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利用基于微阵列的转录组分析和单细胞测序,识别并分析癫痫中与铁死亡相关的分子模块和免疫特征。

Identify and analyze ferroptosis-related molecular modules and immune signatures in epilepsy using microarray-based transcriptome profiling and single-cell sequencing.

作者信息

Huang Cong, Wei Fan, You Zhipeng, Li Jiran, Liu Yang, Liu Xingan, Fan Zhijie, He Yunmin, Gao Xiaoying, Sun Jiahang

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150081, PR China.

Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150000, PR China.

出版信息

Gene. 2025 Mar 20;942:149227. doi: 10.1016/j.gene.2025.149227. Epub 2025 Jan 21.

Abstract

Currently, the pathogenesis of epilepsy remains poorly understood. Although there is evidence indicating that iron death might play a significant role, its molecular immunological mechanisms are largely unknown. This study was designed to analyze and explore the molecular mechanisms and immunological characteristics of iron death-related genes in epilepsy. We obtained datasets of blood and brain tissues for epilepsy from the GEO database and the set of iron death-related genes from FerrDb. Through two machine learning algorithms, we identified three Hub genes, namely RELA, TFRC, and QSOX1. Unsupervised clustering revealed two distinct clusters. Immune infiltration analysis demonstrated that one cluster had significantly higher immune infiltration. We established an epilepsy diagnostic model and nomogram. The results were confirmed by RT-qPCR and Western Blot. Single-cell analysis showed that the SPP1 signalling pathway was overly activated in astrocytes and microglia. This study offers new perspectives and a theoretical foundation for the diagnosis of epilepsy.

摘要

目前,癫痫的发病机制仍知之甚少。尽管有证据表明铁死亡可能起重要作用,但其分子免疫机制 largely unknown。本研究旨在分析和探索癫痫中铁死亡相关基因的分子机制和免疫特征。我们从GEO数据库获得癫痫的血液和脑组织数据集,并从FerrDb获得铁死亡相关基因集。通过两种机器学习算法,我们鉴定出三个枢纽基因,即RELA、TFRC和QSOX1。无监督聚类显示出两个不同的簇。免疫浸润分析表明,其中一个簇具有明显更高的免疫浸润。我们建立了癫痫诊断模型和列线图。结果通过RT-qPCR和Western Blot得到证实。单细胞分析表明,SPP1信号通路在星形胶质细胞和小胶质细胞中过度激活。本研究为癫痫的诊断提供了新的视角和理论基础。

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