Mammalian Genome最新文献

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Integrative multiomics elucidate crotonylation-associated GCDH in Parkinson's disease pathogenesis via metabolome remodeling. 整合多组学通过代谢组重塑阐明巴豆酰化相关GCDH在帕金森病发病机制中的作用。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-07-10 DOI: 10.1007/s00335-025-10151-x
Jia Fu, Jing Zhao, Na Mi, Chao Zhang, Yali Zhang, Lifen Yao
{"title":"Integrative multiomics elucidate crotonylation-associated GCDH in Parkinson's disease pathogenesis via metabolome remodeling.","authors":"Jia Fu, Jing Zhao, Na Mi, Chao Zhang, Yali Zhang, Lifen Yao","doi":"10.1007/s00335-025-10151-x","DOIUrl":"https://doi.org/10.1007/s00335-025-10151-x","url":null,"abstract":"<p><p>The pathophysiological significance of crotonylation and its metabolomic regulatory circuitry in Parkinson's disease (PD) remains elusive. We utilized Mendelian randomization (MR) frameworks combined with mediation analysis to establish causal links between crotonylation-associated genes and PD, while systematically delineating metabolite-mediated mechanisms. In this study, crotonylation-related genes were selected from the eQTLGen dataset, and their causal relationship with PD was assessed using two-sample MR analysis. Subsequently, we investigated metabolites associated with PD risk. Additionally, two-step MR and MR mediation analyses were applied to explore the mediating effects of crotonylation-related genes, metabolites, and PD. To further interpret cellular heterogeneity, publicly available GEO single-cell transcriptome data were integrated to analyze PD brain tissue dynamics and the regulatory mechanisms of key crotonylation-related genes. We identified 16 crotonylation-associated genes harboring cis-eQTLs, notably SIRT1, GCDH, and HDAC7, which demonstrated significant inverse associations with PD risk (p < 0.05). Through MR analysis, 74 PD-associated metabolites were identified. Mediation analysis further delineated GCDH-mediated PD risk reduction (β<sub>all</sub> = -0.054) through downregulation of X-21,471 and tetradecanedioate (C14-DC). Furthermore, single-cell transcriptomic analysis revealed that GCDH is predominantly and specifically highly expressed in astrocytes within PD brain tissues, and its dynamic regulatory pattern is closely linked to cell differentiation processes, suggesting a potential role in regulating PD pathogenesis via the NRG3-ERBB4 signaling axis. Our findings indicate that GCDH and its mediated metabolome critically contribute to PD pathogenesis, with astrocytes emerging as a central regulatory cell type. This study not only elucidates novel molecular landscapes underlying PD pathology but also highlights astrocytes as promising targets for therapeutic intervention.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple omics-based machine learning reveals peripheral blood immune cell landscape during acute rejection of kidney transplantation and constructs a precise non-invasive diagnostic strategy. 基于多组学的机器学习揭示肾移植急性排斥反应的外周血免疫细胞景观,构建精确的无创诊断策略。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-07-07 DOI: 10.1007/s00335-025-10149-5
Jiyue Wu, Lijian Gan, Xihao Shen, Feilong Zhang, Zhen Li, Huawei Cao, Hao Wang, Zejia Sun, Le Qi, Wei Wang
{"title":"Multiple omics-based machine learning reveals peripheral blood immune cell landscape during acute rejection of kidney transplantation and constructs a precise non-invasive diagnostic strategy.","authors":"Jiyue Wu, Lijian Gan, Xihao Shen, Feilong Zhang, Zhen Li, Huawei Cao, Hao Wang, Zejia Sun, Le Qi, Wei Wang","doi":"10.1007/s00335-025-10149-5","DOIUrl":"https://doi.org/10.1007/s00335-025-10149-5","url":null,"abstract":"<p><p>Kidney transplantation is the optimal treatment for end-stage renal disease (ESRD), but acute rejection (AR) remains a major factor affecting graft survival and patient prognosis. Currently, renal biopsy is the gold standard for diagnosing AR, but its invasiveness limits the application of dynamic monitoring. This study aims to analyze changes of immune cell and gene expression in the peripheral blood of AR recipients and construct a non-invasive AR diagnosis strategy. All datasets were downloaded from the GEO database. Single cells were annotated based on the expression profiles of surface proteins and changes of immune cell in the peripheral blood of AR and stable transplant (STA) recipients were compared. The high-dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm was used to analyze gene modules related to AR and to screen out hub genes by integrating bulk RNA-Seq. Based on hub genes, consensus clustering stratified recipients into two sub-clusters and a non-invasive AR diagnostic model was constructed using Convolutional Neural Networks (CNNs). Additionally, we also constructed a predictive model for long-term graft survival through combinations of 111 machine learning algorithms and validated the expression of hub genes in the rat AR model. AR recipients had higher abundance of memory B cells, effector memory T cells, terminally differentiated effector memory T cells (TEMRA), and NK T cells but lower Tregs in the peripheral blood compared to STA recipients. Through hdWGCNA analysis, we identified gene modules associated with these immune cells and screened out four hub immune-related genes (TBX21, CX3CR1, STAT1, and NKG7) after integrating bulk RNA-Seq. Based on these hub genes, recipients can be stratified into two sub-clusters with distinct clinical outcomes and biological characteristics. We also innovatively constructed a non-invasive AR diagnostic model using CNNs, which can effectively address the issues caused by batch effects and demonstrate a high diagnostic accuracy. Besides, the predictive model for long-term graft survival constructed using the RSF algorithm can divided recipients into high- and low-risk groups, with significantly higher rates of AR and long-term graft failed in the high-risk group. This study successfully identified immune cell subsets and hub genes related to AR. Based on hub genes, we successfully identified two distinct molecular sub-clusters of kidney transplant recipients, and constructed a non-invasive diagnostic model for AR and a predictive model for long-term graft survival. These models offer new tools for precise diagnosis and prognosis in kidney transplantation and may advance precision medicine.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-coverage whole-genome sequencing facilitates accurate and cost-effective haplotype reconstruction in complex mouse crosses. 低覆盖率全基因组测序有助于在复杂的小鼠杂交中精确和经济地重建单倍型。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-07-01 DOI: 10.1007/s00335-025-10148-6
Samuel J Widmayer, Lydia K Wooldridge, Emily Swanzey, Mary Barter, Chrystal Snow, Michael Saul, Qingchang Meng, Beth Dumont, Laura Reinholdt, Daniel M Gatti
{"title":"Low-coverage whole-genome sequencing facilitates accurate and cost-effective haplotype reconstruction in complex mouse crosses.","authors":"Samuel J Widmayer, Lydia K Wooldridge, Emily Swanzey, Mary Barter, Chrystal Snow, Michael Saul, Qingchang Meng, Beth Dumont, Laura Reinholdt, Daniel M Gatti","doi":"10.1007/s00335-025-10148-6","DOIUrl":"10.1007/s00335-025-10148-6","url":null,"abstract":"<p><p>The search for the underlying genetic contributions to complex traits and diseases relies on accurate genetic data from populations of interest. Outbred populations, like the Diversity Outbred (DO), are commonly genotyped using commercial SNP arrays, such as the Giga Mouse Universal Genotyping Array (GigaMUGA). However, array genotypes are expensive to collect, subject to significant ascertainment bias, and too sparse to capture the genetic structure of highly recombined mouse crosses. We investigated the efficacy of sequencing-based genotyping by comparing genotyping results between the GigaMUGA, double-digest restriction-site associated DNA sequencing (ddRADseq), and low-coverage whole-genome sequencing (lcWGS). We aligned reads at ~ 1× coverage and imputed segregating SNPs from the eight DO founder strains onto 48 DO genomes and reconstructed their haplotypes using R/qtl2. Haplotype reconstructions derived from all three methods were highly concordant. However, lcWGS more faithfully recapitulated crossover counts and identified more small (< 1 Mb) haplotype blocks at as low as 0.1× coverage. Over 90% of local expression quantitative trait loci identified in a set of 183 DO-derived embryoid bodies using the GigaMUGA were recalled by lcWGS at coverages as low as 0.1×. We recommend that lcWGS be adopted as the primary method of genotyping complex crosses, and cell-based resources derived from them because they are as accurate as array-based reconstructions, robust to ultra-low sequencing depths, may more accurately model haplotypes of the mouse genome that are difficult to resolve with dense reference data, and cost-effective.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators. 非小细胞肺癌图谱与分析:探索相互关联的致癌信号整合子。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-02-12 DOI: 10.1007/s00335-025-10110-6
Sai Bhavani Gottumukkala, Anbumathi Palanisamy
{"title":"Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.","authors":"Sai Bhavani Gottumukkala, Anbumathi Palanisamy","doi":"10.1007/s00335-025-10110-6","DOIUrl":"10.1007/s00335-025-10110-6","url":null,"abstract":"<p><p>Non-Small Cell lung cancer (NSCLC) is known for its fast progression, metastatic potency, and a leading cause of mortality globally. At diagnosis, approximately 30-40% of NSCLC patients already present with metastasis. Epithelial to mesenchymal transition (EMT) is a developmental program implicated in cancer progression and metastasis. Transforming Growth Factor-β (TGFβ) and its signalling plays a prominent role in orchestrating the process of EMT and cancer metastasis. In present study, a comprehensive molecular interaction map of TGFβ induced EMT in NSCLC was developed through an extensive literature survey. The map encompasses 394 species interconnected through 554 reactions, representing the relationship and complex interplay between TGFβ induced SMAD dependent and independent signalling pathways (PI3K/Akt, Wnt, EGFR, JAK/STAT, p38 MAPK, NOTCH, Hypoxia). The map, built using Cell Designer and compliant with SBGN and SBML standards, was subsequently translated into a logical modelling framework using CaSQ and dynamically analysed with Cell Collective. These analyses illustrated the complex regulatory dynamics, capturing the known experimental outcomes of TGFβ induced EMT in NSCLC including the co-existence of hybrid EM phenotype during transition. Hybrid EM phenotype is known to contribute for the phenotypic plasticity during metastasis. Network-based analysis identified the crucial network level properties and hub regulators, while the transcriptome-based analysis cross validated the prognostic significance and clinical relevance of key regulators. Overall, the map developed and the subsequent analyses offer deeper understanding of the complex regulatory network governing the process of EMT in NSCLC.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"573-600"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome engineering with Cas9 and AAV repair templates, successes and pitfalls. 基因组工程与Cas9和AAV修复模板,成功与缺陷。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-01-13 DOI: 10.1007/s00335-024-10099-4
M C Birling, Y Hérault, G Pavlovic
{"title":"Genome engineering with Cas9 and AAV repair templates, successes and pitfalls.","authors":"M C Birling, Y Hérault, G Pavlovic","doi":"10.1007/s00335-024-10099-4","DOIUrl":"10.1007/s00335-024-10099-4","url":null,"abstract":"<p><p>Genome editing, in particular the CRISPR/Cas9 system, is widely used to generate new animal models. However, the generation of mutations, such as conditional knock-out or knock-in, can remain complex and inefficient, in particular because of the difficulty to deliver the donor DNA (single or double stranded) into the nucleus of fertilized oocytes. The use of recombinant adeno-associated viruses (rAAV) as donor DNA is a rapidly developing approach that promises to improve the efficiency of creation of animal models. In this mini-review, we explore the progress and challenges of using CRISPR/Cas9 in combination with rAAV for precise genome editing. We will summarise the current knowledge of rAAV transduction, data on its use in rodent embryos in combination with CRISPR/Cas9 to easily generate sequence replacements or insertions, the limitations of rAAV and the unexpected events observed to date, and the protocol optimisations already in place to facilitate its use in the generation of animal models.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"376-383"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Complementarity and integration of animal and in vitro non-animal pre-clinical model systems- an Australian perspective. 动物和体外非动物临床前模型系统的互补性和整合-澳大利亚的观点。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-05-06 DOI: 10.1007/s00335-025-10132-0
Ruth M Arkell, Ernst J Wolvetang, Twishi Gulati, James E Hennessy, Adam P Hill, Thierry Jardé, Andrew J Kueh, Paul Q Thomas, Louise N Winteringham, Michael S Dobbie
{"title":"Complementarity and integration of animal and in vitro non-animal pre-clinical model systems- an Australian perspective.","authors":"Ruth M Arkell, Ernst J Wolvetang, Twishi Gulati, James E Hennessy, Adam P Hill, Thierry Jardé, Andrew J Kueh, Paul Q Thomas, Louise N Winteringham, Michael S Dobbie","doi":"10.1007/s00335-025-10132-0","DOIUrl":"10.1007/s00335-025-10132-0","url":null,"abstract":"<p><p>Recent advances in the development of pre-clinical models based on non-animal technologies (NATs) have stimulated expectations that the use of animals in research may soon be phased out. The true value of innovations in NATs and their applications lies, however, in enabling an expanded and integrated portfolio of complementary animal and non-animal model systems to improve the accuracy and efficiency of pre-clinical research and therapeutic development. The term NATs covers a range of techniques spanning in silico, cell free, organ-on-chip as well as in vitro techniques including three-dimensional cell culture models termed organoids. Of these, in vitro systems are currently the most broadly used in biomedicine laboratories and are the first NATs for which Australia has invested in nationwide support. The focus of this commentary is the importance of understanding the strengths and limitations of in vitro and animal models such that an integrated portfolio of complementary genetic models continues to evolve to best support pre-clinical research and therapeutic development pipelines.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"482-487"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the brain-joint axis: genetic, transcriptomic, and cohort insights from neuroticism to osteoarthritis. 解开脑-关节轴:从神经质到骨关节炎的遗传、转录组学和队列洞察。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-03-13 DOI: 10.1007/s00335-025-10112-4
Jingwei Zhang, Yingjie Li, Yongzhen Li, Hongwei Liu
{"title":"Unraveling the brain-joint axis: genetic, transcriptomic, and cohort insights from neuroticism to osteoarthritis.","authors":"Jingwei Zhang, Yingjie Li, Yongzhen Li, Hongwei Liu","doi":"10.1007/s00335-025-10112-4","DOIUrl":"10.1007/s00335-025-10112-4","url":null,"abstract":"<p><p>The causal relationships between neuroticism and osteoarthritis (OA) were inconclusive in observational studies. We conducted bidirectional two-sample Mendelian randomization (MR) and transcriptome-wide association studies to determine the associations and the underlying transcriptomic basis. The summary-level genome-wide association study data for any site OA, knee OA, erosive hand OA, and hip OA were mainly derived from UK Biobank, and neuroticism was derived from CTGlab. We then utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between neuroticism and OA in 11,948 participants of European ancestry from the National Health and Nutrition Examination Survey from 2005 to 2018. Bidirectional two-sample MR studies revealed that feelings of being fed-up, a sense of miserableness, mood swings, and a higher neuroticism score were all linked to an increased risk of OA. These factors were specifically associated with OA at various sites, including the knee. Conversely, there was no evidence to suggest that OA had any influence on traits related to neuroticism. In a comprehensive analysis that accounted for variables such as age, sex, blood lipids, blood glucose, body weight, smoking, alcohol consumption, and physical activity, it was determined that mental fluctuation significantly increased the incidence of self-reported OA (OR 1.37, 95% CI 1.20-1.58, P < 0.001) based on weighted regression. Further confirmation was provided by PSM analysis, which showed that mental fluctuation was associated with a higher incidence of self-reported OA (OR 1.28, 95% CI 1.08-1.52, P = 0.004). Moreover, differentially expressed genes were enriched in several biological processes, including the cell cycle, lipid metabolism, RNA processing, and immuno-inflammatory responses. The results revealed significant genetic and population-based associations, as well as underlying mechanisms, between neuroticism and osteoarthritis, supporting the concept of a brain-joint axis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"638-650"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of NETs-related genes as diagnostic biomarkers in ischemic stroke using RNA sequencing and single-cell analysis. 利用RNA测序和单细胞分析鉴定nets相关基因作为缺血性脑卒中的诊断生物标志物。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1007/s00335-025-10117-z
Rongxing Qin, Wei Xu, Qingchun Qin, Xiaojun Liang, Xinyu Lai, Minshan Xie, Li Chen
{"title":"Identification of NETs-related genes as diagnostic biomarkers in ischemic stroke using RNA sequencing and single-cell analysis.","authors":"Rongxing Qin, Wei Xu, Qingchun Qin, Xiaojun Liang, Xinyu Lai, Minshan Xie, Li Chen","doi":"10.1007/s00335-025-10117-z","DOIUrl":"10.1007/s00335-025-10117-z","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are increasingly recognized for their involvement in ischemic stroke (IS), yet their precise contribution to IS outcomes is not fully understood. This study aims to elucidate the role of NETs in IS progression and identify potential biomarkers and therapeutic targets. In this study, mice were subjected to middle cerebral artery occlusion (MCAO). RNA sequencing was conducted on brain tissue samples to identify differentially expressed genes (DEGs) using the \"limma\" package. The diagnostic potential of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Additionally, single-cell RNA sequencing data were analyzed with the Seurat package to further investigate the cellular dynamics. We identified DEGs, and NETs-related genes associated with IS progression. Specifically, Ceacam3, Tnf, Selp, and Fcgr4 were found to be upregulated in MCAO samples, exhibiting diagnostic value as biomarkers for IS. Immune infiltration analysis indicated associations between these genes and various immune cell types. Gene Set Enrichment Analysis (GSEA) revealed their involvement in IS-related pathways, including ferroptosis, IL-17 signaling, leukocyte transendothelial migration, necroptosis, and NETs formation. Single-cell data confirmed the expression of Tnf, Selp, and Fcgr4 in neutrophils. CellChat analysis uncovered key cell-cell interactions in IS, emphasizing the role of neutrophils in communicating with microglia and T cells via the JAM pathway, with Thbs1 and Cd47 as key mediators. The findings provide insights into the cellular and molecular mechanisms underlying IS and may pave the way for novel therapeutic strategies targeting NETs in IS patients.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"651-664"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and validation of mitochondrial endoplasmic reticulum membrane-related genes in atherosclerosis. 动脉粥样硬化中线粒体内质网膜相关基因的鉴定和验证。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-03-28 DOI: 10.1007/s00335-025-10124-0
Li-Rong Wang, Chun-Xi Zhang, Lv-Bo Tian, Jie Huang, Li-Jun Jia, Hao Tao, Neng-Wei Yu, Bing-Hu Li
{"title":"Identification and validation of mitochondrial endoplasmic reticulum membrane-related genes in atherosclerosis.","authors":"Li-Rong Wang, Chun-Xi Zhang, Lv-Bo Tian, Jie Huang, Li-Jun Jia, Hao Tao, Neng-Wei Yu, Bing-Hu Li","doi":"10.1007/s00335-025-10124-0","DOIUrl":"10.1007/s00335-025-10124-0","url":null,"abstract":"<p><p>The mitochondria-associated endoplasmic reticulum membrane is implicated in atherosclerosis (AS). However, its precise molecular mechanisms remain undefined. This study identified KLRC1 and SOCS2 as key protective genes against AS through transcriptomic analysis integrated with Mendelian randomization. Both genes exhibited significantly reduced expression in the AS group. Immune infiltration analysis revealed a strong positive correlation between activated CD8<sup>+</sup> T cells and these genes, while eosinophils displayed the most pronounced negative correlation with KLRC1, and regulatory T cells exhibited the strongest negative association with SOCS2. Notably, SOCS2 emerged as a pivotal protective factor, offering novel insights into AS pathogenesis and providing a robust theoretical foundation for early diagnosis and potential therapeutic strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"665-682"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the therapeutic effect of melatonin targeting common biomarkers in testicular germ cell tumor, prostate adenocarcinoma, and male infertility: an integrated biology approach. 探索褪黑素在睾丸生殖细胞瘤、前列腺腺癌和男性不育症中常见生物标志物的治疗效果:综合生物学方法。
IF 2.7 4区 生物学
Mammalian Genome Pub Date : 2025-06-01 Epub Date: 2025-03-08 DOI: 10.1007/s00335-025-10119-x
Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan
{"title":"Exploring the therapeutic effect of melatonin targeting common biomarkers in testicular germ cell tumor, prostate adenocarcinoma, and male infertility: an integrated biology approach.","authors":"Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan","doi":"10.1007/s00335-025-10119-x","DOIUrl":"10.1007/s00335-025-10119-x","url":null,"abstract":"<p><p>Globally, male infertility (MI) is a major concern. Several other comorbidities related to MI are testicular germ cell tumor (TGCT) and prostate adenocarcinoma (PRAD). This study focuses on finding the common biomarkers among these diseases and their interaction with Melatonin (MLT). The differential expressed genes were retrieved using the GEPIA2 database for TGCT and PRAD, whereas the DISGENET database for MI-related genes. InteractiVenn was performed in response to identify the common genes. The STAG3, RNF212, DDX3Y, DPY19L2, TPCN1, KLK3, GNRH1, DMD, CCDC146, and DNAH1 are found to be involved in all these diseases. The gene ontologies and pathway enrichment analysis were done for these significant genes in response to identifying and accessing the involvement of these genes in other processes. MLT is a neuroendocrine hormone with high therapeutic properties. MLT showed the best binding energy with DDX3Y among all the proteins. Molecular dynamic simulation (MDS) of MLT with DDX3Y was performed and found to be -52.382 ± 13.110 kJ/mol binding energy. The RMSD, RMSF, SASA, RG, H-bond, FEL, PCA, and MM-PBSA analysis confirm the stability and compactness of the DDX3Y-MLT complex. The MDS results indicate that MLT is a promising therapeutic option for enhancing DDX3Y expression, which will support spermatogenesis. Additionally, the hub genes were identified based on MCC parameters from the merged interactive network of common genes in response to finding significant genes that can be a potential biomarker for the diagnosis of diseases.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"614-629"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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