title: Characterization of rational biomarkers accompanying fever in yeast-induced pyrexia rats using urine metabolic footprint analysis.
abstract: Fever is a prominent feature of diseases and is an ongoing process that is always accompanied by metabolic changes in the body system. Despite the success of temperature regulation theory, the underlying biological process remains unclear. To truly understand the nature of the febrile response, it is crucial to confirm the biomarkers during the entire biological process. In the current study, a 73-h metabolic footprint analysis of the urine from yeast-induced pyrexia rats was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Potential biomarkers were selected using orthogonal partial least squares-discriminate analysis (OPLS-DA), the rational biomarkers were verified by Pearson correlation analysis, and the predictive power was evaluated using receiver operator characteristic (ROC) curves. A metabolic network constructed using traditional Chinese medicine (TCM) grammar systems was used to validate the rationality of the verified biomarkers. Finally, five biomarkers, including indoleacrylic acid, 3-methyluridine, tryptophan, nicotinuric acid and PI (37:3), were confirmed as rational biomarkers because their correlation coefficients were all greater than 0.87 and because all of the correlation coefficients between any pair of these biomarkers were higher than 0.75. The areas under the ROC curves were all greater than 0.84, and their combined predictive power was considered reliable because the greatest area under the ROC curve was 0.968. A metabolic network also demonstrated the rationality of these five biomarkers. Therefore, these five metabolites can be adopted as rational biomarkers to reflect the process of the febrile response in inflammation-induced pyrexia.
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Guo
authors.affiliation: Key Laboratory of TCM-Information Engineering of State Administration of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Peng
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of TCM-Information Engineering of State Administration of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, PR China.
authors.forename: Zhaozhou
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Key Laboratory of TCM-Information Engineering of State Administration of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, PR China. Electronic address: wangyun@bucm.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China. Electronic address: gaoxiaoyan0913@sina.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of TCM-Information Engineering of State Administration of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, PR China.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Qiao
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005334:Fever / Q000209:etiology / Q000378:metabolism*; D016018:Least-Squares Analysis; D008297:Male; D008516:Medicine, Chinese Traditional; D053858:Metabolic Networks and Pathways; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae; D052616:Solid Phase Extraction; D014364:Tryptophan / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014364:Tryptophan
keywords: Biomarkers; Metabolic footprint analysis; Quadrupole time-of-flight mass spectrometry; Ultra performance liquid chromatography; Yeast-induced pyrexia