Urinary Metabolomics: A New Journey for Biomarker Discovery

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Advances in Metabolomics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 4889

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Guest Editor
Phelps Health, Missouri University of Science and Technology, Rolla, MO, USA
Interests: urinary metabolomics; cancer biomarkers; traumatic brain injury biomarkers; LC-MS/MS; analytical method development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of urinary metabolomics is gaining popularity as a robust platform for biomarker discovery owing to recent advances in analytical techniques and their seamless integration with existing clinical laboratory workflows. Moreover, urine as a specimen type offers several distinct advantages for biomarker development and screening, including the ability to be sampled noninvasively in large volumes involving a comparatively simple matrix.

The recent proliferation of advanced analytical methods for targeted and untargeted metabolomics has revealed an increasing number of urinary metabolites implicated in pathogenesis and disease progression. These metabolites have the potential to serve as novel biomarkers for disease risk stratification, screening and detection, as well as monitoring therapeutic response, among other clinical applications.

This Special Issue is dedicated to highlighting the newest advances in urinary metabolomics and current efforts to overcome barriers and challenges. Topics related to analytical techniques and approaches to metabolomics profiling, biomarker development and validation through translational and clinical research, and the variability of urinary metabolites in response to various internal and external factors are welcomed.

Dr. Casey Burton
Guest Editor

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Keywords

  • urinary metabolomics
  • biomarker discovery
  • biomarker validation

Published Papers (3 papers)

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Research

16 pages, 6184 KiB  
Article
Metabolic Profile Analysis of Designer Benzodiazepine Etizolam in Zebrafish and Human Liver Microsomes
by Zhaowei Jie, Shiyang Qin, Wenfang Zhang, Jifen Wang, Jianghai Lu, Ge Qin, Xiaolong Hou and Peng Xu
Metabolites 2023, 13(6), 699; https://doi.org/10.3390/metabo13060699 - 27 May 2023
Cited by 1 | Viewed by 1314
Abstract
As one of the most widely abused designer benzodiazepines worldwide, Etizolam is characterized by its high addiction potential, low production cost, and difficulty in detection. Due to the rapid metabolism of Etizolam in the human body, the probability of detecting the Etizolam parent [...] Read more.
As one of the most widely abused designer benzodiazepines worldwide, Etizolam is characterized by its high addiction potential, low production cost, and difficulty in detection. Due to the rapid metabolism of Etizolam in the human body, the probability of detecting the Etizolam parent drug in actual case samples by forensic personnel is low. Therefore, without detecting the parent drug, analysis of Etizolam metabolites can help forensic personnel provide references and suggestions on whether the suspect has taken Etizolam. This study simulates the objective metabolic process of the human body. It establishes a zebrafish in vivo metabolism model and a human liver microsome in vitro metabolism model to analyze the metabolic characteristics of Etizolam. A total of 28 metabolites were detected in the experiment, including 13 produced in zebrafish, 28 produced in zebrafish urine and feces, and 17 produced in human liver microsomes. The UPLC-Q-Exactive-MS technology was used to analyze the structures and related metabolic pathways of Etizolam metabolites in zebrafish and human liver microsomes, and a total of 9 metabolic pathways were identified, including monohydroxylation, dihydroxylation, hydration, desaturation, methylation, oxidative deamination to alcohol, oxidation, reduction acetylation, and glucuronidation. Among them, metabolites involving hydroxylation reactions (including monohydroxylation and dihydroxylation) accounted for 57.1% of the total number of potential metabolites, indicating that hydroxylation may be the major metabolic pathway of Etizolam. Based on the response values of each metabolite, monohydroxylation (M1), desaturation (M19), and hydration (M16) were recommended as potential biomarkers for Etizolam metabolism. The experimental results provide reference and guidance for forensic personnel in identifying Etizolam use in suspects. Full article
(This article belongs to the Special Issue Urinary Metabolomics: A New Journey for Biomarker Discovery)
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10 pages, 1140 KiB  
Article
Repeated Low-Level Blast Exposure Alters Urinary and Serum Metabolites
by Austin Sigler, Jiandong Wu, Annalise Pfaff, Olajide Adetunji, Paul Nam, Donald James, Casey Burton and Honglan Shi
Metabolites 2023, 13(5), 638; https://doi.org/10.3390/metabo13050638 - 8 May 2023
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Abstract
Repeated exposure to low-level blast overpressures can produce biological changes and clinical sequelae that resemble mild traumatic brain injury (TBI). While recent efforts have revealed several protein biomarkers for axonal injury during repetitive blast exposure, this study aims to explore potential small molecule [...] Read more.
Repeated exposure to low-level blast overpressures can produce biological changes and clinical sequelae that resemble mild traumatic brain injury (TBI). While recent efforts have revealed several protein biomarkers for axonal injury during repetitive blast exposure, this study aims to explore potential small molecule biomarkers of brain injury during repeated blast exposure. This study evaluated a panel of ten small molecule metabolites involved in neurotransmission, oxidative stress, and energy metabolism in the urine and serum of military personnel (n = 27) conducting breacher training with repeated exposure to low-level blasts. The metabolites were analyzed using HPLC—tandem mass spectrometry, and the Wilcoxon signed-rank test was used for statistical analysis to compare the levels of pre-blast and post-blast exposures. Urinary levels of homovanillic acid (p < 0.0001), linoleic acid (p = 0.0030), glutamate (p = 0.0027), and serum N-acetylaspartic acid (p = 0.0006) were found to be significantly altered following repeated blast exposure. Homovanillic acid concentration decreased continuously with subsequent repeat exposure. These results suggest that repeated low-level blast exposures can produce measurable changes in urine and serum metabolites that may aid in identifying individuals at increased risk of sustaining a TBI. Larger clinical studies are needed to extend the generalizability of these findings. Full article
(This article belongs to the Special Issue Urinary Metabolomics: A New Journey for Biomarker Discovery)
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13 pages, 2484 KiB  
Article
Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon
by Madeleine Eunice Betouke Ongwe, Isabelle Kohler, Mikhael D. Manurung, Aswin Verhoeven, Rico Derks, Jacqueline J. Janse, Yoanne D. Mouwenda, Peter G. Kremsner, Ayola A. Adegnika, Bertrand Lell, Bart Everts, Oleg A. Mayboroda and Maria Yazdanbakhsh
Metabolites 2022, 12(12), 1224; https://doi.org/10.3390/metabo12121224 - 6 Dec 2022
Cited by 2 | Viewed by 1696
Abstract
The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of [...] Read more.
The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-naïve Europeans, who were all challenged with direct venous inoculation of live P. falciparum sporozoïtes (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas. Full article
(This article belongs to the Special Issue Urinary Metabolomics: A New Journey for Biomarker Discovery)
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