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新型冠状病毒肺炎:丝裂原活化蛋白激酶通路的一种可能作用

COVID-19: A Possible Contribution of the MAPK Pathway.

作者信息

Cusato Jessica, Manca Alessandra, Palermiti Alice, Mula Jacopo, Costanzo Martina, Antonucci Miriam, Trunfio Mattia, Corcione Silvia, Chiara Francesco, De Vivo Elisa Delia, Ianniello Alice, Ferrara Micol, Di Perri Giovanni, De Rosa Francesco Giuseppe, D'Avolio Antonio, Calcagno Andrea

机构信息

Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.

ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy.

出版信息

Biomedicines. 2023 May 16;11(5):1459. doi: 10.3390/biomedicines11051459.

Abstract

BACKGROUND

COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features.

METHODS

H-RAS, C-RAF, MAPK1, MAPK2, and ERK were quantified through ELISA, and genetic polymorphisms were evaluated through real-time PCR.

RESULTS

We prospectively recruited 201 individuals (158 positive and 43 negative for SARS-CoV-2): 35 were male, and their median age was 65 years. MAPK-related biomarker levels were increased in SARS-CoV-2-positive participants ( = 89) compared to negative ones ( = 29). Dyspnea was reported by 48%; this symptom was associated with PBMC C-RAF levels in positive participants ( = 0.022) and type of ventilation ( = 0.031). The highest degree of ventilation was used by 8% for invasive ventilation and 41% for continuous positive airway pressure (CPAP).

CONCLUSIONS

This is the first study that showed a possible contribution of MAPK-related biomarkers in affecting COVID-19 clinical features, and this may be relevant for identifying COVID-19 positive participants at risk of serious complications.

摘要

背景

新型冠状病毒肺炎(COVID-19)的特征是通过激活细胞内信号通路(如丝裂原活化蛋白激酶(MAPK))产生不受控制的炎症反应,并伴有促炎细胞因子大量生成。病毒能够利用MAPK信号通路为自身创造有利条件;该信号通路与重症COVID-19的相关性鲜有描述。本研究旨在量化参与MAPK信号通路的生物标志物,并阐明其在影响某些COVID-19相关临床特征方面可能发挥的作用。

方法

通过酶联免疫吸附测定(ELISA)对H-RAS、C-RAF、MAPK1、MAPK2和细胞外信号调节激酶(ERK)进行定量,并通过实时聚合酶链反应(PCR)评估基因多态性。

结果

我们前瞻性招募了201名个体(158名SARS-CoV-2检测呈阳性,43名检测呈阴性):其中35名为男性,中位年龄为65岁。与SARS-CoV-2检测呈阴性的参与者(n = 29)相比,检测呈阳性的参与者(n = 89)中MAPK相关生物标志物水平升高。48%的参与者报告出现呼吸困难;在检测呈阳性的参与者中,该症状与外周血单个核细胞(PBMC)C-RAF水平(P = 0.022)及通气类型(P = 0.031)相关。8%的参与者采用了最高级别的通气方式进行有创通气,41%的参与者采用持续气道正压通气(CPAP)。

结论

本研究首次表明MAPK相关生物标志物可能在影响COVID-19临床特征方面发挥作用,这可能有助于识别有严重并发症风险的COVID-19阳性参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/515c/10216575/162e1ab78501/biomedicines-11-01459-g001.jpg

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