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采用 GCxGC-TOF/MS 技术对南非儿科队列中 HIV 的 CSF 代谢谱进行探索性研究。

An exploratory investigation of the CSF metabolic profile of HIV in a South African paediatric cohort using GCxGC-TOF/MS.

机构信息

Department of Biochemistry, Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, North West, South Africa.

Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.

出版信息

Metabolomics. 2024 Mar 1;20(2):33. doi: 10.1007/s11306-024-02098-y.

Abstract

INTRODUCTION

Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.

AIM AND OBJECTIVE

The aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.

RESULTS

The results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.

CONCLUSIONS

This study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.

摘要

简介

由于难以获取小儿 HIV 的脑脊液 (CSF) 样本,因此很少有研究尝试描述神经代谢失调。

目的和目标

本探索性研究旨在使用 GCxGC-TOF/MS 描述南非小儿队列的 CSF 神经代谢状态。该研究纳入了 54 例儿科病例(<12 岁)、42 例 HIV 阴性对照和 12 例 HIV 阳性个体。

结果

结果显示 HIV 感染组存在明显的代谢改变。在 PLS-DA 模型中,18 种代谢物可显著区分 HIV 感染组和对照组。此外,倍数变化分析、Mann-Whitney U 检验和效应大小测量验证了这些发现。值得注意的是,乳糖、肌醇和甘油虽然单独通过 p 值不显著,但基于效应大小显示出实际意义。

结论

本研究提供了关于 HIV 对代谢途径影响的有价值的见解,包括对肠道和血脑屏障的损害、生物能量过程的中断、神经胶质增生以及潜在的抗逆转录病毒治疗标志物。然而,该研究认识到一些局限性,特别是样本量有限且缺乏验证队列。尽管存在这些限制,但该研究对小儿 HIV 研究的关注罕见,突显了其发现的重要性和独特贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b8/10907482/841a6e9ef58a/11306_2024_2098_Fig1_HTML.jpg

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