Cell-free mitochondrial DNA quantification in ischemic stroke patients for non-invasive and real-time monitoring of disease status  

作　　者：Nusrath Fathima Sandhya Manorenj Sandeep Kumar Vishwakarma Aleem Ahmed Khan 

机构地区：[1]Central Laboratory for Stem Cell Research and Translational Medicine,Centre for Liver Research and Diagnostics,Deccan College of Medical Sciences,Hyderabad 500058,Telangana,India [2]Department of Neurology,Princess Esra Hospital,Deccan College of Medical Sciences,Hyderabad 500058,Telangana,India

出　　处：《World Journal of Translational Medicine》2022年第2期14-28,共15页世界转化医学杂志

摘　　要：BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and management.This study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA(cf-mtDNA)quantification and validation.AIM To evaluate the role of cf-mtDNA as s non-invasive,and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during treatment.METHODS This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset,and at 24 h and 72 h of treatment.Peripheral blood samples were collected from each study participant and plasma was separated using centrifugation.The cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction(RT-qPCR)of NADH-ubiquinone oxidoreductase chain 1(ND1)relative transcript expression levels.RESULTS Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading,as well as ND1 relative expression levels(P<0.0001).Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset(P<0.01).However,RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset(P<0.001).The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA quantification.Correlation analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive trend.CONCLUSION In summary,quantitative estimation of highly pure cf-mtDNA provides a simple,highly sensitive and specific,non-invasive,and affordable approach for real-time

关 键 词：Cell-free mitochondrial DNA NADH-ubiquinone oxidoreductase chain 1 Ischemic stroke Circulating biomarker National Institute of Health Stroke Scale score Stroke assessment Severity and outcome 

分 类 号：R73[医药卫生—肿瘤]