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与 COVID-19 感染相关的线粒体功能障碍的潜在生物标志物。

Potential Biomarkers of Mitochondrial Dysfunction Associated with COVID-19 Infection.

机构信息

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

Marche Polytechnic University, Ancona, Italy.

出版信息

Adv Exp Med Biol. 2023;1412:211-224. doi: 10.1007/978-3-031-28012-2_11.

Abstract

Mitochondria play crucial roles in modulating immune responses, and viruses can in turn moderate mitochondrial functioning. Therefore, it is not judicious to assume that clinical outcome experienced in patients with COVID-19 or long COVID may be influenced by mitochondrial dysfunction in this infection. Also, patients who are predisposed to mitochondrial respiratory chain (MRC) disorders may be more susceptible to worsened clinical outcome associated with COVID-19 infection and long COVID. MRC disorders and dysfunction require a multidisciplinary approach for their diagnosis of which blood and urinary metabolite analysis may be utilized, including the measurement of lactate, organic acid and amino acid levels. More recently, hormone-like cytokines including fibroblast growth factor-21 (FGF-21) have also been used to assess possible evidence of MRC dysfunction. In view of their association with MRC dysfunction, assessing evidence of oxidative stress parameters including GSH and coenzyme Q10 (CoQ10) status may also provide useful biomarkers for diagnosis of MRC dysfunction. To date, the most reliable biomarker available for assessing MRC dysfunction is the spectrophotometric determination of MRC enzyme activities in skeletal muscle or tissue from the disease-presenting organ. Moreover, the combined use of these biomarkers in a multiplexed targeted metabolic profiling strategy may further improve the diagnostic yield of the individual tests for assessing evidence of mitochondrial dysfunction in patients pre- and post-COVID-19 infection.

摘要

线粒体在调节免疫反应方面起着至关重要的作用,而病毒反过来也可以调节线粒体的功能。因此,不能想当然地认为 COVID-19 或长新冠患者的临床结果可能受到这种感染中线粒体功能障碍的影响。此外,易患线粒体呼吸链(MRC)疾病的患者可能更容易受到与 COVID-19 感染和长新冠相关的临床结果恶化的影响。MRC 疾病和功能障碍需要采用多学科方法进行诊断,其中可能会利用血液和尿液代谢物分析,包括测量乳酸、有机酸和氨基酸水平。最近,包括成纤维细胞生长因子 21(FGF-21)在内的类激素细胞因子也被用于评估可能存在的 MRC 功能障碍的证据。鉴于它们与 MRC 功能障碍有关,评估包括 GSH 和辅酶 Q10(CoQ10)状态在内的氧化应激参数的证据也可能为 MRC 功能障碍的诊断提供有用的生物标志物。迄今为止,评估 MRC 功能障碍最可靠的生物标志物是通过分光光度法测定骨骼肌或疾病表现器官组织中的 MRC 酶活性。此外,在多重靶向代谢谱分析策略中联合使用这些生物标志物可能会进一步提高评估 COVID-19 感染前后患者线粒体功能障碍证据的各个测试的诊断效果。

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