Bioinformatics screening and verification of ischemic stroke-related key genes and drug prediction.

IF 1.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY General physiology and biophysics Pub Date : 2024-09-01 DOI:10.4149/gpb_2024023
Shuai Jiang, Zhanhui Liu, Xian Zhang, Rui Zhang, Bo Sun, Chao Gao, Pengfei Hou, Meirong Sun
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Abstract

Stroke is one of the major causes of disability and death worldwide. The lack of effective medical treatment for stroke heightens the need for new therapeutic targets. In this study, we obtained two microarray data sets from the Gene Expression Omnibus (GEO) database and identified differential genes (DEGs) between MCAO and control groups. Then, enrichment analysis of the DEGs was performed using DAVID and Metascape. The results show 27 DEGs shared between the two datasets. The functional enrichment analysis showed that these genes are mainly enriched in immune response, complement and coagulation cascades, apoptotic processes. The four hub genes (C1qc, Fcgr2b, C1qb, and Cd14) were screened out using the Cytoscape. Next, real-time PCR and Western blot analysis showed that expression of C1q and CD14 increased at 14 days after tMCAO. Furthermore, we took eight small molecule compounds with the lowest score using Cmap and studied their background characteristics. These results are built on a meta-analysis of data, which are generally accessible from the online space. Finally, we evaluated the protective effect of the rolipram through behavior tests after tMCAO, and results showed that the rolipram significantly attenuated neurobehavioral dysfunction at 14 days after brain ischemia. The present results provide novel insights into the biological process and potential therapeutic drugs involved in stroke.

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缺血性中风相关关键基因的生物信息学筛选和验证及药物预测。
中风是全球致残和致死的主要原因之一。脑卒中缺乏有效的医疗手段,因此更需要新的治疗靶点。本研究从基因表达总库(Gene Expression Omnibus,GEO)数据库中获得了两组微阵列数据,并确定了 MCAO 组和对照组之间的差异基因(DEGs)。然后,使用 DAVID 和 Metascape 对 DEGs 进行了富集分析。结果显示,两个数据集共有 27 个 DEGs。功能富集分析表明,这些基因主要富集在免疫反应、补体和凝血级联、细胞凋亡过程中。利用 Cytoscape 筛选出了四个中心基因(C1qc、Fcgr2b、C1qb 和 Cd14)。接下来,实时 PCR 和 Western 印迹分析表明,C1q 和 CD14 的表达在 tMCAO 后 14 天有所增加。此外,我们还提取了使用 Cmap 得分最低的八个小分子化合物,并研究了它们的背景特征。这些结果建立在荟萃分析数据的基础上,这些数据一般可从网络空间获取。最后,我们通过tMCAO后的行为测试评估了罗利普兰的保护作用,结果显示罗利普兰能显著减轻脑缺血后14天的神经行为功能障碍。本研究结果为了解中风的生物学过程和潜在治疗药物提供了新的视角。
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来源期刊
General physiology and biophysics
General physiology and biophysics 生物-生化与分子生物学
CiteScore
2.70
自引率
0.00%
发文量
42
审稿时长
6-12 weeks
期刊介绍: General Physiology and Biophysics is devoted to the publication of original research papers concerned with general physiology, biophysics and biochemistry at the cellular and molecular level and is published quarterly by the Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences.
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