Ding Peng-Li, Zhang Kai-Xin, Yao Fang, Cui Wen-Qiang, Liu Zhen-Ling, Wang Yi-Ran, Wang Xiang-Ying, Liu Wei, Zhao Heng-Ye, Wu Hong-Yun, Wang Ya-Han, Xu Xiang-Qing
First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Nursing Department, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong, China.
Mediators Inflamm. 2025 Jun 6;2025:6808184. doi: 10.1155/mi/6808184. eCollection 2025.
The pathophysiological progression during the hyperacute phase of acute ischemic stroke (AIS) critically determines clinical outcomes. Identification of phase-specific biomarkers and elucidation of their temporal regulatory mechanisms are pivotal for optimizing therapeutic interventions. Disease signature genes and their mechanisms of action were screened based on the Gene Expression Omnibus database. This involved the use of differentially expressed gene screening, weighted gene co-expression network analysis, Mfuzz analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, support vector machines, random forest algorithms, and gene set enrichment analysis. The expression of disease-characteristic genes and their related mechanisms were further validated in both in vivo and in vitro models. Six hyperacute-phase signature genes (, , , , , and ) were identified in the hyperacute phase of AIS. In light of the gene effect mechanism, the regulation of the neuroinflammatory response and apoptosis by the TLR2/TLR4/NF-B pathway was monitored in the hyperacute phase of AIS at three times: 3, 6, and 12 h. The results indicated a progressively intensified neuroinflammatory response and the fluctuating growth of early apoptosis changes. This study systematically identifies hyperacute-phase-specific biomarkers in AIS and delineates their temporal regulatory logic. The time-course dynamics of neuronal apoptosis and inflammatory regulation in the hyperacute phase of AIS were monitored. The observed biphasic apoptotic pattern provides mechanistic insights for developing chronologically targeted therapies, such as timed inhibition of TLR4/CD86 during 0-3 h to block inflammatory initiation, or administration of Agpat1 agonists at 3-6 h to stabilize mitochondrial function. These findings help alleviate the current 'molecular blind spot' in early stroke diagnosis and intervention.
急性缺血性卒中（AIS）超急性期的病理生理进展严重决定临床结局。识别阶段特异性生物标志物并阐明其时间调控机制对于优化治疗干预至关重要。基于基因表达综合数据库筛选疾病特征基因及其作用机制。这涉及使用差异表达基因筛选、加权基因共表达网络分析、Mfuzz分析、基因本体论、京都基因与基因组百科全书富集分析、支持向量机、随机森林算法和基因集富集分析。在体内和体外模型中进一步验证疾病特征基因的表达及其相关机制。在AIS超急性期鉴定出六个超急性期特征基因（、、、、、和）。根据基因效应机制，在AIS超急性期三个时间点（3、6和12小时）监测TLR2/TLR4/NF-κB通路对神经炎症反应和细胞凋亡的调节。结果表明神经炎症反应逐渐增强，早期细胞凋亡变化呈波动增长。本研究系统地鉴定了AIS超急性期特异性生物标志物，并描绘了它们的时间调控逻辑。监测了AIS超急性期神经元凋亡和炎症调节的时间进程动态。观察到的双相凋亡模式为开发按时间顺序靶向治疗提供了机制见解，例如在0-3小时期间定时抑制TLR4/CD86以阻断炎症起始，或在3-6小时给予Agpat1激动剂以稳定线粒体功能。这些发现有助于缓解当前早期卒中诊断和干预中的“分子盲点”。
