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Vogt-Koyanagi-Harada 病相关关键通路和药物靶点的综合分析。

Integrated Analysis of Key Pathways and Drug Targets Associated With Vogt-Koyanagi-Harada Disease.

机构信息

The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, China.

出版信息

Front Immunol. 2020 Dec 15;11:587443. doi: 10.3389/fimmu.2020.587443. eCollection 2020.

Abstract

BACKGROUND

Vogt-Koyanagi-Harada (VKH) disease is a complex disease associated with multiple molecular immunological mechanisms. As the underlying mechanism for VKH disease is unclear, we hope to utilize an integrated analysis of key pathways and drug targets to develop novel therapeutic strategies.

METHODS

Candidate genes and proteins involved in VKH disease were identified through text-mining in the PubMed database. The GO and KEGG pathway analyses were used to examine the biological functions of the involved pathways associated with this disease. Molecule-related drugs were predicted through Drug-Gene Interaction Database (DGIdb) analysis.

RESULTS

A total of 48 genes and 54 proteins were associated with VKH disease. Forty-two significantly altered pathways were identified through pathway analysis and were mainly related to immune and inflammatory responses. The top five of significantly altered pathways were termed as "inflammatory bowel disease," "cytokine-cytokine receptor interaction," "allograft rejection," "antigen processing," and "presentation and Herpes simplex infection" in the KEGG database. IFN-γ and IL-6 were identified as the key genes through network analysis. The DGIdb analysis predicted 48 medicines as possible drugs for VKH disease, among which Interferon Alfa-2B was co-associated both with IFN-γ and IL-6.

CONCLUSIONS

In this study, systematic analyses were utilized to detect key pathways and drug targets in VKH disease bioinformatics analysis. IFN-γ and IL-6 were identified as the key mediators and possible drug targets in VKH disease. Interferon Alfa-2B was predicted to be a potentially effective drug for VKH disease treatment by targeting IFN-γ and IL-6, which warrants further experimental and clinical investigations.

摘要

背景

Vogt-小柳-原田(VKH)病是一种与多种分子免疫机制相关的复杂疾病。由于 VKH 病的潜在机制尚不清楚,我们希望利用关键途径和药物靶点的综合分析来开发新的治疗策略。

方法

通过在 PubMed 数据库中进行文本挖掘,确定与 VKH 病相关的候选基因和蛋白质。GO 和 KEGG 途径分析用于研究与该疾病相关的途径的生物学功能。通过药物-基因相互作用数据库(DGIdb)分析预测与分子相关的药物。

结果

共确定了 48 个基因和 54 个蛋白质与 VKH 病相关。通过途径分析确定了 42 个显著改变的途径,这些途径主要与免疫和炎症反应有关。KEGG 数据库中排名前五的显著改变途径分别为“炎症性肠病”、“细胞因子-细胞因子受体相互作用”、“同种异体移植排斥”、“抗原加工和呈递”和“单纯疱疹感染”。通过网络分析确定 IFN-γ 和 IL-6 为关键基因。DGIdb 分析预测了 48 种药物作为 VKH 病的潜在药物,其中干扰素 Alfa-2B 与 IFN-γ 和 IL-6 均有共同关联。

结论

本研究通过系统分析,利用生物信息学分析检测 VKH 病的关键途径和药物靶点。IFN-γ 和 IL-6 被确定为 VKH 病的关键介质和可能的药物靶点。干扰素 Alfa-2B 通过靶向 IFN-γ 和 IL-6 被预测为 VKH 病治疗的潜在有效药物,值得进一步的实验和临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a5/7769821/43b1d8ca2073/fimmu-11-587443-g001.jpg

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