Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Metabolomics study of COVID-19 patients in four different clinical stages

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Jan. 31, 2022

Abstract SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the strain causing pandemic COVID-19 (coronavirus disease 2019). To understand pathobiology of in humans it necessary to unravel metabolic changes that are produced individuals once infection has taken place. The goal this work provide new information about altered biomolecule profile and with biological pathways patients different clinical situations due infection. This done via metabolomics using HPLC–QTOF–MS analysis plasma samples at COVID-diagnose from a total 145 adult patients, divided into stages based on their subsequent outcome (25 negative controls (non-COVID); 28 positive asymptomatic not requiring hospitalization; 27 mild defined by time hospital lower than 10 days; 36 severe over 20 days and/or admission ICU; 29 fatal or deceased). Moreover, follow up between 2 3 months after discharge were also obtained hospitalized prognosis. final biomarkers can help better how illness evolves predict patient could progress metabolites an early stage In present work, several found as potential distinguish end-stage early-stage (or non-COVID) groups. These mainly involved metabolism carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids purines, but omeprazole. addition, levels these decreased “normal” values discharge, suggesting some them prognosis diagnose.

Language: Английский

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Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Metabolomics, Journal Year: 2021, Volume and Issue: 18(1)

Published: Dec. 20, 2021

Abstract Introduction The diagnosis of COVID-19 is normally based on the qualitative detection viral nucleic acid sequences. Properties host response are not measured but key in determining outcome. Although metabolic profiles well suited to capture state, most metabolomics studies either underpowered, measure only a restricted subset metabolites, compare infected individuals against uninfected control cohorts that suitably matched, or do provide compact predictive model. Objectives Here we well-powered, untargeted assessment 120 patient samples acquired at hospital admission. study aims predict patient’s infection severity (i.e., mild severe) and potential outcome discharged deceased). Methods High resolution UHPLC-MS/MS analysis was performed serum using both positive negative ionization modes. A 20 intermediary metabolites were selected univariate statistical significance multiple predictor Bayesian logistic regression model created. Results predictors for their relevant biological function include deoxycytidine ureidopropionate (indirectly reflecting load), kynurenine (reflecting inflammatory response), short chain acylcarnitines (energy metabolism) among others. Currently, this approach predicts with Monte Carlo cross validated area under ROC curve 0.792 (SD 0.09) 0.793 0.08), respectively. blind validation an additional 90 patients predicted AUC 0.83 (CI 0.74–0.91) 0.76 0.67–0.86). Conclusion Prognostic tests markers discussed paper could allow improvement planning treatment.

Language: Английский

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COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2414 - 2414

Published: Feb. 22, 2022

Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale understand pathobiology of SARS-CoV-2 infection and its replication into human cells. The application omics techniques has addressed every level application, from detection mutations, methods diagnosis or monitoring, drug target discovery, vaccine generation, basic definition pathophysiological processes biochemical mechanisms behind spread SARS-CoV-2. Thus, term COVIDomics wants include those efforts provided by omics-scale investigations with current research. This review summarizes diverse pieces knowledge acquired techniques, main focus proteomics metabolomics studies, in order capture common signature terms proteins, metabolites, pathways dysregulated disease. Exploring multiomics perspective concurrent data integration may provide new suitable therapeutic solutions combat pandemic.

Language: Английский

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Metabolomics in the Diagnosis and Prognosis of COVID-19

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: July 23, 2021

Coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented global effort in developing rapid and inexpensive diagnostic prognostic tools. Since the genome of SARS-CoV-2 was uncovered, detection viral RNA by RT-qPCR has played most significant role preventing spread virus through early tracing suspected COVID-19 cases screening at-risk population. However, a large number alternative test methods based on or proteins host factors associated with infection have been developed evaluated. The application metabolomics infectious diagnostics is evolving area science that boosted urgency pandemic. Metabolomics approaches rely analysis volatile organic compounds exhaled patients hold promise for applications large-scale population point-of-care (POC) setting. On other hand, successful mass-spectrometry to detect specific spectral signatures nasopharyngeal swab specimens may significantly save cost turnaround time testing microbiology virology laboratories. Active research also ongoing discovery potential metabolomics-based markers can be applied serum plasma specimens. Several metabolic pathways related amino acid, lipid energy metabolism were found affected severe COVID-19. In particular, tryptophan via kynurenine pathway persistently dysregulated several independent studies, suggesting roles metabolites this such as tryptophan, 3-hydroxykynurenine disease. standardization clinical validation are necessary before these tests With rapidly expanding data profiles varying degrees severity, it likely will play important near future predicting outcome greater degree certainty.

Language: Английский

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Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

Metabolism, Journal Year: 2022, Volume and Issue: 131, P. 155197 - 155197

Published: April 2, 2022

Language: Английский

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Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 15, 2023

COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at respiratory track, it is clear that pathophysiology has a systemic ultimately affecting many organs. This feature enables possibility investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or nuclear magnetic resonance (NMR) spectroscopy. Here we review extensive literature on metabolomics in COVID-19, unraveled aspects disease including: characteristic metabotipic signature associated discrimination patients according severity, effect drugs and vaccination treatments characterization natural history metabolic evolution disease, from full recovery long-term long sequelae COVID.

Language: Английский

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Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101254 - 101254

Published: Oct. 26, 2023

The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during 6 months following their acute phase infection to comprehensively profile assess changes in cytokines, proteome, metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, cellular activation convalescence accompanied by dysregulation arginine biosynthesis, methionine metabolism, taurine tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed 20 molecules involved regulating T cell exhaustion energy metabolism that can reliably predict clinical outcomes discharge 83% accuracy an area under the curve (AUC) 0.96. Our study pertinent biological processes differ infection, it supports development specific therapies biomarkers for patients suffering COVID.

Language: Английский

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Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 5, 2023

Severe COVID-19 is characterized by an increase in the number and changes function of innate immune cells including neutrophils. However, it not known how metabolome patients with COVID-19. To address these questions, we analyzed neutrophils from severe or mild healthy controls. We identified widespread dysregulation neutrophil metabolism disease progression amino acid, redox, central carbon metabolism. Metabolic were consistent reduced activity glycolytic enzyme GAPDH. Inhibition GAPDH blocked glycolysis promoted pentose phosphate pathway but blunted respiratory burst. was sufficient to cause extracellular trap (NET) formation which required elastase activity. inhibition increased pH, blocking this prevented cell death NET formation. These findings indicate that have aberrant can contribute their dysfunction. Our work also shows formation, a pathogenic feature many inflammatory diseases, actively suppressed cell-intrinsic mechanism controlled

Language: Английский

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Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 9, 2023

Background Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity clinical symptoms potential biomarkers for disease 2019 (COVID-19). Several studies described the role small as well complex molecules such metabolites, cytokines, chemokines lipoproteins during in recovered patients. In fact, after SARS-CoV-2 viral almost 10-20% experience persistent post 12 weeks recovery defined long-term COVID-19 (LTCS) or long post-acute (PACS). Emerging evidence revealed that dysregulated immune system persisting inflammation could be one key drivers LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, clear understanding parameters within integrated fashion predict course would help to stratify LTCS This even allow elucidation mechanistic course. Methods study comprised subjects (n=7; longitudinal), (n=33), Recov (n=12), no history positive testing (n=73). 1 H-NMR-based metabolomics IVDr standard operating procedures verified phenotyped all blood samples by quantifying 38 metabolites 112 lipoprotein properties. Univariate multivariate statistics identified NMR-based cytokine changes. Results Here, we report on analysis serum/plasma NMR spectroscopy flow cytometry-based cytokines/chemokines quantification We lactate pyruvate were significantly different either healthy controls (HC) Subsequently, correlation group only among cytokines amino acids histidine glutamine uniquely attributed mainly pro-inflammatory cytokines. Of note, triglycerides several (apolipoproteins Apo-A1 A2) demonstrate COVID-19-like alterations compared HC. Interestingly, distinguished mostly their phenylalanine, 3-hydroxybutyrate (3-HB) glucose concentrations, illustrating imbalanced energy metabolism. Most present at low levels HC except IL-18 chemokine, which tended higher Conclusion The identification plasma will better other diseases ongoing severity

Language: Английский

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