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使用整合生物信息学分析鉴定与心肌梗死后心力衰竭相关的时间序列差异表达基因和途径。

Identification of time‑series differentially expressed genes and pathways associated with heart failure post‑myocardial infarction using integrated bioinformatics analysis.

机构信息

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

出版信息

Mol Med Rep. 2019 Jun;19(6):5281-5290. doi: 10.3892/mmr.2019.10190. Epub 2019 Apr 24.

Abstract

Heart failure (HF) secondary to acute myocardial infarction (AMI) is a public health concern. The current study aimed to investigate differentially expressed genes (DEGs) and their possible function in HF post‑myocardial infarction. The GSE59867 dataset included microarray data from peripheral blood samples obtained from HF and non‑HF patients following AMI at 4 time points (admission, discharge, and 1 and 6 months post‑AMI). Time‑series DEGs were analyzed using R Bioconductor. Functional enrichment analysis was performed, followed by analysis of protein‑protein interactions (PPIs). A total of 108 DEGs on admission, 32 DEGs on discharge, 41 DEGs at 1 month post‑AMI and 19 DEGs at 6 months post‑AMI were identified. Among these DEGs, 4 genes were downregulated at all the 4 time points. These included fatty acid desaturase 2, leucine rich repeat neuronal protein 3, G‑protein coupled receptor 15 and adenylate kinase 5. Functional enrichment analysis revealed that these DEGs were mainly enriched in 'inflammatory response', 'immune response', 'toll‑like receptor signaling pathway' and 'NF‑κβ signaling pathway'. Furthermore, PPI network analysis revealed that C‑X‑C motif chemokine ligand 8 and interleukin 1β were hub genes. The current study identified candidate DEGs and pathways that may serve important roles in the development of HF following AMI. The results obtained in the current study may guide the development of novel therapeutic agents for HF following AMI.

摘要

心肌梗死后心力衰竭(HF)是一个公共卫生关注点。本研究旨在探讨心肌梗死后 HF 中差异表达基因(DEGs)及其可能的功能。GSE59867 数据集包含了心肌梗死后 4 个时间点(入院时、出院时以及心肌梗死后 1 个月和 6 个月)从 HF 和非 HF 患者外周血样本中获得的微阵列数据。使用 R Bioconductor 分析时间序列 DEGs。进行功能富集分析,然后分析蛋白质-蛋白质相互作用(PPIs)。入院时有 108 个 DEGs,出院时有 32 个 DEGs,心肌梗死后 1 个月时有 41 个 DEGs,心肌梗死后 6 个月时有 19 个 DEGs。在这些 DEGs 中,有 4 个基因在所有 4 个时间点都下调。这些基因包括脂肪酸去饱和酶 2、富含亮氨酸的重复神经元蛋白 3、G 蛋白偶联受体 15 和腺苷酸激酶 5。功能富集分析显示,这些 DEGs 主要富集在“炎症反应”、“免疫反应”、“Toll 样受体信号通路”和“NF-κB 信号通路”。此外,PPI 网络分析显示,C-X-C 基序趋化因子配体 8 和白细胞介素 1β 是枢纽基因。本研究确定了候选 DEGs 和通路,它们可能在 AMI 后 HF 的发展中发挥重要作用。本研究的结果可能为 AMI 后 HF 的新型治疗药物的开发提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a97/6522961/c0e504849fbc/MMR-19-06-5281-g00.jpg

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