Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes DOI Creative Commons
Victòria Ceperuelo‐Mallafré, Laia Reverté,

Joaquim Peraire

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 14, 2022

Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, can disrupt extracellular signalling. We hypothesized that examining energy-related signalling metabolites implicated SARS-CoV-2 infection would provide potential biomarkers for predicting risk COVID-19 illness. used a semi-targeted serum metabolomics approach 273 patients with different severity grades recruited at phase determine relative abundance tricarboxylic acid (Krebs) cycle-related known signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels were evaluated validation cohort (n=398) using quantitative fluorimetric assays. Increased four a-ketoglutarate succinate) found critically ill targeted approaches (p<0.05). The combined strategy proposed herein enabled us establish circulating pyruvate (p<0.001) together body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer creatinine (p=0.043) levels, are independent predictors critical COVID-19. Furthermore, classification regression tree (CART) analysis provided cut-off value (24.54 µM; p<0.001) as early criterion accurately classify outcomes. Our findings support link between pathogenesis immunometabolic dysregulation, show fluorometric quantification cost-effective clinical decision tool improve patient stratification prognosis prediction.

Language: Английский

Associations between TCA cycle plasma metabolites and fatigue in black females with systemic lupus erythematosus: An untargeted metabolomics pilot study DOI
Laura P. Kimble, Arezou Khosroshahi, Glenna Brewster

et al.

Lupus, Journal Year: 2024, Volume and Issue: 33(9), P. 948 - 961

Published: June 17, 2024

Objective In this pilot study, we used untargeted metabolomics to identify biochemical mechanisms or biomarkers potentially underlying SLE-related fatigue. Methods Metabolon conducted metabolomic plasma profiling using ultrahigh performance liquid chromatography/tandem mass spectrometry on samples of 23 Black females with systemic lupus erythematosus (SLE) and 21 no SLE controls. Fatigue phenotypes general fatigue, physical mental reduced activity, motivation were measured the reliable valid Multidimensional Inventory (MFI). Results A total 290 metabolites significantly different between groups, encompassing related glycolysis, TCA cycle heme catabolism, branched chain amino acids, fatty acid metabolism, steroids. Within group, controlling for age co-morbidities, alpha-ketoglutarate (AKG) succinate statistically associated ( p < .05) Conclusion While pervasive perturbations in entire have been implicated as a potential mechanism our results suggest individual AKG may be targets intervention fatigue symptom management SLE. Additionally, metabolism group provide additional insights into that promote inflammation.

Language: Английский

Citations

3
Structural insights into ligand recognition and activation of the succinate receptor SUCNR1 DOI Creative Commons
Aijun Liu,

Yezhou Liu,

Weijia Zhang

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114381 - 114381

Published: June 25, 2024

Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as stress signal through receptor (SUCNR1), class A G protein-coupled receptor. Research on signaling is hampered by the lack of high-resolution structures agonist-bound We present cryoelectron microscopy (cryo-EM) SUCNR1-Gi complexes bound to its non-metabolite derivative cis-epoxysuccinate. Key determinants for recognition cis conformation include R2817.39 Y832.64, while Y301.39 R993.29 participate binding both loop 2, F175ECL2 β-hairpin, forms hydrogen bond with caps pocket. At receptor-Gi interface, agonist induces rearrangement hydrophobic network transmembrane (TM)5 TM6, leading TM TM3 TM7. These findings extend our understanding SUCNR1, aiding development therapeutics

Language: Английский

Citations

3
The role of microbial succinate in the pathophysiology of inflammatory bowel disease: mechanisms and therapeutic potential DOI
Sonia Fernández‐Veledo, Carme Grau‐Bové, Sara Notararigo

et al.

Current Opinion in Microbiology, Journal Year: 2025, Volume and Issue: 85, P. 102599 - 102599

Published: March 25, 2025

Language: Английский

Citations

0
Gut Microbiome—Brain Crosstalk in the Early Life of Chicken Reveals the Circadian Regulation of Key Metabolic and Immune Signaling Processes DOI Creative Commons
Mridula Gupta,

Mustafa Cilkiz,

Mohamed M. Ibrahim

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 789 - 789

Published: March 30, 2025

Circadian rhythms are innate biological systems that control everyday behavior and physiology. Furthermore, bilateral interaction between the host’s circadian rhythm gut microbes influences a variety of health ramifications, including metabolic diseases, obesity, mental GALT physiology microbiome population. Therefore, we studying correlation differential gene expression in chicken brain microbiota abundance during rhythms. To understand this, raised freshly hatched chicks under two photoperiod treatments: normal (NP = 12/12 LD) extended (EP 23/1 LD). The were randomly assigned to one treatments. After 21 days entrainment, euthanized at nine time points spaced six hours apart over 48 h characterize transcriptomes. Each sample’s RNA was extracted, 36 mRNA libraries generated sequenced using Illumina technology, followed by data processing, count generation, analysis. We an average 17.5 million reads per library for 237.9 M reads. When aligned Galgal6 reference genome, 11,867 genes had detectable levels, with common dispersion value 0.105. identify follow 24 rhythms, counts performed DiscoRhythm. discovered 577 Cosinor 417 JTK cycle algorithm exhibit substantial used weighted co-expression network analysis (WGCNA) analyze differentially expressed abundance. most enriched pathways included aldosterone-regulated sodium reabsorption, endocrine other factor-regulated calcium GABAergic synapse, oxidative phosphorylation, serotonergic dopaminergic synapse entrainment. This study builds on our previous study, adds new findings about specific interactions co-regulation transcriptome microbiota. host highlights potential benefits microbiome-modulation approaches improve performance poultry.

Language: Английский

Citations

0
Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes DOI Creative Commons
Victòria Ceperuelo‐Mallafré, Laia Reverté,

Joaquim Peraire

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 14, 2022

Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, can disrupt extracellular signalling. We hypothesized that examining energy-related signalling metabolites implicated SARS-CoV-2 infection would provide potential biomarkers for predicting risk COVID-19 illness. used a semi-targeted serum metabolomics approach 273 patients with different severity grades recruited at phase determine relative abundance tricarboxylic acid (Krebs) cycle-related known signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels were evaluated validation cohort (n=398) using quantitative fluorimetric assays. Increased four a-ketoglutarate succinate) found critically ill targeted approaches (p<0.05). The combined strategy proposed herein enabled us establish circulating pyruvate (p<0.001) together body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer creatinine (p=0.043) levels, are independent predictors critical COVID-19. Furthermore, classification regression tree (CART) analysis provided cut-off value (24.54 µM; p<0.001) as early criterion accurately classify outcomes. Our findings support link between pathogenesis immunometabolic dysregulation, show fluorometric quantification cost-effective clinical decision tool improve patient stratification prognosis prediction.

Language: Английский

Citations

16