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伴或不伴海马硬化的颞叶癫痫患者免疫途径的改变

Altered immune pathways in patients of temporal lobe epilepsy with and without hippocampal sclerosis.

作者信息

Che Xiang-Qian, Zhan Shi-Kun, Song Jiao-Jiao, Deng Yu-Lei, Sun Zhan-Fang, Che Zai-Qian, Liu Jun

机构信息

Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Neurosurgery, Centre for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Sci Rep. 2024 Jun 13;14(1):13661. doi: 10.1038/s41598-024-63541-7.

Abstract

Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

摘要

在过去几十年中,免疫反应一直被怀疑参与癫痫的发病机制。为了评估颞叶癫痫(TLE)中与免疫相关的途径,我们探索了有和没有海马硬化(HS)的TLE患者中改变的免疫途径。我们分析了3例TLE-HS患者和3例TLE-非HS患者的RNA测序数据,包括差异表达RNA的鉴定、功能途径富集、蛋白质-蛋白质相互作用网络以及ceRNA调控网络的构建。我们阐述了人类TLE-HS中与免疫相关的分子和途径图谱。此外,我们在TLE-HS患者中鉴定出了几个与免疫相关的差异基因,如HSP90AA1和SOD1。进一步的ceRNA调控网络分析发现,在TLE-HS患者中,SOX2-OT与miR-671-5p相关联并上调了靶基因SPP1。此外,我们发现在包括TLE-HS患者和动物模型在内的五个不同数据库中,SOX2-OT和SPP1均显著上调。我们的研究结果确定了TLE-HS患者和动物模型中首个与免疫相关的基因和可能的调控途径,这为患者和动物模型的疾病发病机制提供了新的见解。免疫相关的SOX2-OT/miR-671-5p/SPP1轴可能是TLE-HS的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d308/11176392/b052af573289/41598_2024_63541_Fig1_HTML.jpg

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