Plasma metabolites Xanthine, 4-Pyridoxate, and d-glutamic acid as novel potential biomarkers for pulmonary tuberculosis

Aim: We aimed to identify new plasma biomarkers for the diagnosis of Pulmonary tuberculosis. Background: Tuberculosis is an ancient infectious disease that remains one of the major global health problems. Until now, effective, convenient, and affordable methods for diagnosis of Pulmonary tuberculosis were still lacked. Objective: This study focused on construct a label-free LC-MS/MS based comparative proteomics between six tuberculosis patients and six healthy controls to identify differentially expressed proteins (DEPs) in plasma. Method: To reduce the influences of high-abundant proteins, albumin and globulin were removed from plasma samples using affinity gels. Then DEPs from the plasma samples were identified using a label-free Quadrupole-Orbitrap LC-MS/MS system. The results were analyzed by the protein database search algorithm SEQUEST-HT to identify mass spectra to peptides. The predictive abilities of combinations of host markers were investigated by general discriminant analysis (GDA), with leave-one-out cross-validation. Results: A total of 572 proteins were identified and 549 proteins were quantified. The threshold for differentially expressed protein was set as adjusted p-value < 0.05 and fold change ≥1.5 or ≤0.6667, 32 DEPs were found. ClusterVis, TBtools, and STRING were used to find new potential biomarkers of PTB. Six proteins, LY6D, DSC3, CDSN, FABP5, SERPINB12, and SLURP1, which performed well in the LOOCV method validation, were termed as potential biomarkers. The percentage of cross-validated grouped cases correctly classified and original grouped cases correctly classified is greater than or equal to 91.7%. Conclusion: We successfully identified five candidate biomarkers for immunodiagnosis of PTB in plasma, LY6D, DSC3, CDSN, SERPINB12, and SLURP1. Our work supported this group of proteins as potential biomarkers for pulmonary tuberculosis, and be worthy of further validation.

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Pulmonary Tuberculosis Treated with High Doses of INH plus Glutamic Acid

Diseases of the Chest ◽

10.1378/chest.37.4.382 ◽

1960 ◽

Vol 37 (4) ◽

pp. 382-389 ◽

Cited By ~ 1

Author(s):

FRANCIS O. SEGARRA ◽

DAVID S. SHERMAN

Keyword(s):

Pulmonary Tuberculosis ◽

Glutamic Acid ◽

High Doses

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Plasma metabolites in treatment-requiring retinopathy of prematurity: Potential biomarkers identified by metabolomics

Experimental Eye Research ◽

10.1016/j.exer.2020.108198 ◽

2020 ◽

Vol 199 ◽

pp. 108198

Author(s):

Yedi Zhou ◽

Yu Xu ◽

Xiang Zhang ◽

Peiquan Zhao ◽

Xiaoyun Gong ◽

...

Keyword(s):

Retinopathy Of Prematurity ◽

Plasma Metabolites ◽

Potential Biomarkers

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l-Histidine, arachidonic acid, biliverdin, and l-cysteine-glutathione disulfide as potential biomarkers for cured pulmonary tuberculosis

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2019.108980 ◽

2019 ◽

Vol 116 ◽

pp. 108980 ◽

Cited By ~ 8

Author(s):

Wen-Jing Yi ◽

Yu-Shuai Han ◽

Li-Liang Wei ◽

Li-Ying Shi ◽

Huai Huang ◽

...

Keyword(s):

Arachidonic Acid ◽

Pulmonary Tuberculosis ◽

Glutathione Disulfide ◽

Potential Biomarkers

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Capillary electrophoresis tandem mass spectrometry determination of glutamic acid and homocysteine’s metabolites: Potential biomarkers of amyotrophic lateral sclerosis

Talanta ◽

10.1016/j.talanta.2017.03.103 ◽

2017 ◽

Vol 170 ◽

pp. 63-68 ◽

Cited By ~ 13

Author(s):

Zuzana Cieslarova ◽

Fernando Silva Lopes ◽

Claudimir Lucio do Lago ◽

Marcondes Cavalcante França ◽

Ana Valéria Colnaghi Simionato

Keyword(s):

Mass Spectrometry ◽

Amyotrophic Lateral Sclerosis ◽

Capillary Electrophoresis ◽

Tandem Mass Spectrometry ◽

Glutamic Acid ◽

Tandem Mass ◽

Lateral Sclerosis ◽

Potential Biomarkers

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Discovery and identification of serum potential biomarkers for pulmonary tuberculosis using iTRAQ-coupled two-dimensional LC-MS/MS

PROTEOMICS ◽

10.1002/pmic.201300383 ◽

2014 ◽

Vol 14 (2-3) ◽

pp. 322-331 ◽

Cited By ~ 51

Author(s):

Dan-Dan Xu ◽

Dan-Feng Deng ◽

Xiang Li ◽

Li-Liang Wei ◽

Yan-Yuan Li ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Two Dimensional ◽

Potential Biomarkers

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Screening and identification of lncRNAs as potential biomarkers for pulmonary tuberculosis

Scientific Reports ◽

10.1038/s41598-017-17146-y ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 5

Author(s):

Zhong-liang Chen ◽

Li-Liang Wei ◽

Li-Ying Shi ◽

Meng Li ◽

Ting-Ting Jiang ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Screening And Identification ◽

Potential Biomarkers

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Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by altering plasma metabolites in hypercholesterolemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00136.2012 ◽

2012 ◽

Vol 303 (6) ◽

pp. E683-E694 ◽

Cited By ~ 13

Author(s):

Zhi-Jun Ou ◽

Li Li ◽

Xiao-Long Liao ◽

Yi-Ming Wang ◽

Xiao-Xia Hu ◽

...

Keyword(s):

Metabolic Profiling ◽

Atherosclerotic Lesion ◽

Time Dependent ◽

Negative Ion ◽

Plasma Metabolites ◽

Dependent Manner ◽

Mimetic Peptide ◽

Apolipoprotein A ◽

Long Chain ◽

Potential Biomarkers

An apolipoprotein A-I mimetic peptide, D-4F, has been shown to improve vasodilation and inhibit atherosclerosis in hypercholesterolemic low-density lipoprotein receptor-null (LDLr−/−) mice. To study the metabolic variations of D-4F ininhibiting atherosclerosis, metabonomics, a novel system biological strategy to investigate the pathogenesis, was developed. Female LDLr−/− mice were fed a Western diet and injected with or without D-4F intraperitoneally. Atherosclerotic lesion formation was measured, whereas plasma metabolic profiling was obtained on the basis of ultra-high-performance liquid chromatography in tandem with time-of-flight mass spectrometry operating in both positive and negative ion modes. Data were processed by multivariate statistical analysis to graphically demonstrate metabolic changes. The partial least-squares discriminate analysis model was validated with cross-validation and permutation tests to ensure the model's reliability. D-4F significantly inhibited the formation of atherosclerosis in a time-dependent manner. The metabolic profiling was altered dramatically in hypercholesterolemic LDLr−/− mice, and a significant metabolic profiling change in response to D-4F treatment was observed in both positive and negative ion modes. Thirty-six significantly changed metabolites were identified as potential biomarkers. A series of phospholipid metabolites, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), phosphatidylcholine (PC), phatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG), particularly the long-chain LysoPC, was elevated dramatically in hypercholesterolemic LDLr−/− mice but reduced by D-4F in a time-dependent manner. Quantitative analysis of LysoPC, LysoPE, PC, and DG using HPLC was chosen to validate the variation of these potential biomarkers, and the results were consistent with the metabonomics findings. Our findings demonstrated that D-4F may inhibit atherosclerosis by regulating phospholipid metabolites specifically by decreasing plasma long-chain LysoPC.

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