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运用综合生物信息学分析鉴定可卡因成瘾的关键基因和治疗药物

Identification of key genes and therapeutic drugs for cocaine addiction using integrated bioinformatics analysis.

作者信息

Wang Xu, Sun Shibin, Chen Hongwei, Yun Bei, Zhang Zihan, Wang Xiaoxi, Wu Yifan, Lv Junjie, He Yuehan, Li Wan, Chen Lina

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Front Neurosci. 2023 Jul 4;17:1201897. doi: 10.3389/fnins.2023.1201897. eCollection 2023.

Abstract

INTRODUCTION

Cocaine is a highly addictive drug that is abused due to its excitatory effect on the central nervous system. It is critical to reveal the mechanisms of cocaine addiction and identify key genes that play an important role in addiction.

METHODS

In this study, we proposed a centrality algorithm integration strategy to identify key genes in a protein-protein interaction (PPI) network constructed by deferential genes from cocaine addiction-related datasets. In order to investigate potential therapeutic drugs for cocaine addiction, a network of targeted relationships between nervous system drugs and key genes was established.

RESULTS

Four key genes (JUN, FOS, EGR1, and IL6) were identified and well validated using CTD database correlation analysis, text mining, independent dataset analysis, and enrichment analysis methods, and they might serve as biomarkers of cocaine addiction. A total of seventeen drugs have been identified from the network of targeted relationships between nervous system drugs and key genes, of which five (disulfiram, cannabidiol, dextroamphetamine, diazepam, and melatonin) have been shown in the literature to play a role in the treatment of cocaine addiction.

DISCUSSION

This study identified key genes and potential therapeutic drugs for cocaine addiction, which provided new ideas for the research of the mechanism of cocaine addiction.

摘要

引言

可卡因是一种极易成瘾的药物,因其对中枢神经系统的兴奋作用而被滥用。揭示可卡因成瘾的机制并确定在成瘾中起重要作用的关键基因至关重要。

方法

在本研究中,我们提出了一种中心性算法整合策略,以在由可卡因成瘾相关数据集中的差异基因构建的蛋白质-蛋白质相互作用(PPI)网络中识别关键基因。为了研究可卡因成瘾的潜在治疗药物,建立了神经系统药物与关键基因之间的靶向关系网络。

结果

通过CTD数据库相关性分析、文本挖掘、独立数据集分析和富集分析方法,鉴定并充分验证了四个关键基因(JUN、FOS、EGR1和IL6),它们可能作为可卡因成瘾的生物标志物。从神经系统药物与关键基因之间的靶向关系网络中总共鉴定出17种药物,其中五种(双硫仑、大麻二酚、右旋苯丙胺、地西泮和褪黑素)在文献中已显示在可卡因成瘾治疗中发挥作用。

讨论

本研究确定了可卡因成瘾的关键基因和潜在治疗药物,为可卡因成瘾机制的研究提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ca5/10352680/bfd6023867c2/fnins-17-1201897-g0001.jpg

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