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缺血性脑卒中中细胞衰老和昼夜节律的治疗靶点。

Treatment targets of cellular senescence and circadian rhythms in ischemic stroke.

作者信息

Zeng Fukang, Wang Mengjuan, He Menghao, Li Zhong, Zhang Yuxing

机构信息

Department of Critical Care Medicine, The Hospital of Xiangxi Tujia and Miao Autonomous Prefecture Ethnic Chinese Medicine, Jishou City, Hunan Province, China.

Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Yuhua District, Changsha City, Hunan Province, People's Republic of China.

出版信息

Medicine (Baltimore). 2025 Jul 4;104(27):e43220. doi: 10.1097/MD.0000000000043220.

Abstract

Ischemic stroke poses a substantial public health burden due to its high incidence, rendering it an urgent medical concern. Emerging evidence suggests that cellular senescence and circadian rhythms are closely linked to the onset of cerebral infarction and may represent promising therapeutic targets. Accordingly, we retrieved datasets GSE16561 and GSE22255 from the Gene Expression Omnibus and extracted cellular senescence- and circadian rhythm-related genes from the GeneCards database. Through bioinformatics analysis, we identified key targets associated with cellular senescence and circadian rhythm in cerebral infarction, specifically CREBBP, FOS, CDK4, MMP9, PTEN, and HIF1A. Complementing these findings with in vitro experiments, our results demonstrate that the expression of these genes and proteins at these core targets are elevated to varying degrees in an in vitro model of cerebral infarction. These findings provide compelling evidence supporting the pivotal role of cellular senescence- and circadian rhythm-related genes in the pathogenesis of ischemic stroke.

摘要

缺血性中风因其高发病率而给公共卫生带来沉重负担,使其成为一个紧迫的医学问题。新出现的证据表明,细胞衰老和昼夜节律与脑梗死的发病密切相关,可能是有前景的治疗靶点。因此,我们从基因表达综合数据库中检索了数据集GSE16561和GSE22255,并从基因卡片数据库中提取了与细胞衰老和昼夜节律相关的基因。通过生物信息学分析,我们确定了与脑梗死中细胞衰老和昼夜节律相关的关键靶点,特别是CREBBP、FOS、CDK4、MMP9、PTEN和HIF1A。体外实验补充了这些发现,我们的结果表明,在脑梗死体外模型中,这些核心靶点的这些基因和蛋白质表达不同程度地升高。这些发现提供了有力证据,支持细胞衰老和昼夜节律相关基因在缺血性中风发病机制中的关键作用。

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