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使用气相色谱-质谱联用飞行时间质谱仪(非靶向方法)对斯普拉格-道利大鼠感染的代谢组学进行的初步见解。

Preliminary insights on the metabolomics of infection in Sprague Dawley rats using GCxGC-TOF-MS (untargeted approach).

作者信息

Ndlovu I S, Silas Ekuyikeno, Tshilwane S I, Chaisi M, Vosloo A, Mukaratirwa S

机构信息

School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.

Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

出版信息

Front Mol Biosci. 2023 Feb 17;10:1128542. doi: 10.3389/fmolb.2023.1128542. eCollection 2023.

Abstract

infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into infected group ( = 36) and the non-infected control ( = 18). Results from the study showed that the metabolic signature of infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.

摘要

全球范围内都有感染的记录,除南极洲外,在野生动物和/或家畜中均检测到感染。目前关于宿主在感染期间的代谢反应以及可用于疾病诊断的感染生物标志物的信息较少。本研究旨在应用非靶向代谢组学方法来鉴定生物标志物,包括感染的斯普拉格-道利大鼠血清中的代谢反应。54只雄性斯普拉格-道利大鼠被随机分为感染组(n = 36)和未感染对照组(n = 18)。研究结果表明,感染的代谢特征包括甲基组氨酸代谢富集、肝脏尿素循环紊乱、三羧酸循环受阻以及糖异生代谢上调。观察到的代谢途径紊乱归因于寄生虫在迁移到肌肉过程中所产生的影响,导致旋毛虫感染动物体内氨基酸中间体下调,从而影响能量产生和生物分子降解。研究得出结论,感染导致氨基酸、哌可酸、组氨酸和尿素上调,以及葡萄糖和内消旋赤藓醇上调。此外,感染导致脂肪酸、视黄酸和乙酸上调。这些发现凸显了代谢组学作为一种新方法在宿主-病原体相互作用的基础研究以及疾病进展和预后方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2a/9983363/41dcbe1f1400/fmolb-10-1128542-g001.jpg

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