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基于生物信息学的研究:探究参与新型冠状病毒肺炎发病机制的促炎细胞因子TNFα和IL-6的结构与功能

Bioinformatic-based Study to Investigate the Structure and Function of Pro-inflammatory Cytokines TNFα and IL-6 Involved in the Pathogenesis of COVID-19.

作者信息

Norollahi Seyedeh Elham, Babaei Kosar, Balooei Vida, Karouei Seyed Masoud Hashemi, Ashoobi Mohammad Taghi, Asghari Gharakhyli Elahe, Samadani Ali Akbar

机构信息

Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.

Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.

出版信息

Iran J Pathol. 2024 Spring;19(2):205-217. doi: 10.30699/IJP.2024.2015557.3211. Epub 2024 Feb 15.

Abstract

BACKGROUND & OBJECTIVE: Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection.

METHODS

To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed.

RESULTS

The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways.

CONCLUSION

IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.

摘要

背景与目的

除了对新冠病毒进行临床和实验室研究外,新冠病毒免疫遗传学领域的生物信息学研究尤为重要。在这方面,研究表明,新冠病毒患者体内肿瘤坏死因子α(TNFα)和白细胞介素-6(IL-6)水平较高,在新冠重症病例中,IL-6、TNF-α及其他细胞因子的产生会大幅增加。另一方面,研究IL-6和TNFα的分子结构与受体以及受体蛋白的结构分析,可能有助于制定针对新冠病毒感染的新治疗方案。

方法

为了在包含来自基因表达综合数据库(GEO)转录谱的微阵列数据集中识别新冠病毒患者中具有显著差异表达的基因,下载了编程语言R版本4.2.1中的GEO查询包版本2.64.2。通过这种方式,还对差异表达基因(DEGs)、维基通路(WikiPathways)、REGO、基因本体和STRING数据库进行了功能富集分析并加以应用。

结果

对参与新冠病毒发病机制的促炎细胞因子TNFα和IL-6的结构与功能进行了研究,总体而言,在本研究中进行各种分析并从京都基因与基因组百科全书(KEGG)数据库中提取一系列差异表达基因后,最终的5个差异表达基因包括CXCL14、CXCL6、CCL8、CXCR1、TNFRSF10,并观察到它们在不同通路中的关系和表达效应。

结论

IL-6和TNFα参与了与细胞因子(包括IL-6和TNF-α)激活以及细胞因子风暴有直接和间接关系的免疫过程,这表明它们在新冠病毒患者出现包括急性呼吸窘迫综合征(ARDS)在内的问题和并发症形成过程中发挥了作用。当然,确定这些基因各自的有效性还需要更专业的临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022a/11304465/ed1841d26e7b/ijp-19-205-g001.jpg

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