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 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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Integrative Plasma Metabolic and Lipidomic Modelling of SARS-CoV-2 Infection in Relation to Clinical Severity and Early Mortality Prediction

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11614 - 11614

Published: July 18, 2023

An integrative multi-modal metabolic phenotyping model was developed to assess the systemic plasma sequelae of SARS-CoV-2 (rRT-PCR positive) induced COVID-19 disease in patients with different respiratory severity levels. Plasma samples from 306 unvaccinated were collected 2020 and classified into four levels ranging mild symptoms severe ventilated cases. These investigated using a combination quantitative Nuclear Magnetic Resonance (NMR) spectroscopy Mass Spectrometry (MS) platforms give broad lipoprotein, lipidomic amino acid, tryptophan-kynurenine pathway, biogenic amine pathway coverage. All revealed highly significant differences metabolite patterns between controls (n = 89) that had been prior pandemic. The total number metabolites increased 344 out 1034 variables being common all classes. Metabolic signatures showed continuum changes across most extensive severely affected patients. Even mildly multiple abnormal biochemical reflecting serious deficiencies type observed Post-acute syndrome high mortality (56.1%) we found could predict this patient sub-group accuracy some cases up 61 days death, based on separate model, which highlighted set those defining basic disease. Specifically, hexosylceramides (HCER 16:0, HCER 20:0, 24:1, 26:0, 26:1) markedly elevated non-surviving group (Cliff's delta 0.91-0.95) two phosphoethanolamines (PE.O 18:0/18:1, Cliff's -0.98 PE.P 16:0/18:1, -0.93) lower non-survivors. results indicate morbidity trajectories is determined relatively soon after infection, opening opportunity select more intensive therapeutic interventions these "high risk" early stages.

Language: Английский

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Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 110110 - 110110

Published: May 25, 2024

Increased cases of sepsis during COVID-19 in the absence known bacterial pathogens highlighted role viruses as causative agents sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics viral patients (

Language: Английский

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Serum nuclear magnetic resonance metabolomics analysis of human metastatic colorectal cancer: Biomarkers and pathway analysis

NMR in Biomedicine, Journal Year: 2023, Volume and Issue: 36(9)

Published: March 22, 2023

We describe the use of nuclear magnetic resonance metabolomics to analyze blood serum samples from healthy individuals (n = 26) and those with metastatic colorectal cancer (CRC; n 57). The assessment, employing both linear nonlinear multivariate data analysis techniques, revealed specific metabolite changes associated CRC, including increased levels lactate, glutamate, pyruvate, decreased certain amino acids total fatty acids. Biomarker ratios such as glutamate-to-glutamine pyruvate-to-alanine were also found be related CRC. study that glutamate was linked progression-free survival 3-hydroxybutyrate risk factors for Additionally, gas chromatography coupled flame-ionization detection utilized acid profile pathway performed on profiled metabolites understand metabolic processes involved in A correlation between presence CRC patients clinical features.

Language: Английский

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Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7593 - 7593

Published: April 20, 2023

The coronavirus disease 2019 (COVID-19) pandemic has caused the death of almost 7 million people worldwide. While vaccinations and new antiviral drugs have greatly reduced number COVID-19 cases, there remains a need for additional therapeutic strategies to combat this deadly disease. Accumulating clinical data discovered deficiency circulating glutamine in patients with that associates severity. Glutamine is semi-essential amino acid metabolized plethora metabolites serve as central modulators immune endothelial cell function. A majority glutamate ammonia by mitochondrial enzyme glutaminase (GLS). Notably, GLS activity upregulated COVID-19, favoring catabolism glutamine. This disturbance metabolism may provoke dysfunction contributes development severe infection, inflammation, oxidative stress, vasospasm, coagulopathy, which leads vascular occlusion, multi-organ failure, death. Strategies restore plasma concentration glutamine, its metabolites, and/or downstream effectors, conjunction drugs, represent promising approach function prevent occlusive stricken COVID-19.

Language: Английский

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Epigenetic patterns, accelerated biological aging, and enhanced epigenetic drift detected 6 months following COVID-19 infection: insights from a genome-wide DNA methylation study

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 20, 2024

The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. existence long-COVID, or post-acute sequelae SARS-CoV-2 (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless initial severity. mechanisms behind long-COVID are unclear, but virus-induced changes could play a role. Our study explores the lasting impacts infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort 96 6 months after COVID-19 exposure, comparing them to 191 healthy controls. identified 42 CpG sites with significant differences (FDR < 0.05), primarily within islands gene promoters. Dysregulated genes highlighted links glutamate/glutamine metabolism, which may be relevant PASC symptoms. Key significance effects include GLUD1, ATP1A3, ARRB2. Furthermore, Horvath's clock showed slight age acceleration patients. also observed substantial increase stochastic mutations (SEMs) group, implying drift. SEM analysis 790 affected genes, indicating dysregulation pathways related insulin resistance, VEGF signaling, apoptosis, hypoxia response, T-cell activation, endothelin signaling. provides valuable insights into consequences COVID-19. Results suggest possible associations accelerated aging, drift, disruption critical biological linked immune vascular health. Understanding these crucial for elucidating complex developing targeted therapeutic interventions.

Language: Английский

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Host specific sphingomyelin is critical for replication of diverse RNA viruses

Cell chemical biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

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

Published: Aug. 16, 2023

Background COVID-19 could develop severe respiratory symptoms in certain infected patients, especially the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators human body contribute to responses impacting progression of COVID-19. However, causal relationship between specific intestinal bacteria, metabolites remains not clear. Methods Based on two-sample Mendelian randomization (MR) framework, effects 131 taxa 452 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated abundance concentration had been utilized as instrument variables infer whether they factors In addition, mediation analysis was conducted find potential association taxon metabolite, further colocalization performed validate relationships. Results MR identified 13 53 metabolites, which significantly factors. Mediation revealed 11 mediated Myo-inositol, 2-stearoylglycerophosphocholine, alpha-glutamyltyrosine, potentially contributed Howardella Ruminiclostridium 6 COVID-19, respectively. Butyrivibrio Ruminococcus gnavus mediate myo-inositol N-acetylalanine, torques colocalized (PP.H4 = 0.77) colon expression permeability related protein RASIP1 0.95). Conclusions Our study highlights relationships gut microbiome, serve clinical biomarkers for risk stratification prognostication benefit mechanism mechanistic investigation

Language: Английский

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Untargeted plasma metabolome identifies biomarkers in patients with extracranial arteriovenous malformations

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

Published: Sept. 1, 2023

Objective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed analyze profiles both groups. Metabolic pathway enrichment analysis performed through Kyoto Encyclopedia Genes Genomes (KEGG) database MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage Selection Operator (LASSO) random forest (RF) conducted screen characteristic metabolites. The effectiveness serum biomarkers for evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites screened in this study, 110 positive ion mode 74 negative mode. Lipids lipid-like molecules predominant detected modes. Several significant pathways enriched AVMs, including lipid metabolism, amino acid carbohydrate protein translation. Through algorithms, nine identify metabolites, hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic dihydrojasmonic acid. Conclusion: Patients AVMs exhibited significantly altered patterns compared controls, which could be identified metabolomics. These findings suggest that metabolomic profiling can aid understanding pathophysiology potentially inform clinical diagnosis treatment.

Language: Английский

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