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代谢组学可检测到与HIV/高效抗逆转录病毒疗法相关的氧化应激。

HIV/HAART-associated oxidative stress is detectable by metabonomics.

作者信息

Williams Aurelia A, Sitole Lungile J, Meyer Debra

机构信息

Human Metabolomics, North-West University, Private Bag X6001, Box 269, Potchefstroom, 2531, South Africa.

出版信息

Mol Biosyst. 2017 Oct 24;13(11):2202-2217. doi: 10.1039/c7mb00336f.

Abstract

Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase. Data from many of these studies identified metabolic markers indicative of HIV-induced OS, usually as an outcome of an untargeted metabonomics study. Untargeted studies cast a wide net for any and all detectable metabolites in complex mixtures. Given the prevalence of OS during HIV infection and antiviral treatment, it is perhaps not surprising that indicators of this malady would become evident during metabolite identification. At times, targeted studies for specific (non-OS) metabolites would also yield OS markers as an outcome. This review examines the findings of these studies by first providing the necessary background information on OS and the main ways in which free radicals/reactive oxygen species (ROS) produced during OS, cause biomolecular damage. This is followed by information on the biomarkers which come about as a result of free radical damage and the techniques used for assaying these stress indicators. The established links between elevated ROS and lowered antioxidants during HIV infection and the subsequent use of HAART is then presented followed by a review of the OS markers detected in HIV metabonomic studies to date. We identify gaps in HIV/HAART-associated OS research and finally suggest how these research gaps can be addressed through metabonomic analysis, specifically targeting the multiple markers of HIV-induced OS.

摘要

慢性人类免疫缺陷病毒(HIV)感染,单独或与高效抗逆转录病毒疗法(HAART)联合使用时,都与氧化应激(OS)密切相关。大多数证明HIV感染者存在氧化还原失衡的研究都是使用传统生化方法进行的。这些方法的一个主要缺点是在一个样本中同时检测多种OS标志物的能力有限,而代谢组学可以解决这一问题。利用HAART队列中的生物流体作为研究来源的HIV代谢组学研究正在增加。许多这些研究的数据确定了指示HIV诱导的OS的代谢标志物,通常是作为非靶向代谢组学研究的结果。非靶向研究对复杂混合物中的任何和所有可检测代谢物进行广泛筛查。鉴于HIV感染和抗病毒治疗期间OS的普遍性,在代谢物鉴定过程中这种疾病的指标变得明显也许并不奇怪。有时,针对特定(非OS)代谢物的靶向研究也会产生OS标志物作为结果。本综述首先提供关于OS的必要背景信息以及OS期间产生的自由基/活性氧(ROS)导致生物分子损伤的主要方式,以此来审视这些研究的结果。接下来是关于自由基损伤产生的生物标志物以及用于检测这些应激指标的技术的信息。然后介绍HIV感染期间ROS升高和抗氧化剂降低之间已确立的联系以及随后使用HAART的情况,接着回顾迄今为止在HIV代谢组学研究中检测到的OS标志物。我们确定了HIV/HAART相关OS研究中的差距,最后提出如何通过代谢组学分析来解决这些研究差距,特别是针对HIV诱导的OS的多种标志物。

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