹后神经痛(PHN)的潜在靶点。方法:采用气相色谱-质谱法进行定量分析,获得通脉鲜香的化学成分,并进行靶位预测;从相关疾病数据库中收集phn相关靶点;通过网络药理学方法获得通脉仙香抗phn靶点,并对主要靶点进行分子对接。结果:GC-MS共筛选出633个有效成分,对应772个靶点。通过对疾病数据库的检索,剔除重复项后,共获得169个phn相关疾病靶点。将相应的靶点与PHN靶点相交,共获得SLC6A4、MAOA、DRD2、ALB等53个核心基因。通过分子对接,结果表明ALB与z -丁基酞、2-十一醇、1,6,10-十二癸烯-3-醇、3,7,11-三甲基、(E)-的自由结合能最低。结论:通脉鲜香具有多靶点、多过程、多途径的预防PHN作用。本研究为通脉鲜香干预PHN提供了新思路和新靶点。
{"title":"Exploration of the Mechanism of Tongmai Xianxiang in Treating Postherpetic Neuralgia Based on Gas Chromatography–Mass Spectrometry Analysis and Network Pharmacology","authors":"Linglong Qu,&nbsp;Hui Wang,&nbsp;Yufeng Huang,&nbsp;Zhen Gao,&nbsp;Ruichang Song,&nbsp;Shiyu Sun,&nbsp;Pingping Shao,&nbsp;Rukai Wang,&nbsp;Chunlin Li","doi":"10.1155/ijog/7415848","DOIUrl":"10.1155/ijog/7415848","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study is to explore the potential target of Tongmai Xianxiang in the prevention and treatment of postherpetic neuralgia (PHN) by gas chromatography–mass spectrometry (GC-MS) and network pharmacology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Quantitative analysis using GC-MS was employed to obtain the chemical components of Tongmai Xianxiang, and target site prediction was conducted; PHN-related targets were collected from relevant disease databases; the anti-PHN targets of Tongmai Xianxiang were obtained through network pharmacology methods, and molecular docking was performed on the main targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 633 active components were screened by GC-MS, corresponding to 772 targets. By searching the disease database, a total of 169 PHN-related disease targets were obtained after removing duplicates. A total of 53 core genes, including SLC6A4, MAOA, DRD2, and ALB, were obtained by intersecting the corresponding target and PHN target. Through molecular docking, the results indicate that ALB has the lowest free binding energy with Z-butylidenephthalide, 2-undecanol, and 1,6,10-dodecatrien-3-OL, 3,7,11-trimethyl-, (E)-.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tongmai Xianxiang can prevent PHN by multitarget, multiprocess, and multipathway. This study provides new ideas and new targets for the intervention of Tongmai Xianxiang in PHN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344881","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}
引用次数: 0
Identifying the Key Mitochondria-Related Genes in COPD by Integrating Machine Learning and Bioinformatics Analyses 通过整合机器学习和生物信息学分析鉴定COPD的关键线粒体相关基因。
Pub Date : 2025-10-21 DOI: 10.1155/ijog/7060748
Jiajia Qu, Mengyu Zhang, Yajie Hu, Guang Yang, Xiaoning Zhang, Wenqing Zhang, Yiqing Qu

Background

Chronic obstructive pulmonary disease (COPD), a prevalent chronic respiratory disorder with high morbidity and mortality, is closely associated with mitochondrial dysfunction and immune dysregulation; however, the underlying mechanisms remain unclear.

Aims

The aim of this study is to identify mitochondrial hub genes and evaluate their diagnostic potential in COPD.

Methods

This study combined bioinformatics and experimental methods to investigate mitochondria-related differentially expressed genes (MitoDEGs) in COPD pathogenesis. Two GEO datasets (GSE38974/GSE8545) were analyzed to identify MitoDEGs, which were functionally characterized and refined via machine learning (LASSO/SVM-RFE). Key genes were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in bronchial epithelial cells and COPD mouse model lung tissues. Immune infiltration analysis revealed connections between MitoDEGs and immune dysregulation in COPD that were experimentally confirmed using immunohistochemistry (IHC) and immunofluorescence (IF).

Results

Among 28 identified MitoDEGs, five feature genes (BAX, DLST, FKBP10, FUNDC2, and RMDN1) were selected. Subsequent validation through qRT-PCR, Western blot, and ROC curve further confirmed BAX and DLST as core hub genes. Immune profiling revealed significantly increased M0 macrophage infiltration and reduced activated NK cells in COPD. BAX and DLST expression was positively correlated with M0 macrophages but negatively with activated NK cells, a finding corroborated by IHC and IF assays.

Conclusions

These findings highlight BAX and DLST as potential mitochondrial dysfunction biomarkers in COPD, linking their roles to immune cell infiltration. This study provides novel insights into cigarette smoke-induced COPD pathogenesis and underscores the diagnostic utility of targeting mitochondrial–immune interactions.

背景:慢性阻塞性肺疾病(COPD)是一种常见的慢性呼吸系统疾病,发病率和死亡率高,与线粒体功能障碍和免疫失调密切相关;然而,潜在的机制仍不清楚。目的:本研究的目的是鉴定线粒体中心基因并评估其在COPD中的诊断潜力。方法:本研究结合生物信息学和实验方法,探讨线粒体相关差异表达基因(MitoDEGs)在COPD发病机制中的作用。通过分析两个GEO数据集(GSE38974/GSE8545)来识别mitodeg,并通过机器学习(LASSO/SVM-RFE)对其进行功能表征和改进。在支气管上皮细胞和COPD小鼠模型肺组织中,采用定量实时聚合酶链反应(qRT-PCR)和Western blot进一步验证关键基因。免疫浸润分析揭示了mitodeg与COPD免疫失调之间的联系,并通过免疫组织化学(IHC)和免疫荧光(IF)实验证实了这一点。结果:在鉴定到的28个mitodeg中,筛选出5个特征基因(BAX、DLST、FKBP10、FUNDC2、RMDN1)。随后通过qRT-PCR、Western blot和ROC曲线验证,进一步证实BAX和DLST为核心枢纽基因。免疫分析显示慢性阻塞性肺病患者M0巨噬细胞浸润显著增加,活化NK细胞显著减少。BAX和DLST的表达与M0巨噬细胞呈正相关,而与活化的NK细胞呈负相关,IHC和IF实验证实了这一发现。结论:这些发现强调BAX和DLST是COPD中潜在的线粒体功能障碍生物标志物,将它们的作用与免疫细胞浸润联系起来。这项研究为香烟烟雾诱导的COPD发病机制提供了新的见解,并强调了靶向线粒体-免疫相互作用的诊断效用。
{"title":"Identifying the Key Mitochondria-Related Genes in COPD by Integrating Machine Learning and Bioinformatics Analyses","authors":"Jiajia Qu,&nbsp;Mengyu Zhang,&nbsp;Yajie Hu,&nbsp;Guang Yang,&nbsp;Xiaoning Zhang,&nbsp;Wenqing Zhang,&nbsp;Yiqing Qu","doi":"10.1155/ijog/7060748","DOIUrl":"10.1155/ijog/7060748","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD), a prevalent chronic respiratory disorder with high morbidity and mortality, is closely associated with mitochondrial dysfunction and immune dysregulation; however, the underlying mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study is to identify mitochondrial hub genes and evaluate their diagnostic potential in COPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study combined bioinformatics and experimental methods to investigate mitochondria-related differentially expressed genes (MitoDEGs) in COPD pathogenesis. Two GEO datasets (GSE38974/GSE8545) were analyzed to identify MitoDEGs, which were functionally characterized and refined via machine learning (LASSO/SVM-RFE). Key genes were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in bronchial epithelial cells and COPD mouse model lung tissues. Immune infiltration analysis revealed connections between MitoDEGs and immune dysregulation in COPD that were experimentally confirmed using immunohistochemistry (IHC) and immunofluorescence (IF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 28 identified MitoDEGs, five feature genes (<i>BAX</i>, <i>DLST</i>, <i>FKBP10</i>, <i>FUNDC2</i>, and <i>RMDN1</i>) were selected. Subsequent validation through qRT-PCR, Western blot, and ROC curve further confirmed <i>BAX</i> and <i>DLST</i> as core hub genes. Immune profiling revealed significantly increased M0 macrophage infiltration and reduced activated NK cells in COPD. BAX and DLST expression was positively correlated with M0 macrophages but negatively with activated NK cells, a finding corroborated by IHC and IF assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight <i>BAX</i> and <i>DLST</i> as potential mitochondrial dysfunction biomarkers in COPD, linking their roles to immune cell infiltration. This study provides novel insights into cigarette smoke-induced COPD pathogenesis and underscores the diagnostic utility of targeting mitochondrial–immune interactions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344863","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}
引用次数: 0
Single-Cell Sequencing Redefines Immune Heterogeneity and Communication Networks in ARDS: Toward Precision Therapeutics 单细胞测序重新定义了ARDS的免疫异质性和通讯网络:走向精确治疗。
Pub Date : 2025-10-21 DOI: 10.1155/ijog/9902676
Han-Bing Chen, An-Min Xu, Hai-Bo Qiu, Jie Chao

Acute respiratory distress syndrome (ARDS) is a critical condition characterized by diffuse alveolar damage and intense inflammatory responses. During the COVID-19 pandemic, its incidence and mortality have remained persistently high. Conventional approaches have struggled to uncover the complex cellular heterogeneity and dynamic inflammatory networks underlying ARDS. The advent of single-cell sequencing technologies has revolutionized our ability to dissect the molecular mechanisms of ARDS. This review systematically summarizes recent advances in the application of single-cell sequencing in studying pulmonary inflammation in ARDS, with a focus on its strengths in elucidating immune cell heterogeneity, reconstructing intercellular communication networks, and identifying potential therapeutic targets. Furthermore, we discuss current technical limitations and translational challenges, aiming to provide a theoretical foundation and future direction for translating mechanistic insights into precision medicine for ARDS.

急性呼吸窘迫综合征(ARDS)是一种以弥漫性肺泡损伤和强烈炎症反应为特征的危重疾病。在2019冠状病毒病大流行期间,其发病率和死亡率一直居高不下。传统方法难以揭示ARDS背后复杂的细胞异质性和动态炎症网络。单细胞测序技术的出现彻底改变了我们解剖ARDS分子机制的能力。本文系统总结了单细胞测序在ARDS肺部炎症研究中的最新进展,重点介绍了单细胞测序在阐明免疫细胞异质性、重建细胞间通讯网络和识别潜在治疗靶点方面的优势。此外,我们还讨论了目前的技术限制和转化挑战,旨在为将机制见解转化为ARDS的精准医学提供理论基础和未来方向。
{"title":"Single-Cell Sequencing Redefines Immune Heterogeneity and Communication Networks in ARDS: Toward Precision Therapeutics","authors":"Han-Bing Chen,&nbsp;An-Min Xu,&nbsp;Hai-Bo Qiu,&nbsp;Jie Chao","doi":"10.1155/ijog/9902676","DOIUrl":"10.1155/ijog/9902676","url":null,"abstract":"<p>Acute respiratory distress syndrome (ARDS) is a critical condition characterized by diffuse alveolar damage and intense inflammatory responses. During the COVID-19 pandemic, its incidence and mortality have remained persistently high. Conventional approaches have struggled to uncover the complex cellular heterogeneity and dynamic inflammatory networks underlying ARDS. The advent of single-cell sequencing technologies has revolutionized our ability to dissect the molecular mechanisms of ARDS. This review systematically summarizes recent advances in the application of single-cell sequencing in studying pulmonary inflammation in ARDS, with a focus on its strengths in elucidating immune cell heterogeneity, reconstructing intercellular communication networks, and identifying potential therapeutic targets. Furthermore, we discuss current technical limitations and translational challenges, aiming to provide a theoretical foundation and future direction for translating mechanistic insights into precision medicine for ARDS.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344989","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}
引用次数: 0
A Novel Signature of Disulfidptosis-Related lncRNAs Predicts Prognosis in Glioma: Evidence From Bioinformatic Analysis and Experiments 一种新的双硫中毒相关lncrna信号预测胶质瘤预后:来自生物信息学分析和实验的证据。
Pub Date : 2025-10-13 DOI: 10.1155/ijog/5573323
Taiyao Li, Ying Cao, Jie Wang, Xiaoyuan Tian, Bin Dong, Yanqin Yang

Glioma is the most common primary malignant brain tumor, characterized by high mortality and poor prognosis. Disulfidptosis, a recently identified form of regulated cell death, has been implicated in tumor progression; however, its role in glioma remains unclear. In this study, we developed and validated a novel prognostic signature based on disulfidptosis-related long noncoding RNAs (DRLs) by integrating transcriptomic and clinical data from The Cancer Genome Atlas. Seven DRLs were identified to construct a risk model that effectively stratified patients into high- and low-risk groups with significantly different overall survival outcomes. Functional enrichment and immune-related analyses revealed that the high-risk group exhibited distinct immune microenvironment features, including altered immune cell infiltration, immune checkpoint expression, and activity of immune-related pathways, suggesting a potential link between DRLs and immune modulation. Drug sensitivity analysis identified several chemotherapeutic agents and targeted inhibitors with higher predicted efficacy in the high-risk group, offering insights into personalized treatment strategies. In vitro experiments further demonstrated that LINC02542 knockdown significantly suppressed glioma cell proliferation, migration, and invasion. Collectively, these findings indicate that the DRL signature functions as an independent prognostic indicator and a potential biomarker for immune landscape profiling and immunotherapy response prediction in glioma. This integrative multiomics approach provides novel perspectives for precision immunotherapy and targeted therapy in glioma.

胶质瘤是最常见的原发性恶性脑肿瘤,病死率高,预后差。最近发现的一种受调节的细胞死亡形式——双侧下垂与肿瘤进展有关;然而,它在神经胶质瘤中的作用尚不清楚。在这项研究中,我们通过整合来自癌症基因组图谱的转录组学和临床数据,开发并验证了一种基于二硫裂相关长链非编码rna (drl)的新型预后特征。确定了7个drl,构建了一个风险模型,有效地将患者分为高风险和低风险组,总体生存结果存在显著差异。功能富集和免疫相关分析显示,高危组表现出明显的免疫微环境特征,包括免疫细胞浸润、免疫检查点表达和免疫相关途径的活性改变,这表明drl与免疫调节之间存在潜在联系。药物敏感性分析确定了几种化疗药物和靶向抑制剂在高危人群中具有较高的预测疗效,为个性化治疗策略提供了见解。体外实验进一步证明,敲低LINC02542可显著抑制胶质瘤细胞的增殖、迁移和侵袭。综上所述,这些发现表明DRL特征作为一种独立的预后指标和潜在的生物标志物,可用于胶质瘤的免疫景观分析和免疫治疗反应预测。这种综合多组学方法为神经胶质瘤的精确免疫治疗和靶向治疗提供了新的视角。
{"title":"A Novel Signature of Disulfidptosis-Related lncRNAs Predicts Prognosis in Glioma: Evidence From Bioinformatic Analysis and Experiments","authors":"Taiyao Li,&nbsp;Ying Cao,&nbsp;Jie Wang,&nbsp;Xiaoyuan Tian,&nbsp;Bin Dong,&nbsp;Yanqin Yang","doi":"10.1155/ijog/5573323","DOIUrl":"10.1155/ijog/5573323","url":null,"abstract":"<p>Glioma is the most common primary malignant brain tumor, characterized by high mortality and poor prognosis. Disulfidptosis, a recently identified form of regulated cell death, has been implicated in tumor progression; however, its role in glioma remains unclear. In this study, we developed and validated a novel prognostic signature based on disulfidptosis-related long noncoding RNAs (DRLs) by integrating transcriptomic and clinical data from The Cancer Genome Atlas. Seven DRLs were identified to construct a risk model that effectively stratified patients into high- and low-risk groups with significantly different overall survival outcomes. Functional enrichment and immune-related analyses revealed that the high-risk group exhibited distinct immune microenvironment features, including altered immune cell infiltration, immune checkpoint expression, and activity of immune-related pathways, suggesting a potential link between DRLs and immune modulation. Drug sensitivity analysis identified several chemotherapeutic agents and targeted inhibitors with higher predicted efficacy in the high-risk group, offering insights into personalized treatment strategies. In vitro experiments further demonstrated that LINC02542 knockdown significantly suppressed glioma cell proliferation, migration, and invasion. Collectively, these findings indicate that the DRL signature functions as an independent prognostic indicator and a potential biomarker for immune landscape profiling and immunotherapy response prediction in glioma. This integrative multiomics approach provides novel perspectives for precision immunotherapy and targeted therapy in glioma.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291879","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}
引用次数: 0
Growth Hormone Alleviates Atherosclerosis Through Regulating the Activity of PI3K/AKT Pathway: Insights From Single-Cell Sequence and Mechanism Exploration 生长激素通过调节PI3K/AKT通路活性缓解动脉粥样硬化:来自单细胞序列和机制探索的见解
Pub Date : 2025-10-13 DOI: 10.1155/ijog/9710652
Jin Cai, Shuang Shi, Yuhang Wang, Xiangdong Zhang, Xinghua Wei, Yanjing Wu, Yunlong Shi, Bin Li, Daorong Hou
<div> <section> <h3> Purpose</h3> <p>This research sought to investigate the impact and underlying mechanisms of growth hormone (GH) on atherosclerosis (AS) based on the analysis of single-cell RNA sequencing (scRNA-seq) data.</p> </section> <section> <h3> Methods</h3> <p>We analyzed the impact of GH on arterial vascular smooth muscle cells (VSMCs) by utilizing scRNA-seq data obtained from both atherosclerotic and healthy vascular tissues in mice. AS was induced in C57BL/6 and ApoE<sup>−/−</sup> mice through hypophysectomy performed via the parapharyngeal approach, followed by a high-fat diet (HFD), resulting in the C57-Hx and ApoE<sup>−/−</sup>-Hx models. AS was evaluated by measuring arterial lipid deposition, plaque progression, collagen loss, vascular inflammation, and oxidative stress. Serum metabolite alterations were assessed using liquid chromatography-mass spectrometry (LC-MS). RNA sequencing was employed to examine the underlying mechanisms of GH in the context of AS treatment, with findings further confirmed through western blot analysis. In vitro experiments involved treating VSMCs with oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerotic injury. The formation of foam cells was evaluated by measuring lipid accumulation, inflammatory responses, apoptosis, and the expression levels of foam cell-related markers. Finally, the PI3K/AKT inhibitor LY294002 confirmed that GH alleviates AS via the PI3K/AKT signaling pathway.</p> </section> <section> <h3> Results</h3> <p>scRNA-seq data analysis showed that growth hormone signaling was reduced in VSMCs of atherosclerotic arteries. HFD led to elevated levels of serum total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), accompanied by increased lipid deposition, inflammatory responses, and oxidative stress. In contrast, high-density lipoprotein cholesterol (HDL-C) and insulin-like growth factor 1 (IGF-1) levels were lower in C57-Hx mice. GH treatment improved HFD-induced AS in ApoE<sup>−/−</sup>-Hx mice. LC-MS analysis revealed that GH altered lipid metabolism in serum samples from C57-sham, C57-Hx, ApoE<sup>−/−</sup>-Hx, and ApoE<sup>−/−</sup>-Hx-GH(3) mice. GH maintained lipid balance by increasing 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), PE-NMe2(18:1(9z)/18:1(9z)) (DMPE), and 4-chloro-2-nitrobenzylalcohol levels and decreasing 1-heptadecanoyl-sn-glycerol-3-phosphocholine. RNA sequencing showed significant gene expression differences in the aortas of C57-sham and C57-Hx mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that GH inhibited the progression of AS by modulating the phosphatidylinositol 3-kinase/pr
目的:本研究旨在通过单细胞RNA测序(scRNA-seq)数据分析,探讨生长激素(GH)对动脉粥样硬化(AS)的影响及其潜在机制。方法:利用小鼠动脉粥样硬化和健康血管组织的scRNA-seq数据,分析生长激素对动脉血管平滑肌细胞(VSMCs)的影响。在C57BL/6和ApoE-/-小鼠中,通过咽旁入路行垂体切除术,然后高脂饮食(HFD)诱导AS,得到C57-Hx和ApoE-/- Hx模型。通过测量动脉脂质沉积、斑块进展、胶原流失、血管炎症和氧化应激来评估AS。采用液相色谱-质谱法(LC-MS)评估血清代谢物的变化。我们利用RNA测序来研究生长激素在AS治疗中的潜在机制,并通过western blot分析进一步证实了这一发现。体外实验采用氧化低密度脂蛋白(ox-LDL)处理VSMCs,模拟动脉粥样硬化损伤。通过测量脂质积累、炎症反应、细胞凋亡和泡沫细胞相关标志物的表达水平来评估泡沫细胞的形成。最后,PI3K/AKT抑制剂LY294002证实GH通过PI3K/AKT信号通路缓解AS。结果:scRNA-seq数据分析显示,生长激素信号在动脉粥样硬化的VSMCs中减少。HFD导致血清总胆固醇(TC)、甘油三酯(tg)和低密度脂蛋白胆固醇(LDL-C)水平升高,并伴有脂质沉积、炎症反应和氧化应激增加。相比之下,C57-Hx小鼠的高密度脂蛋白胆固醇(HDL-C)和胰岛素样生长因子1 (IGF-1)水平较低。生长激素治疗可改善ApoE-/- Hx小鼠hfd诱导的AS。LC-MS分析显示,生长激素改变了C57-sham、C57-Hx、ApoE-/- Hx和ApoE-/- Hx-GH(3)小鼠血清样品中的脂质代谢。GH通过提高1-棕榈酰-2-油基-sn-甘油-3-磷胆碱(POPC)、PE-NMe2(18:1(9z)/18:1(9z)) (DMPE)和4-氯-2-硝基苯基醇水平,降低1-庚烷酰-sn-甘油-3-磷胆碱水平来维持脂质平衡。RNA测序显示C57-sham和C57-Hx小鼠主动脉基因表达差异显著。京都基因与基因组百科(KEGG)通路分析显示,生长激素通过调节磷脂酰肌醇3-激酶/蛋白激酶B (PI3K/AKT)信号通路抑制AS的进展,这一发现通过western blotting得到验证。进一步的体外研究表明,生长激素通过激活PI3K/AKT通路,对VSMCs对ox- ldl诱导的损伤具有保护作用,使用特异性PI3K抑制剂LY294002的实验证明了这一点。结论:生长激素通过激活PI3K/AKT通路缓解AS的发展。本研究结果强调了生长激素在抑制AS方面的治疗潜力,并强调了PI3K/AKT通路作为临床干预的一个有希望的靶点的重要性。
{"title":"Growth Hormone Alleviates Atherosclerosis Through Regulating the Activity of PI3K/AKT Pathway: Insights From Single-Cell Sequence and Mechanism Exploration","authors":"Jin Cai,&nbsp;Shuang Shi,&nbsp;Yuhang Wang,&nbsp;Xiangdong Zhang,&nbsp;Xinghua Wei,&nbsp;Yanjing Wu,&nbsp;Yunlong Shi,&nbsp;Bin Li,&nbsp;Daorong Hou","doi":"10.1155/ijog/9710652","DOIUrl":"10.1155/ijog/9710652","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Purpose&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This research sought to investigate the impact and underlying mechanisms of growth hormone (GH) on atherosclerosis (AS) based on the analysis of single-cell RNA sequencing (scRNA-seq) data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We analyzed the impact of GH on arterial vascular smooth muscle cells (VSMCs) by utilizing scRNA-seq data obtained from both atherosclerotic and healthy vascular tissues in mice. AS was induced in C57BL/6 and ApoE&lt;sup&gt;−/−&lt;/sup&gt; mice through hypophysectomy performed via the parapharyngeal approach, followed by a high-fat diet (HFD), resulting in the C57-Hx and ApoE&lt;sup&gt;−/−&lt;/sup&gt;-Hx models. AS was evaluated by measuring arterial lipid deposition, plaque progression, collagen loss, vascular inflammation, and oxidative stress. Serum metabolite alterations were assessed using liquid chromatography-mass spectrometry (LC-MS). RNA sequencing was employed to examine the underlying mechanisms of GH in the context of AS treatment, with findings further confirmed through western blot analysis. In vitro experiments involved treating VSMCs with oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerotic injury. The formation of foam cells was evaluated by measuring lipid accumulation, inflammatory responses, apoptosis, and the expression levels of foam cell-related markers. Finally, the PI3K/AKT inhibitor LY294002 confirmed that GH alleviates AS via the PI3K/AKT signaling pathway.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;scRNA-seq data analysis showed that growth hormone signaling was reduced in VSMCs of atherosclerotic arteries. HFD led to elevated levels of serum total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), accompanied by increased lipid deposition, inflammatory responses, and oxidative stress. In contrast, high-density lipoprotein cholesterol (HDL-C) and insulin-like growth factor 1 (IGF-1) levels were lower in C57-Hx mice. GH treatment improved HFD-induced AS in ApoE&lt;sup&gt;−/−&lt;/sup&gt;-Hx mice. LC-MS analysis revealed that GH altered lipid metabolism in serum samples from C57-sham, C57-Hx, ApoE&lt;sup&gt;−/−&lt;/sup&gt;-Hx, and ApoE&lt;sup&gt;−/−&lt;/sup&gt;-Hx-GH(3) mice. GH maintained lipid balance by increasing 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), PE-NMe2(18:1(9z)/18:1(9z)) (DMPE), and 4-chloro-2-nitrobenzylalcohol levels and decreasing 1-heptadecanoyl-sn-glycerol-3-phosphocholine. RNA sequencing showed significant gene expression differences in the aortas of C57-sham and C57-Hx mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that GH inhibited the progression of AS by modulating the phosphatidylinositol 3-kinase/pr","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292008","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}
引用次数: 0
Antihypertensive Drugs and Dental Caries Risk: A Drug–Target Mendelian Randomization Analysis 抗高血压药物与龋齿风险:药物靶孟德尔随机化分析。
Pub Date : 2025-10-07 DOI: 10.1155/ijog/1612322
Wenbin Shi, Shuhua Liu, Xiuxia Wu, Wangsong Cheng, Xiqun Jia, Ziyang Hu

Introduction and Objectives

To address the clinical uncertainty surrounding the effect of antihypertensive drugs on dental caries, this study was aimed at investigating the causal relationships between antihypertensive medication use and the risk of dental caries, utilizing a drug–target Mendelian randomization (MR) approach.

Methods

Nine antihypertensive drug classes′ influences on dental caries risk in the UK Biobank and FinnGen populations were assessed using drug–target MR. This genetic method utilizes randomly allocated gene variants as proxies for drug exposure, minimizing the confounding biases inherent in observational studies and allowing for more robust causal inference. Genetic variants associated with systolic blood pressure near the drug target genes were used to proxy for medication effects.

Results

In the FinnGen cohort, genetic analysis linked calcium channel blockers to a 3.3% reduction in dental caries risk (OR: 0.967, 95% CI: 0.949–0.985) and loop diuretics to a 6.9% reduction (OR: 0.931, 95% CI: 0.897–0.966). Conversely, aldosterone antagonists were suggestively associated with an 8.2% increased risk (OR: 1.082, 95% CI: 1.017–1.150). Notably, the protective trend for calcium channel blockers and loop diuretics was also observed in the UK Biobank. These findings, validated by eQTLs, highlight the impact of antihypertensive drugs on dental health.

Conclusion

The study suggests that calcium channel blockers and diuretics could potentially reduce the risk of dental caries. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of dental caries.

前言和目的:为了解决抗高血压药物对龋齿影响的临床不确定性,本研究旨在利用药物靶向孟德尔随机化(MR)方法调查抗高血压药物使用与龋齿风险之间的因果关系。方法:在UK Biobank和FinnGen人群中,使用药物靶向mr评估了九种抗高血压药物类别对龋齿风险的影响。这种遗传方法利用随机分配的基因变异作为药物暴露的代理,最大限度地减少了观察性研究中固有的混杂偏差,并允许更可靠的因果推断。药物靶基因附近与收缩压相关的遗传变异被用来替代药物效果。结果:在FinnGen队列中,遗传分析表明钙通道阻滞剂与龋齿风险降低3.3%相关(OR: 0.967, 95% CI: 0.949-0.985),袢利尿剂与龋齿风险降低6.9%相关(OR: 0.931, 95% CI: 0.897-0.966)。相反,醛固酮拮抗剂与8.2%的风险增加呈正相关(OR: 1.082, 95% CI: 1.017-1.150)。值得注意的是,钙通道阻滞剂和袢利尿剂的保护趋势在英国生物银行也被观察到。这些发现得到了等效qtl的验证,强调了抗高血压药物对牙齿健康的影响。结论:本研究提示钙通道阻滞剂和利尿剂可以潜在地降低龋齿的风险。需要进一步的研究来评估将降压药物用于预防龋齿的可行性。
{"title":"Antihypertensive Drugs and Dental Caries Risk: A Drug–Target Mendelian Randomization Analysis","authors":"Wenbin Shi,&nbsp;Shuhua Liu,&nbsp;Xiuxia Wu,&nbsp;Wangsong Cheng,&nbsp;Xiqun Jia,&nbsp;Ziyang Hu","doi":"10.1155/ijog/1612322","DOIUrl":"10.1155/ijog/1612322","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction and Objectives</h3>\u0000 \u0000 <p>To address the clinical uncertainty surrounding the effect of antihypertensive drugs on dental caries, this study was aimed at investigating the causal relationships between antihypertensive medication use and the risk of dental caries, utilizing a drug–target Mendelian randomization (MR) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine antihypertensive drug classes′ influences on dental caries risk in the UK Biobank and FinnGen populations were assessed using drug–target MR. This genetic method utilizes randomly allocated gene variants as proxies for drug exposure, minimizing the confounding biases inherent in observational studies and allowing for more robust causal inference. Genetic variants associated with systolic blood pressure near the drug target genes were used to proxy for medication effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the FinnGen cohort, genetic analysis linked calcium channel blockers to a 3.3% reduction in dental caries risk (OR: 0.967, 95% CI: 0.949–0.985) and loop diuretics to a 6.9% reduction (OR: 0.931, 95% CI: 0.897–0.966). Conversely, aldosterone antagonists were suggestively associated with an 8.2% increased risk (OR: 1.082, 95% CI: 1.017–1.150). Notably, the protective trend for calcium channel blockers and loop diuretics was also observed in the UK Biobank. These findings, validated by eQTLs, highlight the impact of antihypertensive drugs on dental health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study suggests that calcium channel blockers and diuretics could potentially reduce the risk of dental caries. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of dental caries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250971","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}
引用次数: 0
期刊
Comparative and Functional Genomics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1