School of Public Health, Jilin University, Changchun, 130021, Jilin, China.
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China.
Eur J Med Res. 2023 Oct 5;28(1):400. doi: 10.1186/s40001-023-01291-4.
Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS.
By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS.
In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein-Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations.
The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood-brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score.
Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.
人类水痘带状疱疹病毒（VZV）的感染率为 95%，VZV 感染与缺血性脑卒中（IS）密切相关。然而，VZV 引起的 IS 的潜在分子机制尚不清楚，也没有有效的药物来治疗和预防 VZV 引起的 IS。
本研究通过整合生物信息学，探讨 VZV 与 IS 之间的相互作用以及治疗和预防 VZV 引起的 IS 的潜在药物。
本研究使用 GEO 数据库中的 VZV 和 IS 数据集来确定共同基因。然后，进行了包括基因本体论、京都基因与基因组百科全书和蛋白质-蛋白质相互作用网络分析在内的生物信息学分析。进一步获得了核心基因、转录因子（TF）基因相互作用、TF-miRNA 共调控网络和潜在药物。最后，通过分子对接和分子动力学模拟进行验证。
使用多种生物信息学工具研究了 VZV 引起的 IS 的潜在分子机制。十个核心基因包括 COL1A2、DCN、PDGFRB、ACTA2 等。TF 基因和 miRNAs 包括 JUN、FOS、CREB、BRCA1、PPARG、STAT3、miR-29 等。可能涉及一系列机制，如炎症、氧化应激、血脑屏障破坏、泡沫细胞生成等。最后，我们提出白藜芦醇作为预防和治疗 VZV 引起的 IS 的潜在治疗药物。分子对接和分子动力学结果表明，白藜芦醇与核心基因表现出较强的结合评分。
白藜芦醇可能是预防和治疗 VZV-IS 的一种替代药物。未来需要更多的体内和体外研究来充分探索 VZV 与 IS 之间的分子机制和药物开发。
