对抗血液兴奋剂的新一代“组学”方法。

Medicine and sport science Pub Date : 2017-01-01 Epub Date: 2017-06-01 DOI:10.1159/000470919
Guan Wang, Antonia Karanikolou, Ioanna Verdouka, Theodore Friedmann, Yannis Pitsiladis
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引用次数: 12

摘要

尽管被世界反兴奋剂机构(WADA)禁止,血液操作,如使用重组人红细胞生成素和输血,是运动员用来提高成绩的一种众所周知的方法。由于物质/方法的检测窗口短、样品采集时间短以及使用复杂的掩蔽策略,直接检测非法血液操作在一定程度上取得了成功。作为回应,世界反兴奋剂机构于2009年推出了运动员生物护照(ABP),这是一种个性化的纵向监测方法,主要测试兴奋剂的血液学生物标志物,以识别运动员反应的非典型变异性,突出潜在的兴奋剂违规行为。虽然ABP的实施是追求清洁/无毒品运动的令人鼓舞的一步,但这种检测方法有一些局限性。为了降低被ABP检测到的风险,运动员现在正在使用微剂量的违禁血液促进物质来防止血液学生物标志物的异常波动,从而降低ABP检测方法的灵敏度。包括我们自己的实验室在内的许多实验室最近的研究都证实了转录组微阵列的潜力,它可以揭示血液操作后基因表达的明显变化,从而增强ABP。因此,迫切需要加强涉及转录组学和其他最先进的分子方法的研究,这些方法统称为“组学”,例如蛋白质组学(蛋白质)和代谢组学(代谢物)。以确定新的甚至更强大的血液操作分子特征,这些特征可以与ABP结合使用,有趣的是,甚至可以作为一个独立的测试。
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Next Generation "Omics" Approaches in the "Fight" against Blood Doping.

Despite being prohibited by the World Anti-Doping Agency (WADA), blood manipulations such as the use of recombinant human erythropoietin and blood transfusions are a well-known method used by athletes to enhance performance. Direct detection of illicit blood manipulation has been partially successful due to the short detection window of the substances/methods, sample collection timing, and the use of sophisticated masking strategies. In response, WADA introduced the athlete biological passport (ABP) in 2009, which is an individualised longitudinal monitoring approach that tests primarily haematologic biomarkers of doping in order to identify atypical variability in response(s) in athletes, highlighting a potential doping violation. Although the implementation of the ABP has been an encouraging step forward in the quest for clean/drug-free sport, this detection method has some limitations. To reduce the risk of being detected by the ABP method, athletes are now resorting to microdoses of prohibited blood boosting substances to prevent abnormal fluctuations in haematologic biomarkers, thereby reducing the sensitivity of the ABP detection method. Recent studies from numerous laboratories, including our own, have confirmed the potential of transcriptomic microarrays, which can reveal distinct changes in gene expression after blood manipulations, to enhance the ABP. There is, therefore, an urgent need to intensify research efforts that involve transcriptomics and other state-of-the-art molecular methods, collectively known as "omics", e.g., proteomics (proteins) and metabolomics (metabolites), in order to identify new and even more robust molecular signatures of blood manipulation that can be used in combination with the ABP and, intriguingly, even as a stand-alone test.

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Sport, Society, and Anti-Doping Policy: An Ethical Overview. Structure and Development of the List of Prohibited Substances and Methods. Integration of the Forensic Dimension into Anti-Doping Strategies. How to Develop Intelligence Gathering in Efficient and Practical Anti-Doping Activities. Achievements and Challenges in Anti-Doping Research.
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