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通过生物信息学和实验研究探索氧化应激相关基因在 LPS 诱导的急性肺损伤中的作用。

Exploration of the role of oxidative stress-related genes in LPS-induced acute lung injury via bioinformatics and experimental studies.

机构信息

Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, People's Republic of China.

Department of Respiratory Medicine, Key Cite of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

出版信息

Sci Rep. 2023 Dec 9;13(1):21804. doi: 10.1038/s41598-023-49165-3.

Abstract

During the progression of acute lung injury (ALI), oxidative stress and inflammatory responses always promote each other. The datasets analyzed in this research were acquired from the Gene Expression Omnibus (GEO) database. The Weighted Gene Co-expression Network Analysis (WGCNA) and limma package were used to obtain the ALI-related genes (ALIRGs) and differentially expressed genes (DEGs), respectively. In total, two biological markers (Gch1 and Tnfaip3) related to oxidative stress were identified by machine learning algorithms, Receiver Operator Characteristic (ROC), and differential expression analyses. The area under the curve (AUC) value of biological markers was greater than 0.9, indicating an excellent power to distinguish between ALI and control groups. Moreover, 15 differential immune cells were selected between the ALI and control samples, and they were correlated to biological markers. The transcription factor (TF)-microRNA (miRNA)-Target network was constructed to explore the potential regulatory mechanisms. Finally, based on the quantitative reverse transcription polymerase chain reaction (qRT-PCR), the expression of Gch1 and Tnfaip3 was significantly higher in ALI lung tissue than in healthy controls. In conclusion, the differences in expression profiles between ALI and normal controls were found, and two biological markers were identified, providing a research basis for further understanding the pathogenesis of ALI.

摘要

在急性肺损伤 (ALI) 的进展过程中,氧化应激和炎症反应总是相互促进。本研究分析的数据来自基因表达综合数据库 (GEO)。使用加权基因共表达网络分析 (WGCNA) 和 limma 包分别获得与 ALI 相关的基因 (ALIRGs) 和差异表达基因 (DEGs)。通过机器学习算法、接收器操作特性 (ROC) 和差异表达分析,共鉴定出 2 个与氧化应激相关的生物标志物 (Gch1 和 Tnfaip3)。生物标志物的曲线下面积 (AUC) 值大于 0.9,表明其区分 ALI 和对照组的能力非常出色。此外,在 ALI 和对照组样本之间选择了 15 个差异免疫细胞,并与生物标志物相关联。构建转录因子 (TF)-microRNA (miRNA)-靶标网络,以探讨潜在的调控机制。最后,基于定量逆转录聚合酶链反应 (qRT-PCR),ALI 肺组织中 Gch1 和 Tnfaip3 的表达明显高于健康对照组。总之,发现了 ALI 与正常对照组之间表达谱的差异,并鉴定出两个生物标志物,为进一步了解 ALI 的发病机制提供了研究基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e23c/10710410/c1e08b41e7e5/41598_2023_49165_Fig1_HTML.jpg

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