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极早期高血压性脑出血(HICH)中mRNA生物标志物的鉴定

Identification of mRNA biomarkers in extremely early hypertensive intracerebral hemorrhage (HICH).

作者信息

Gao Haidong, Zhang Jian, Wang Xinjun, Shou Jixin, Wang Jianye, Yang Peng

机构信息

Department of Neurosurgery, Zhengzhou University Fifth Affiliated Hospital, Erqi District, No.3, Rehabilitation Front Street, Zhengzhou, Henan, 45000, China.

出版信息

Proteome Sci. 2024 Nov 30;22(1):12. doi: 10.1186/s12953-024-00237-w.

DOI:10.1186/s12953-024-00237-w
PMID:39616335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11607980/
Abstract

INTRODUCTION

Hypertensive intracerebral hemorrhage (HICH) stands out as a critical complication of primary hypertension. Consequently, investigating messenger RNA (mRNA) biomarkers becomes imperative, offering potential targets. This study is conducted for elucidating the expression profile of blood mRNA biomarkers in HICH.

METHODS

Twenty-five HICH patients were constituted the HICH group.Twenty-two healthy volunteers recruited and comprised the control group. Peripheral blood cells were extracted to identify candidate mRNA. The identified differential expressions of genes between the two groups were validated, and the potential associations between these differentially expressed genes and adverse events were analyzed. GO and KEGG enrichment of DEGs, Weighted Gene Co-expression Network and Protein Interaction Network were established. target mRNA was screened.

RESULTS

The study identified 3163 differentially expressed genes in HICH. 8 candidate mRNA (SPI1, HK3, HCK, SYK, CD14, FCER1G, CYBB, FGR) were pinpointed. Associations with pathways affecting HICH development included HIF-1 signaling, NF-kappa B signaling, and C-type lectin receptor signaling. In the HICH group, higher expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR, and lower SPI1 expression compared to the control group. HICH patients experienced high rates of complications: pulmonary infection (84%), epilepsy (16%), enlarged hematoma (20%), gastrointestinal bleeding (48%), malnutrition (84%), and lower limb deep vein thrombosis (DVT) (12%). Factors contributing to pulmonary infection included age and elevated expression of HCK, SYK, CD14, and FGR. SPI1 was associated with epilepsy, while its lower expression correlated with hematoma enlargement. Gastrointestinal bleeding was linked to increased cerebral hemorrhage. Malnutrition was associated with higher age, and expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR. Patients with lower limb DVT had elevated expressions of the identified genes.

CONCLUSION

In hypertensive intracerebral hemorrhage, there are elevated expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR, along with reduced expression of SPI1. Furthermore, age, along with elevated expressions of HCK, SYK, CD14, and FGR, serves as influencing factors contributing to pulmonary infection in patients.

摘要

引言

高血压性脑出血(HICH)是原发性高血压的一种关键并发症。因此,研究信使核糖核酸(mRNA)生物标志物势在必行,可为其提供潜在靶点。本研究旨在阐明HICH患者血液mRNA生物标志物的表达谱。

方法

选取25例HICH患者组成HICH组,招募22名健康志愿者组成对照组。提取外周血细胞以鉴定候选mRNA。对两组之间鉴定出的基因差异表达进行验证,并分析这些差异表达基因与不良事件之间的潜在关联。建立差异表达基因(DEGs)的基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析、加权基因共表达网络和蛋白质相互作用网络,筛选目标mRNA。

结果

本研究在HICH中鉴定出3163个差异表达基因,确定了8个候选mRNA(SPI1、HK3、HCK、SYK、CD14、FCER1G、CYBB、FGR)。与影响HICH发展的信号通路相关的有缺氧诱导因子-1(HIF-1)信号通路、核因子-κB(NF-κB)信号通路和C型凝集素受体信号通路。在HICH组中,与对照组相比,HK3、HCK、SYK、CD14、FCER1G、CYBB和FGR的表达较高,而SPI1的表达较低。HICH患者并发症发生率较高:肺部感染(84%)、癫痫(16%)、血肿扩大(20%)、胃肠道出血(48%)、营养不良(84%)和下肢深静脉血栓形成(DVT)(12%)。导致肺部感染的因素包括年龄以及HCK、SYK、CD14和FGR的表达升高。SPI1与癫痫有关,其低表达与血肿扩大相关。胃肠道出血与脑出血增加有关。营养不良与年龄较大以及HK3、HCK、SYK、CD14、FCER1G、CYBB和FGR的表达有关。下肢DVT患者所鉴定基因的表达升高。

结论

在高血压性脑出血中,HK3、HCK、SYK、CD14、FCER1G、CYBB和FGR表达升高,SPI1表达降低。此外,年龄以及HCK、SYK、CD14和FGR的表达升高是导致患者肺部感染的影响因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb10/11607980/a4e105463319/12953_2024_237_Fig8_HTML.jpg
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CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans.CD14 信号转导介导木糖氧化无色杆菌引起的肺部免疫病理学和小鼠死亡。
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