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用于回顾性生物剂量测定和急性健康效应预测的早期分子标志物。

Early molecular markers for retrospective biodosimetry and prediction of acute health effects.

作者信息

Abend M, Blakely W F, Ostheim P, Schuele S, Port M

机构信息

Bundeswehr Institute of Radiobiology, Munich, Germany.

Armed Forces Radiobiology Research Institute, Bethesda, MD, United States of America.

出版信息

J Radiol Prot. 2022 Jan 25;42(1). doi: 10.1088/1361-6498/ac2434.

Abstract

Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1-3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.g. radiation quality, dose, dose rate and most importantly over time. Changes over time are in particular challenging and demand certain strategies to deal with. With this review, we provide an overview and will focus on already identified and used mRNA GE and protein markers of the peripheral blood related to the ARS. These molecules are examined in light of 'ideal' characteristics of a biomarkers (e.g. easy accessible, early response, signal persistency) and the validation degree. Finally, we present strategies on the use of these markers considering challenges as their variation over time and future developments regarding e.g. origin of samples, point of care and high-throughput diagnosis.

摘要

辐射后数小时和数天内发生的辐射诱导生物学变化可潜在地用于暴露重建(回顾性剂量测定)或预测随后发生的急性或慢性健康影响。分子蛋白质或基因表达(GE)(mRNA)标志物的优势在于它们能够进行早期(辐射后1 - 3天)、高通量和即时诊断,这对于在放射或核场景中预测急性放射综合征(ARS)是必需的。在大多数情况下,这些分子标志物对于诸如辐射质量、剂量、剂量率等暴露特征,尤其是随时间的变化,反应不同。随时间的变化特别具有挑战性,需要特定的应对策略。通过本综述,我们提供了一个概述,并将重点关注已确定和使用的与ARS相关的外周血mRNA GE和蛋白质标志物。根据生物标志物的“理想”特征(例如易于获取、早期反应、信号持续性)和验证程度对这些分子进行了研究。最后,考虑到这些标志物随时间的变化以及例如样本来源、即时诊断和高通量诊断等方面的未来发展所带来的挑战,我们提出了使用这些标志物的策略。

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