Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102957 - 102957

Published: Nov. 3, 2023

Progressive respiratory failure is the primary cause of death in coronavirus disease 2019 (COVID-19) pandemic. It final outcome acute distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance cellular energy may result crucial for recovery clinical COVID-19. Hence, we asked if two key pathways involved generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling fatty acid oxidation (FAO) could be beneficial. We tested drugs metformin (AMPK activator) baicalin (CPT1A different experimental models mimicking COVID-19 associated inflammation lung kidney. also studied cohorts patients that had been previously treated with metformin. These ameliorated damage ARDS animal model, while activation AMPK/ACC increased mitochondrial function decreased TGF-β-induced fibrosis, apoptosis markers epithelial cells. Similar results were observed indole derivatives, IND6 IND8 AMPK activating capacity. Consistently, a reduced time hospitalization need intensive care was exposed to Baicalin mitigated pro-inflammatory bone marrow-derived macrophages (BMDMs) kidney fibrosis injury, another target In human cells, both improved prevented renal cell dedifferentiation. Our support favoring production through enhanced FAO prove useful prevention COVID-19-induced damage.

Language: Английский

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Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: Feb. 27, 2024

Abstract Rationale Acute respiratory distress syndrome (ARDS) is a life-threatening critical care commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, potential interventions reduce inflammation promote lung repair. Objective To map compare metabolic phenotypes different infectious causes ARDS better understand the pathways involved in underlying pathogenesis. Methods We analyzed 3 cohorts caused by H1N1 pneumonia compared non-ARDS COVID-19-infected patients ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from total 150 using quantitative LC–MS/MS DI-MS/MS analytical platforms. Results Distinct were detected between ARDS. There differences ARDSs COVID-19 H1N1, which include involving taurine hypotaurine, pyruvate, TCA cycle metabolites, lysine, glycerophospholipids. differed metabolism D-glutamine D-glutamate, arginine, proline, histidine, pyruvate. The profile (C19/A) admitted ICU (C19/P) who not metabolisms phenylalanine, tryptophan, tyrosine. Metabolomics analysis revealed significant C19/A, H1N1/A, PNA/A vs controls, reflecting potentially disease mechanisms. Conclusion Different characterize viral infections.

Language: Английский

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Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients

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

Published: Nov. 20, 2022

Abstract Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation disease progression. We performed metabolomic 30 and 19 controls using high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC–MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism biosynthesis aminoacyl-tRNAs, which differed significantly between controls. Using ANDSystem software, reconstruction gene networks describing potential genetic regulation perturbed by SARS-CoV-2 proteins. The nonstructural proteins (orf8 nsp5) structural protein E were involved greater number regulatory pathways. reconstructed suggest hypotheses on molecular mechanisms virus-host interactions pathology provide basis further experimental computer studies Our suggests need protein-based vaccines control strategy to reduce progression COVID-19.

Language: Английский

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MBROLE3: improved functional enrichment of chemical compounds for metabolomics data analysis

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(W1), P. W305 - W309

Published: May 13, 2023

Abstract MBROLE (Metabolites Biological Role) facilitates the biological interpretation of metabolomics experiments. It performs enrichment analysis a set chemical compounds through statistical annotations from several databases. The original server was released in 2011 and, since then, different groups worldwide have used it to analyze experiments variety organisms. Here we present latest version system, MBROLE3, accessible at http://csbg.cnb.csic.es/mbrole3. This new contains updated previously included databases as well wide functional annotations, such additional pathway and Gene Ontology terms. Of special relevance is inclusion category ‘indirect annotations’, extracted scientific literature curated chemical-protein associations. latter allows enriched proteins known interact with interest. Results are provided form interactive tables, formatted data download, graphical plots.

Language: Английский

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MetaboliteCOVID: A manually curated database of metabolite markers for COVID-19

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 167, P. 107661 - 107661

Published: Nov. 1, 2023

Language: Английский

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Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 985 - 985

Published: June 19, 2024

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients.

Language: Английский

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Persistence of Metabolomic Changes in Patients during Post-COVID Phase: A Prospective, Observational Study

Metabolites, Journal Year: 2022, Volume and Issue: 12(7), P. 641 - 641

Published: July 13, 2022

Several relatively recently published studies have shown changes in plasma metabolites various viral diseases such as Zika, Dengue, RSV or SARS-CoV-1. The aim of this study was to analyze the metabolome profile patients during acute COVID-19 approximately one month after infection and compare these results with healthy (SARS-CoV-2-negative) controls. analysis performed by NMR spectroscopy from peripheral blood samples were collected on 3 different occasions (at admission, hospitalization control visit discharge hospital). When comparing sample groups (based date acquisition) controls, there is an indicative shift metabolomics features based time passed first taken towards Based random forest algorithm, a strong discriminatory predictive value between controls (AUC equals 1 for versus at Mathew correlation coefficient 1). Significant metabolomic persist more than SARS-CoV-2 infection. algorithm shows very discrimination (almost ideal) when metabolite levels two stages disease recovery period compared SARS-CoV-2-negative

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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Cross-Validation of Metabolic Phenotypes in SARS-CoV-2 Infected Subpopulations Using Targeted Liquid Chromatography–Mass Spectrometry (LC-MS)

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(4), P. 1313 - 1327

Published: March 14, 2024

To ensure biological validity in metabolic phenotyping, findings must be replicated independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile validate phenotypes SARS-CoV-2 infection. Two sets were collected: (1) Australia: plasma, positive (n = 20), noninfected healthy controls 22) COVID-19 disease-like symptoms but negative infection 22). (2) Spain: serum, 33) 39). Multivariate modeling using orthogonal projections latent structures discriminant analyses (OPLS-DA) classified from (Australia; R2 0.17, ROC-AUC 1; Spain 0.20, 1). Univariate revealed 23 significantly different (p < 0.05) metabolites between individuals across both cohorts. Significant consistent perturbations cellular energy metabolism (pyruvic acid, 2-oxoglutaric acid), oxidative stress (lactic 2-hydroxybutyric hypoxia (2-hydroxyglutaric 5-aminolevulinic liver activity (primary acids), host-gut microbial cometabolism (hippuric phenylpropionic indole-3-propionic acid). These data support targeted LC-MS phenotyping

Language: Английский

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Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in MAFLD and COVID-19 Outcomes

Published: May 13, 2024

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients. Methods: We investigated levels AHR, FFAR2, FXR, TGR5 patients with compared to controls. examined associations between clinical outcomes. Results: displayed altered AHR expression, potentially impacting recovery. Downregulated correlated increased coagulation parameters. Elevated FFAR2 linked specific cell populations hospital stay duration. Significantly lower FXR was observed both Conclusion: Our findings suggest modulatory roles MAFLD.

Language: Английский

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