Comparative metabolomic analysis reveals shared and unique features of COVID-19 cytokine storm and surgical sepsis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 24, 2025

The clinical manifestations of the cytokine storm (CS) associated with COVID-19 resemble acute phase sepsis. Metabolomics may contribute to understanding specific pathobiology these two syndromes. aim this study was compare serum metabolomic profiles in CS vs. septic surgery patients. In a retrospective cross-sectional study, samples from patients COVID-19, and without comorbidity, as well surgical sepsis were investigated. Targeted analysis performed on all using LC–MS/MS. Analysis revealed that similar alterations metabolome amino acid metabolism, nitrogen inflammatory status, methionine cycle glycolysis. most significant difference found for levels metabolites kynurenine synthesis, tricarboxylic cycle, gamma-aminobutyric niacinamide. metabolic pathway cysteine metabolism significantly disturbed For first time, similarities differences between investigated Northwest Russian Federation.

Language: Английский

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Exercise-induced adaptations in the kynurenine pathway: implications for health and disease management

Frontiers in Sports and Active Living, Journal Year: 2025, Volume and Issue: 7

Published: March 6, 2025

Background Tryptophan (TRP) metabolism through the kynurenine (KYN) pathway is influenced by inflammatory mediators, generating metabolites that regulate immune and responses. Exercise has been proposed as a modulator of this pathway, but its role in health benefits chronic disease management remains unclear. Objective This systematic review examines exercise-induced adaptations KYN their potential implications for management. Additionally, we identify key methodological considerations future research. Methods A structured search PubMed/Medline, Web Science, Scopus was conducted up to October 2024 clinical trials investigating effects exercise training on pathway. Results Of 2,795 articles initially found, 13 involving 592 participants met inclusion criteria. Most studies reported particularly cancer survivors. These appeared be intensity duration. However, several limitations were noted, no included patients with metabolic or cardiovascular diseases. Conclusions Here, show modulates both healthy diseased populations, highlighting prevention further randomized-controlled are needed clarify mechanisms applications, Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022351481 , PROSPERO (CRD42022351481).

Language: Английский

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Predisposing and Precipitating Factors in Epstein–Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 702 - 702

Published: March 21, 2025

Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification risk factors predisposing patients to developing maintaining post-infectious syndromes may help uncover their underlying mechanisms. majority with ME/CFS report illnesses before the onset ME/CFS, 30% cases due IM caused by Epstein–Barr virus. After IM, one study found 11% adults had at 6 months 9% 1 year. Another adolescents 13% 7% 12 respectively. However, it is unclear which variables potential contributing development maintenance because few prospective studies have collected baseline data triggering illness. current article provides an overview a that included pre-illness predictors in diverse group college students who were enrolled IM. Our set ethnically sociodemographically young adult students, we able longitudinally follow these youths over time better understand associated pathophysiology ME/CFS. General screens health psychological well-being, as well blood samples, obtained three stages (Stage 1—Baseline—when well, least weeks student developed IM; Stage 2—within diagnosis 3—six after when they either or recovered). We focused on for new both 1) 2) predicted nonrecovery. now collecting seven-year follow-up this sample, including long COVID. lessons learned reviewed.

Language: Английский

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1, 8-Cineole Ameliorated Staphylococcus aureus-Induced Pneumonia through Modulation of TRP-KYN and Arginine-NO Reprogramming

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

1, 8-Cineole (Cin), a cyclic monoterpenoid derived from tea trees and eucalyptus species, exhibits diverse pharmacological properties. Yet, its therapeutic impact underlying mechanism against Staphylococcus aureus (S. aureus) pneumonia remain to be elucidated. In this study, metabolomics based on UPLC-MS/MS was integrated with network pharmacology, molecular biology, docking investigate the effects of Cin. The findings demonstrated that Cin markedly reduced mortality lung bacterial load, lessened pulmonary damage while suppressing levels proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) infected mice. Additionally, 19 metabolites, primarily involved tryptophan metabolism arginine biosynthesis, were notably modified by via enzymatic activity indoleamine 2, 3-dioxygenase 1 (IDO1) inducible nitric oxide synthase (iNOS), thereby attenuating inflammatory response. Notably, knockdown IDO1 or iNOS significantly diminished anti-inflammation effect conclusion, our study validates potential S. downregulating iNOS. Our results provide theoretical basis natural substances applied treatment.

Language: Английский

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Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(5), P. e1013164 - e1013164

Published: May 19, 2025

Viruses modulate various aspects of host physiology, including carbon metabolism, redox balance, and mitochondrial bioenergetics to acquire the building blocks for replication regulation immune response. Understanding how SARS-CoV-2 alters metabolism may lead treatments COVID-19. We report that a ubiquitous gaseous molecule, hydrogen sulfide (H 2 S), regulates redox, control SARS-CoV-2. Virus is associated with down-regulation H S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (3-MST) in multiple cell lines nasopharyngeal swabs symptomatic COVID-19 patients. Consequently, SARS-CoV-2-infected cells showed diminished endogenous S levels protein modification (S-sulfhydration) caused by S. Genetic silencing or chemical inhibition CTH resulted proliferation. Chemical supplementation using slow-releasing donor, GYY4137, virus replication. Using biosensor, metabolomics, transcriptomics, XF-flux analyzer, we GYY4137 blocked inducing Nrf2/Keap1 pathway, restoring balance metabolites potentiating oxidative phosphorylation. Treatment mice hamsters suppressed viral ameliorated lung pathology. treatment reduced expression inflammatory cytokines re-established Nrf2-dependent antioxidant genes lungs mice. Notably, non-invasive measurement respiratory functions unrestrained whole-body plethysmography (uWBP) improved pulmonary function variables, obstruction (Penh), end-expiratory pause (EEP), relaxation time (RT) upon treatment. Together, our findings significantly extend understanding S-mediated infections open new avenues investigating pathogenic mechanisms therapeutic opportunities coronavirus-associated disorders.

Language: Английский

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Exploring metabolic anomalies in COVID-19 and post-COVID-19: a machine learning approach with explainable artificial intelligence

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 9, 2024

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant challenges worldwide, including diverse clinical outcomes and prolonged post-recovery symptoms known as Long COVID or Post-COVID-19 syndrome. Emerging evidence suggests a crucial role of metabolic reprogramming in the infection's long-term consequences. This study employs novel approach utilizing machine learning (ML) explainable artificial intelligence (XAI) analyze alterations patients. Samples were taken from cohort 142 COVID-19, 48 Post-COVID-19, 38 control patients, comprising 111 identified metabolites. Traditional analysis methods, like PCA PLS-DA, compared with ML techniques, particularly eXtreme Gradient Boosting (XGBoost) enhanced SHAP (SHapley Additive exPlanations) values for explainability. XGBoost, combined SHAP, outperformed traditional demonstrating superior predictive performance providing new insights into basis disease's progression aftermath. revealed metabolomic subgroups within conditions, suggesting heterogeneous responses infection its impacts. Key signatures include taurine, glutamine, alpha-Ketoglutaric acid, LysoPC C16:0. highlights potential integrating XAI fine-grained description metabolomics research, offering more detailed understanding anomalies conditions.

Language: Английский

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Modifications in Immune Response Patterns Induced by Kynurenine and One-Residue-Substituted T Cell Epitopes in SARS-CoV-2-Specific Human T Cells

COVID, Journal Year: 2024, Volume and Issue: 4(10), P. 1676 - 1683

Published: Oct. 15, 2024

Peptide p176-190, derived from the SARS-CoV-2 spike protein, is one of major T cell epitopes that elicits HLA-DR-restricted IL-8 response human CD4+ cells. Using PBMCs a healthy individual primed with an S-protein-based vaccine, we established line (TM45) and cloned cells (TM45.2) specific for peptide. We showed (i) co-incubation kynurenine leads to increased IL-8; (ii) incubated in absence recovered original levels cytokine production; (iii) peptide p176-190 substituted at 176 Leucine neutral hydrophilic serine completely abolished responses TM45.2 cells, thereby suggesting L first anchor residue binding HLA-DR. These observations collectively indicate enhanced can be induced by kynurenine, which produced under infectious conditions COVID-19; not permanent change phenotype; associated harmful neutrophil extracellular traps abrogated single amino acid substitution viral antigens. findings may shed light on novel strategy designing vaccines infections are accompanied production.

Language: Английский

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Post-Coronavirus Disease 2019 Effects in an Active University Population: A Within-Campus Cross-Sectional Study at a Major Educational Institution

Mayo Clinic Proceedings Innovations Quality & Outcomes, Journal Year: 2024, Volume and Issue: 8(6), P. 521 - 529

Published: Nov. 12, 2024

Language: Английский

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High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship elucidate the underlying biological pathways. included 59 participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Sass spectrometry (LC-HRMS), weighted Quantile Sum (WQS) regression applied assess PFAS effects on IgG. Metabolite indices positively or negatively were constructed separately their mediation examined independently jointly. The PFAS-index (beta=-0.273, p=0.002), PFHpS PFHxS as major contributors. Two metabolite-indices constructed, one (beta=1.260, p<0.001) (beta=-0.997, Key contributors for these protoporphyrin, 5-hydroxytryptophan, n-acetylproline, tyrosine. Analysis of single mediator showed 48.9% (95%CI: 21.9%,125.0%) 50.1% (95% CI: 8.1%, 90.1%) index-IgG total effect mediated by negative positive metabolite-indices, respectively. Joint analysis indicated cumulative 73.6% 44.9%, 116.4%). Enriched pathways phenylalanine, tyrosine, tryptophan biosynthesis arginine metabolism. observed significant plasma PFAS-IgG relationship, suggesting disrupts balance contributes reduced production.

Language: Английский

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