Sex/gender-related differences in inflammaging

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 211, P. 111792 - 111792

Published: Feb. 17, 2023

Geroscience puts mechanisms of aging as a driver the most common age-related diseases and dysfunctions. Under this perspective, addressing basic will produce better understanding than each disease pathophysiology individually. Worldwide, despite greater functional impairment, life expectancy is higher in women men. Gender differences prevalence multimorbidity lead mandatory to underlying gender-related patterns disability-free expectancy. Extensive literature suggested that inflammaging at crossroad diseases. In review, we highlight main evidence on sex/gender foster inflammaging, i.e. age-dependent triggering innate immunity, modifications adaptive accrual senescent cells, underpinning some biomarkers show sex-related differences. framework "gender medicine perspective", also discuss how can affect sex COVID-19 severe outcomes.

Language: Английский

---

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

---

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

---

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 1, 2024

Abstract The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression inflammatory responses associate with alterations in microbiome metabolome, we analyzed metagenome, cytokine, transcriptome profiles repeated samples from hospitalized patients uninfected controls, leveraged information post-hoc confounder analysis. Severe was associated a depletion beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance mainly linked to antibiotic use. severity also enhanced plasma concentrations kynurenine reduced levels several other tryptophan metabolites, lysophosphatidylcholines, secondary bile acids. Moreover, various metabolites were Faecalibacterium , decrease increase production cytokines. Collectively, our study identifies correlated metabolome as potential contributor dysregulation severe COVID-19.

Language: Английский

---

The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9082 - 9082

Published: Aug. 21, 2024

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters receptors display micromolar binding constants; these are consistent with its typically tissue concentrations but far above serum/plasma concentration (normally tens nanomolar), suggesting large gaps in our knowledge transport mechanisms action, the main influx characterized date equilibrative, not concentrative. In addition, it substrate known anion efflux pump (ABCC4), whose vivo activity largely unknown. Exogeneous addition L-tryptophan or L-kynurenine leads production KYNA also many other co-metabolites (including some such as 3-hydroxy-L-kynurenine quinolinic may be toxic). With exception chestnut honey, exists at relatively low levels natural foodstuffs. bioavailability reasonable, terminal element irreversible reaction most pathways, might added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show valuable bioactivity. Given above, review potential utility nutraceutical, finding significantly worthy further study development.

Language: Английский

---

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

---

Metabolomic characteristics and related pathways in patients with different severity of COVID-19: a systematic review and meta-analysis

Journal of Global Health, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 28, 2025

Despite advances in metabolomic research on COVID-19, existing studies have small sample sizes and few comprehensively described the metabolic characteristics of patients with COVID-19 at each stage. In this systematic review, we aimed to summarise similarities differences biomarkers different severity describe their stages. We retrieved from PubMed, Embase, Web Science, Cochrane Library published by October 2022. performed a meta-analysis untargeted targeted metabolomics data, using ratio means as effect size. compared changes metabolite levels between varying controls investigated sources heterogeneity through subgroup analyses meta-regression analysis. included 22 cohorts 21 studies, comprising 2421 participants, including healthy controls. conducted analysis 1058 metabolites study. The results indicated that, control group, 23 were associated mild cases (P < 0.05), 3 moderate 37 severe 0.05). Pathway enrichment revealed significant disturbances amino acid metabolism, aminoacyl-tRNA biosynthesis, primary bile pantothenate CoA tricarboxylic cycle, taurine hypotaurine nitrogen metabolism mild, moderate, disease. Additionally, found that stage exhibited unique patterns (all P 0.05) degree dysregulation progressively worsened increasing disease our indicate thereby providing new pathways for study pathogenesis, development precise treatment, formulation comprehensive strategies. PROSPERO: CRD42022369937.

Language: Английский

---

Pasteur effect in leukocyte energy metabolism of patients with mild, moderate, and severe COVID-19

Turkish Journal of Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Abstract Objectives The Pasteur effect in cellular energy metabolism is defined as the switch to anaerobic glycolysis due alterations ambient oxygen concentration or inhibition of electron transport chain (ETC) and oxidative phosphorylation. This study aimed determine Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on leukocytes among Disease 2019 (COVID-19) patients at various stages. Methods A total 90 cases were analyzed asymptomatic, mild, moderate, severe COVID-19 patients. Levels aerobic intermediates products measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results decrease rate was found disease progressed (p-values<0.001), while unchanged all groups because lactate levels had no difference between (p=0.754). Moreover, ratios Tricarboxylic Acid (TCA) cycle parameters demonstrated a significant reduction different stages (p-values<0.001). Furthermore, Receiver Operating Characteristic (ROC) curve analysis for citrate, alpha-ketoglutarate, fumarate, lactate, lactate/citrate, lactate/alpha-ketoglutarate, lactate/fumarate cut-off values Moderate (p<0.001). Conclusions Our results suggest that from shown be induced severity progresses.

Language: Английский

---

Integrative Metabolomic and Lipidomic Signatures of SARS-CoV-2 VOCs: Correlations with Hematological and Biochemical Markers

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

In the present study, we investigated biochemical, hematological, lipidomic, and metabolomic alterations associated with different SAR-CoV-2 variants of concern (VOCs), such as WT, α, β, γ, δ, well their impact on COVID-19 severity. Across first second waves in India, a machine learning approach was used 3134 patients, nine critical biochemical hematological parameters, namely, C-reactive protein (CRP), D-dimer, ferritin, neutrophil, WBC count, lymphocyte, urea, creatine, lactate dehydrogenase (LDH), were identified. Furthermore, through metabolic lipidomic profiles lung colon cells transfected spike VOCs, notable dysregulation exhibited by delta variant correlated characteristic pathways catecholamine thyroid hormone synthesis. A corroborating meta-analysis also highlighted involvement urea amino acid metabolism pathways. Overall, our study provides crucial insights into disruptions caused contributing to better understanding pathogenesis development targeted interventions.

Language: Английский

---

Clinical and Genetic Analysis of Patients With TK2 Deficiency

Neurology Genetics, Journal Year: 2024, Volume and Issue: 10(2)

Published: March 25, 2024

Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring depletion. Subsequently, less severe variants disease were described, onset symptoms during adolescence or adulthood and presence multiple mtDNA deletions. These phenotypes have been reported only 15% approximately 120 patients described worldwide. However, some reports suggest these juvenile adult-onset presentations may be more common. The objective this study to describe clinical phenotype sample Spain.

Language: Английский

---