Disulfidptosis and its Role in Peripheral Blood Immune Cells after a Stroke: A New Frontier in Stroke Pathogenesis.

Current neurovascular research Pub Date : 2024-01-01 DOI:10.2174/0115672026286243240105115419

Shan-Peng Liu, Cuiying Liu, Baohui Xu, Hongmei Zhou, Heng Zhao

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Abstract

Background: Stroke-Induced Immunodepression (SIID) is characterized by apoptosis in blood immune populations, such as T cells, B cells, NK cells, and monocytes, leading to the clinical presentation of lymphopenia. Disulfidptosis is a novel form of programmed cell death characterized by accumulating disulfide bonds in the cytoplasm, resulting in cellular dysfunction and eventual cell death.

Objective: In this study, we investigated the association between disulfidptosis and stroke by analyzing gene sequencing data from peripheral blood samples of stroke patients.

Methods: Differential gene expression analysis identified a set of disulfidptosis-related genes (DRGs) significantly associated with stroke. Initial exploration identified 32 DRGs and their interactions. Our study encompassed several analyses to understand the molecular mechanisms of DRGs in stroke. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered modules of co-expressed genes in stroke samples, and differentially expressed gene (DEG) analysis highlighted 1643 key genes.

Results: These analyses converged on four hub genes of DRGs (SLC2A3, SLC2A14, SLC7A11, NCKAP1) associated with stroke. Immune cell composition analysis indicated positive correlations between hub genes and macrophages M1, M2, and neutrophils and negative associations with CD4+ and CD8+ T cells, B cells, and NK cells. Sub-cluster analysis revealed two distinct clusters with different immune cell expression profiles. Gene Set Enrichment Analysis (GSEA) demonstrated enrichment of apoptosis-related pathways, neurotrophin signaling, and actin cytoskeleton regulation. Associations between hub genes and apoptosis, necroptosis, ferroptosis, and cuproptosis, were also identified.

Conclusion: These results suggest that the DRG hub genes are interconnected with various cell death pathways and immune processes, potentially contributing to stroke pathological development.

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中风后外周血免疫细胞的二硫化及其作用：中风发病机制的新前沿。

背景：脑卒中诱导的免疫抑制（SIID）的特点是血液中的免疫细胞群（如T细胞、B细胞、NK细胞和单核细胞）凋亡，导致临床表现为淋巴细胞减少。二硫化硫是一种新型的程序性细胞死亡，其特点是二硫键在细胞质中累积，导致细胞功能紊乱并最终死亡：在这项研究中，我们通过分析中风患者外周血样本的基因测序数据，研究了二硫化血症与中风之间的关联：差异基因表达分析确定了一组与中风显著相关的二硫化相关基因（DRGs）。初步研究发现了 32 个 DRGs 及其相互作用。我们的研究包括多项分析，以了解 DRGs 在中风中的分子机制。加权基因共表达网络分析（WGCNA）发现了中风样本中的共表达基因模块，差异表达基因（DEG）分析突出了1643个关键基因：结果：这些分析发现了与中风相关的四个 DRGs 中枢基因（SLC2A3、SLC2A14、SLC7A11 和 NCKAP1）。免疫细胞组成分析表明，中心基因与巨噬细胞 M1、M2 和中性粒细胞呈正相关，而与 CD4+ 和 CD8+ T 细胞、B 细胞和 NK 细胞呈负相关。子簇分析表明，两个不同的簇具有不同的免疫细胞表达谱。基因组富集分析（Gene Set Enrichment Analysis，GSEA）显示了凋亡相关通路、神经营养素信号转导和肌动蛋白细胞骨架调节的富集。此外，还发现了中枢基因与细胞凋亡、坏死、铁凋亡和杯状凋亡之间的关联：这些结果表明，DRG 中枢基因与各种细胞死亡途径和免疫过程相互关联，可能导致中风病理发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Current neurovascular research

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