多组学和实验验证确定GPX7和谷胱甘肽相关氧化应激是缺血性卒中的潜在生物标志物。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tianzhi Li, Sijie Zhang, Jinshan He, Hongyan Li, Jingsong Kang
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引用次数: 0

摘要

缺血性中风(IS)是全世界致残和死亡的主要原因,其高发病率、致残率和复发率给家庭和社会带来了沉重的经济负担。近年来的研究表明,氧化应激在缺血性脑卒中的病理生理机制中起着关键作用,不仅参与急性期神经元损伤的发生和发展,而且通过表观遗传修饰等分子机制显著影响缺血性脑卒中的远期预后。然而,氧化应激相关基因在IS中的潜在靶点及其作用机制仍有待阐明。本研究旨在系统分析IS中氧化应激相关基因的功能及意义。我们从GEO数据库中获取了is相关基因表达数据集,并整合了Genecards数据库中已知的氧化应激相关基因进行交叉分析。利用无监督共识聚类和一系列机器学习算法进行多维特征筛选,最终确定了特征基因GPX7。使用MCPcounter评估了该基因与免疫细胞浸润之间的相关性,并确定了一种潜在的治疗剂——谷胱甘肽。通过分子对接(MD)分析证实了两者的结合。此外,对单细胞RNA测序数据进行分析,进一步揭示其在不同细胞类型中的表达及其生物学意义。最后,我们利用Wistar大鼠大脑中动脉闭塞(MCAO)模型进行了体内实验,结果表明GPX7在IS中发挥了关键作用,为IS的精准治疗提供了新的理论依据和潜在的干预靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multi-Omics and Experimental Validation Identify GPX7 and Glutathione-Associated Oxidative Stress as Potential Biomarkers in Ischemic Stroke.

Ischemic stroke (IS) is the leading cause of disability and death worldwide, and its high incidence, disability and recurrence rates impose a heavy economic burden on families and society. Recent studies have shown that oxidative stress plays a key role in the pathophysiological mechanisms of ischemic stroke, not only participating in the onset and development of neuronal damage in the acute phase but also significantly influencing the long-term prognosis of ischemic stroke through molecular mechanisms, such as epigenetic modifications. However, the potential targets of oxidative stress-related genes in IS and their mechanisms of action remain to be elucidated. The aim of this study was to systematically analyse the function and significance of oxidative stress-related genes in IS. We obtained IS-related gene expression datasets from the GEO database and integrated known oxidative stress-related genes from the Genecards database for cross-analysis. Multidimensional feature screening using unsupervised consensus clustering and a series of machine learning algorithms led to the identification of the signature gene GPX7. The correlation between this gene and immune cell infiltration was assessed using MCPcounter and a potential therapeutic agent, glutathione, was identified. Binding was verified by molecular docking (MD) analysis. In addition, single-cell RNA sequencing data were analysed to further reveal expression in different cell types and its biological significance. Finally, we performed in vivo experiments using the Wistar rat middle cerebral artery occlusion (MCAO) model, and the results indicated that GPX7 plays a key role in IS, providing a new theoretical basis and potential intervention target for the precise treatment of IS.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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