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金黄地鼠内脏利什曼病的代谢特征和生物标志物筛选。

Metabolic characterization and biomarkers screening for visceral leishmaniasis in golden hamsters.

机构信息

Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Department of Human Anatomy, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China.

出版信息

Acta Trop. 2022 Jan;225:106222. doi: 10.1016/j.actatropica.2021.106222. Epub 2021 Oct 30.

DOI:10.1016/j.actatropica.2021.106222
PMID:34757045
Abstract

A better understanding of the changes in metabolic molecules during visceral leishmaniasis (VL) is essential to develop new strategies for diagnosis and treatment. Previous metabolomics studies on Leishmania have increased our knowledge of leishmaniasis and its causative pathogen. As these studies were mainly carried out in vitro, to go further, we conducted this global metabolomics analysis on the serum of golden hamsters. Serum samples were detected over a time course of 2, 4, 8 and 12 weeks post infection. Our results revealed that under extensively disturbed metabolomes between the infection group and controls, glycerophospholipid (GPL) metabolism was most affected over the infection time, followed by α-linoleic acid metabolism and arachidonic acid metabolism. Within GPLs, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were found to be significantly increased, while their enzyme-catalysed metabolites lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) showed no significant changes. Moreover, eight differential metabolites were selected. The ability of these metabolites to be used as a diagnostic biomarker panel was supported by receiver operating characteristic (ROC) analysis. Our findings revealed that GPL metabolism might play an important role in the response of the host to Leishmania infection. The metabolism of PC and PE might be crucial in the in vivo progression of VL. The panel of eight potential biomarkers might contribute to the diagnosis of VL.

摘要

深入了解内脏利什曼病(VL)期间代谢分子的变化对于开发新的诊断和治疗策略至关重要。以前对利什曼原虫的代谢组学研究增加了我们对利什曼病及其病原体的认识。由于这些研究主要在体外进行,为了更进一步,我们在金黄地鼠的血清中进行了这项全局代谢组学分析。在感染后 2、4、8 和 12 周的时间过程中检测血清样本。我们的结果表明,在感染组和对照组之间广泛失调的代谢组中,甘油磷脂(GPL)代谢在感染时间内受到的影响最大,其次是α-亚麻酸代谢和花生四烯酸代谢。在 GPL 中,发现磷脂酰胆碱(PC)和磷脂酰乙醇胺(PE)显著增加,而其酶催化代谢物溶血磷脂酰胆碱(LPC)和溶血磷脂酰乙醇胺(LPE)没有明显变化。此外,还选择了八个差异代谢物。ROC 分析支持这些代谢物作为诊断生物标志物组合的能力。我们的研究结果表明,GPL 代谢可能在宿主对利什曼原虫感染的反应中起重要作用。PC 和 PE 的代谢在 VL 的体内进展中可能至关重要。这组八个潜在的生物标志物可能有助于 VL 的诊断。

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