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非靶向血清代谢组学分析在小鼠模型中用于早期感染检测。

Untargeted serum metabolomic profiling for early detection of infection in mouse model.

机构信息

Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.

Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Front Cell Infect Microbiol. 2022 Aug 18;12:910177. doi: 10.3389/fcimb.2022.910177. eCollection 2022.

Abstract

Mekong schistosomiasis is a parasitic disease caused by blood flukes in the Lao People's Democratic Republic and in Cambodia. The standard method for diagnosis of schistosomiasis is detection of parasite eggs from patient samples. However, this method is not sufficient to detect asymptomatic patients, low egg numbers, or early infection. Therefore, diagnostic methods with higher sensitivity at the early stage of the disease are needed to fill this gap. The aim of this study was to identify potential biomarkers of early schistosomiasis using an untargeted metabolomics approach. Serum of uninfected and -infected mice was collected at 2, 4, and 8 weeks post-infection. Samples were extracted for metabolites and analyzed with a liquid chromatography-tandem mass spectrometer. Metabolites were annotated with the MS-DIAL platform and analyzed with Metaboanalyst bioinformatic tools. Multivariate analysis distinguished between metabolites from the different experimental conditions. Biomarker screening was performed using three methods: correlation coefficient analysis; feature important detection with a random forest algorithm; and receiver operating characteristic (ROC) curve analysis. Three compounds were identified as potential biomarkers at the early stage of the disease: heptadecanoyl ethanolamide; picrotin; and theophylline. The levels of these three compounds changed significantly during early-stage infection, and therefore these molecules may be promising schistosomiasis markers. These findings may help to improve early diagnosis of schistosomiasis, thus reducing the burden on patients and limiting spread of the disease in endemic areas.

摘要

湄公血吸虫病是一种寄生虫病,由老挝人民民主共和国和柬埔寨的血吸虫引起。诊断血吸虫病的标准方法是从患者样本中检测寄生虫卵。然而,这种方法不足以检测无症状患者、低卵数或早期感染。因此,需要具有更高敏感性的诊断方法来填补这一空白。本研究旨在使用非靶向代谢组学方法鉴定早期血吸虫病的潜在生物标志物。在感染后 2、4 和 8 周收集未感染和感染的小鼠的血清。提取样本中的代谢物,并使用液相色谱-串联质谱仪进行分析。使用 MS-DIAL 平台对代谢物进行注释,并使用 Metaboanalyst 生物信息学工具进行分析。多变量分析区分了不同实验条件下的代谢物。使用三种方法进行生物标志物筛选:相关系数分析;随机森林算法的特征重要性检测;和接收器操作特性 (ROC) 曲线分析。鉴定出三种化合物作为疾病早期的潜在生物标志物:十七烷酰乙醇酰胺;胡椒碱;和茶碱。这三种化合物在早期感染期间的水平发生了显著变化,因此这些分子可能是有前途的血吸虫病标志物。这些发现可能有助于改善血吸虫病的早期诊断,从而减轻患者的负担,并限制疾病在流行地区的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a630/9433908/9e42ad0aa658/fcimb-12-910177-g001.jpg

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