Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 1, 2022

Many local and systemic diseases especially that are leading causes of death globally like chronic obstructive pulmonary disease, atherosclerosis with ischemic heart disease stroke, cancer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing 19 (COVID-19), involve both, (1) oxidative stress excessive production reactive oxygen species (ROS) lower glutathione (GSH) levels, (2) inflammation. The GSH tripeptide (γ- L-glutamyl-L-cysteinyl-glycine), the most abundant water-soluble non-protein thiol in cell (1–10 mM) is fundamental for life by (a) sustaining adequate redox signaling needed to maintain physiologic levels control processes, (b) limiting tissue damage. activity facilitated activation Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related (Nrf2)-antioxidant response element (ARE) regulator pathway, releasing Nrf2 regulates expression genes controlling antioxidant, inflammatory immune system responses. exists thiol-reduced (>98% total GSH) disulfide-oxidized (GSSG) forms, concentrations GSSG their molar ratio indicators functionality cell. depletion may play a central role COVID-19 pathophysiology, host severity mortality. Therapies enhancing could become cornerstone reduce fatal outcomes increasing prevent subdue these diseases. value makes paramount research field biology medicine be key against inflammation SARS-CoV-2 infection disease. In this review, we emphasize on as risk (ischemic stroke), importance antioxidants (3) significance counteract persistent damaging inflammation, inflammaging early (premature) associated damage caused lack antioxidant defenses younger individuals, (4) new therapies include restoration.

Language: Английский

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Immune responses in mildly versus critically ill COVID-19 patients

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

Published: Jan. 30, 2023

The current coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has had devastating effects on the global health and economic system. cellular molecular mediators of both innate adaptive immune systems are critical in controlling SARS-CoV-2 infections. However, dysregulated inflammatory responses imbalanced immunity may contribute to tissue destruction pathogenesis disease. Important mechanisms severe forms COVID-19 include overproduction cytokines, impairment type I IFN response, overactivation neutrophils macrophages, decreased frequencies DC cells, NK cells ILCs, complement activation, lymphopenia, Th1 Treg hypoactivation, Th2 Th17 hyperactivation, as well clonal diversity B lymphocyte function. Given relationship between disease severity an system, scientists have been led manipulate system a therapeutic approach. For example, anti-cytokine, cell, IVIG therapies received attention treatment COVID-19. In this review, role development progression is discussed, focusing aspects mild vs. Moreover, some immune- based approaches being investigated. Understanding key processes involved developing agents optimizing related strategies.

Language: Английский

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SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(3)

Published: April 6, 2023

The antioxidant defense system plays a major function in protecting the organism against oxidative damage caused by free radicals. COVID-19 patients often present with biochemical characteristics of uncontrolled pro-oxidative responses respiratory tract.

Language: Английский

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"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review

Balkan Medical Journal, Journal Year: 2024, Volume and Issue: unknown, P. 7 - 22

Published: Jan. 3, 2024

Heartfailure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia pulmonary stroke, Takotsubo venous thromboembolism, and thrombocytopenia.In this narrative review, we describe elucidate when, where, how COVID-19 affects the human cardiovascular system in various parts of body that are vulnerable every patient category, including children athletes.

Language: Английский

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Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

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

Published: Oct. 6, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes disease 19 (COVID-19) has numerous risk factors leading to severe with high mortality rate. Oxidative stress excessive production of reactive oxygen species (ROS) lower glutathione (GSH) levels seems be a common pathway associated the COVID-19 mortality. GSH is unique small but powerful molecule paramount for life. It sustains adequate redox cell signaling since physiologic level oxidative fundamental controlling life processes via signaling, oxidation and tissue damage. The water-soluble tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) present in cytoplasm all cells. at 1–10 mM concentrations mammalian tissues (highest concentration liver) as most abundant non-protein thiol protects against stress. also activates Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related (Nrf2)-antioxidant response element (ARE) regulator pathway, releasing Nrf2 regulate expression genes control antioxidant, inflammatory immune system responses, facilitating activity. exists thiol-reduced disulfide-oxidized (GSSG) forms. Reduced prevailing form accounting >98% total GSH. GSSG their molar ratio are indicators functionality its alteration related various human pathological including COVID-19. plays prominent role SARS-CoV-2 infection following recognition viral S-protein by angiotensin converting enzyme-2 receptor pattern receptors like toll-like 4, activation transcription nuclear kappa B, subsequently activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) succeeded ROS production. depletion may have pathophysiology, host severity Therapies enhancing could become cornerstone reduce fatal outcomes increasing prevent subdue disease. value makes research field biology medicine key

Language: Английский

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COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 15, 2024

Abstract Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated more severe outcomes among patients living haematological disorders and malignancies (HDMs). Because individuals moderate immunodeficiency are likely undergo persistent infections, shed virus particles for prolonged periods, lack an inflammatory or abortive phase, this represents overall risk of morbidity mortality from COVID-19. In cases suffering HDMs, further investigation is needed achieve a better understanding triviruses group related variants anemia as well their treatment through vaccines, drugs, other methods. Against background, the present study aimed delineate relationship between HDMs novel COVID-19, acute respiratory syndrome 2 (SARS-CoV-2). Besides, effective options HDM were explored address epidemic its variants. Therefore, learning about how COVID-19 manifests these patients, along exploiting most appropriate treatments, lead development care strategies by clinicians researchers help recover faster.

Language: Английский

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Long-Term Risk of Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

JAMA Dermatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Importance Few studies have investigated the association between COVID-19 and autoimmune autoinflammatory connective tissue disorders; however, research with long-term observation remains insufficient. Objective To investigate risk of diseases after over an extended period. Design, Setting, Participants This retrospective nationwide population-based study Korea Disease Control Prevention Agency–COVID-19–National Health Insurance Service (K-COV-N) cohort. Individuals confirmed from October 8, 2020, to December 31, 2022, controls identified among individuals who participated in general health examination 2018 were included analysis. Exposures Confirmed COVID-19. Main Outcomes Measures Incidence disorders patients Various covariates, such as demographic characteristics, data, socioeconomic status, comorbidity profiles, balanced using inverse probability weighting. Results A total 6 912 427 participants (53.6% male; mean [SD] age, 53.39 [20.13] years) consisting 3 145 388 767 039 observational period more than 180 days included. Alopecia areata (adjusted hazard ratio [AHR], 1.11 [95% CI, 1.07-1.15]), alopecia totalis (AHR, 1.24 1.09-1.42]), vitiligo 1.04-1.19]), Behçet disease 1.45 1.20-1.74]), Crohn 1.35 1.14-1.60]), ulcerative colitis 1.15 1.04-1.28]), rheumatoid arthritis 1.09 1.06-1.12]), systemic lupus erythematosus 1.14 1.01-1.28]), Sjögren syndrome 1.13 1.03-1.25]), ankylosing spondylitis 1.02-1.20]), bullous pemphigoid 1.62 1.07-2.45]) associated higher group. Subgroup analyses revealed that factors, including male female sex, age younger 40 years, years older, exhibited diverse associations outcomes. In addition, severe infection requiring intensive care unit admission, Delta period, not being vaccinated risk. Conclusions Relevance cohort follow-up found various disorders. Long-term monitoring is crucial COVID-19, considering severity, vaccination mitigate these risks.

Language: Английский

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Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10344 - 10344

Published: Sept. 7, 2022

SARS-CoV-2 is a new coronavirus characterized by high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases cytokines compromise their survival. Soluble factors are clinically pathologically relevant in COVID-19 survival but remain only partially characterized. The objective this work was to simultaneously study 62 circulating soluble factors, including innate adaptive receptors, chemokines growth wound-healing/repair severe who survived compared those with fatal outcomes. Serum samples were obtained from 286 40 healthy controls. quantified using Luminex Milliplex assay. Results. had decreased levels the following 30 studied outcomes, therefore, these decreases observed for receptors predominantly produced system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI sTNF-RII—for IL-8, IP-10, MCP-1, MCP-3, MIG fractalkine; M-CSF receptor sIL2Ra; involved system IFNγ, IL-17 sIL-4R; wound-repair factor FGF2. On other hand, elevated TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA PDGFABBB died. Conclusions. Increases sCD40L cytokine; MDC RANTES chemokines; G-CSF GM-CSF PDGFABBB; tissue-repair strongly associated By contrast, large increases IL-27 IL-10; sIL-1RI, sIL1RII sTNF-RII receptors; MCP3, IP-10 sIL-2Ra factors; wound-healing FGF2 favor outcomes disease.

Language: Английский

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Autoantibodies - enemies, and/or potential allies?

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

Published: Oct. 19, 2022

Autoantibodies are well known as potentially highly harmful antibodies which attack the host via binding to self-antigens, thus causing severe associated diseases and symptoms (e.g. autoimmune diseases). However, detection of autoantibodies a range disease-associated antigens has enabled their successful usage important tools in disease diagnosis, prognosis treatment. There several advantages using such autoantibodies. These include capacity measure presence very early development, stability, is often much better than related antigen, use an array for enhanced diagnostics predict prognosis. They may also possess utilization therapy, vivo . In this review both positive negative aspects critically assessed, including role diseases, cancers global pandemic caused by COVID-19. Important issues highlighted.

Language: Английский

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Diabetic endothelial microangiopathy and pulmonary dysfunction

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

Published: March 21, 2023

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by macrovascular microvascular bed degradation brought on metabolic, hemodynamic, inflammatory variables. However, research in recent years has expanded target organ T2DM to include lung. Inflammatory lung diseases also impose severe financial burden healthcare. long been recognized as significant comorbidity influences course of various respiratory disorders their disease progress. The pathogenesis glycemic problem endothelial microangiopathy have garnered more attention lately, indicating two ailments shared history. This review aims outline connection between related cell dysfunction concomitant diseases, including Coronavirus 2019 (COVID-19), asthma, chronic obstructive pulmonary (COPD) idiopathic fibrosis (IPF).

Language: Английский

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