The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis

Antioxidants, Год журнала: 2023, Номер 12(11), С. 1942 - 1942

Опубликована: Окт. 31, 2023

Zinc is a structural component of proteins, functions as catalytic co-factor in DNA synthesis and transcription hundreds enzymes, has regulatory role protein-DNA interactions zinc-finger proteins. For many years, zinc been acknowledged for its anti-oxidative anti-inflammatory functions. Furthermore, potent inhibitor caspases-3, -7, -8, modulating the caspase-controlled apoptosis necroptosis. In recent immunomodulatory sepsis COVID-19 investigated. Both are related to various regulated cell death (RCD) pathways, including Lack may have negative effect on immune functions, such oxidative burst, cytokine production, chemotaxis, degranulation, phagocytosis, RCD. While plasma concentrations decline swiftly during both COVID-19, this reduction primarily attributed redistribution process associated with inflammatory response. response, hepatic metallothionein production increases reaction release, which linked inflammation, protein effectively captures stores liver. Multiple mechanisms come into play, influencing uptake zinc, binding blood albumin red cells, well buffering modulation cytosolic levels. Decreased levels increasing severity organ dysfunction, prolonged hospital stay increased mortality septic patients. Results studies focusing these topics summarized discussed narrative review. Existing evidence currently does not support pharmacological supplementation patients or COVID-19. Complementation repletion should follow current guidelines micronutrients critically ill Further research investigating mechanism programmed caused by invasive infections therapeutic potential could be worthwhile.

Язык: Английский

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Ferroptosis: a novel mechanism of cell death in ophthalmic conditions

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 27, 2024

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation differs from death, such as apoptosis, necrosis, autophagy. Ferroptosis associated with variety physiological pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence development diseases targeting metabolic pathways signaling tumors, ischemic organ damage, other degenerative related to peroxidation. Increasing evidence suggests closely linked onset progression various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, retinoblastoma. Our review current research on reveals significant advancements our understanding pathogenesis, aetiology, treatment these conditions.

Язык: Английский

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Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Фев. 19, 2024

The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling nuclear factor kappa light chain enhancer in B-cells (NF-κB)-driven interleukin (IL)-1β, IL-6, IL-18 secretion causing cytokine storms. translation the how resulting systemic inflammation can lead life-threatening complications into novel treatments vaccine technologies is underway. Nevertheless, previously existing role cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported ‘ de novo ’ for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 be outcomes self-DNA-driven fact had been linked earlier different contexts, e.g., infection Human Immunodeficiency Virus (HIV)-1, sterile inflammation, autoimmune diseases. highlight particularly synergies other DAMPs render immunogenic properties normally non-immunogenic extracellular self-DNA, discuss shared features gp41 unit HIV-1 envelope protein SARS-CoV 2 Spike that enable SARS-CoV-2 interact cell membranes, trigger syncytia formation, inflict damage their host’s DNA, – likely own benefit. These similarities motivate speculations similar mechanisms those driven by explain inflammatory contributes some most frequent adverse events after vaccination BNT162b2 mRNA (Pfizer/BioNTech) mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, nephritis hepatitis, new-onset lupus erythematosus, flare-ups psoriasis lupus. hope wider application lessons learned from experiences COVID-19 new vaccines combat future non-COVID-19

Язык: Английский

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Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(8), С. 167472 - 167472

Опубликована: Авг. 20, 2024

Язык: Английский

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Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach

Viruses, Год журнала: 2025, Номер 17(3), С. 359 - 359

Опубликована: Фев. 28, 2025

This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 patients (40 survivors 40 non-survivors) with pneumonia acute respiratory failure. The median time the onset symptoms hospital was lower non-survivors than (p < 0.05). Respiratory failure, expressed as ratio arterial oxygen partial pressure fraction inspired (P/F), more severe 0.0001). Comorbidities were similar both groups. Among parameters cytokines, eGFR interleukin (IL)-1β found be significantly 0.05), while LDH, IL-10, IL-8 higher 0.0005, p 0.05 0.005, respectively). other LDH values distribution showed most significant difference between groups LASSO feature selection combined Cox proportional hazards logistic regression models applied features distinguishing non-survivors. Both approaches highlighted strongest predictor, IL-22 creatinine emerging model, eGFR, influential model (AUC = 0.744 for Cox, 0.723 regression). In a manner, we linear predicting levels, identifying P/F top followed by IL-10 (NRMSE 0.128). Collectively, these findings underscore LDH’s critical role prediction, key determinants increases this Italian cohort.

Язык: Английский

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Interleukin-6 regulates human ODAM gene expression in gingival epithelial cells

Journal of Periodontal & Implant Science, Год журнала: 2025, Номер 55

Опубликована: Янв. 1, 2025

Odontogenic ameloblast-associated protein (ODAM) is a small secretory produced by the junctional epithelium (JE) and mature ameloblasts. It plays role in odontogenesis mediates adhesion of JE to enamel. We used human gingival epithelial cells evaluate mechanism ODAM gene expression regulation interleukin (IL)-6. Ca9-22, Sa3, HSY were stimulated with IL-6 (10 ng/mL), after which total RNA proteins extracted. Real-time polymerase chain reaction Western blot analyses performed assess levels mRNA protein. Luciferase (LUC) assays employed using LUC constructs varying lengths promoter sequence. Gel mobility shift chromatin immunoprecipitation (ChIP) conducted investigate binding transcription factors response elements within promoter. Treatment increased expressions Additionally, it induced activity gene, while was suppressed inhibitors kinase A, tyrosine kinase, MEK1/2, phosphatidylinositol 3-kinase, nuclear factor-κB, signal transducer activator (STAT) 3, glycoprotein 130. ChIP revealed that yin yang 1 (YY1), CCAAT/enhancer-binding (C/EBP) β, GATA (GATA), phospho-STAT3 YY1, C/EBP, GATA, interferon-γ activated transcriptional element (GATE) 1-3 elements. These findings indicate upregulates targeting GATE1-3 region gene.

Язык: Английский

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COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 21, 2024

Introduction Although many studies have underscored the importance of T cells, phenotypically and functionally, fewer studied functions myeloid cells in COVID disease. In particular, potential role such as monocytes low-density neutrophils (LDNs) innate responses particular defense against secondary bacterial infections has been much less documented. Methods Here, we compared, a longitudinal study, healthy subjects, idiopathic fibrosis patients, patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) hospitalized for other reasons (non-COV-ICU). Results We show that an increased proportion (LDNs), which produce high levels proteases (particularly, NE, MMP-8 MMP-9) (unlike non-COV-ICU patients), are partly responsible causing type II alveolar cell damage co-culture experiments. addition, showed M- ICU-COVID had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, important pathogen colonizing ICU, assessed by impaired secretion cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid (in 2/type 3) remained high, both basally post PAO1 reflected unimpaired capacity proliferate, when stimulated with anti-CD3/CD28 beads. Discussion Overall, our results demonstrate circulatory biased 2/3 phenotype, unconducive proper anti-viral dual deleterious through their LDN-mediated damaging effect on (monocyte-mediated) pathogens P. .

Язык: Английский

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Rhei Radix et Rhizoma in Xuanbai-Chengqi decoction strengthens the intestinal barrier function and promotes lung barrier repair in preventing severe viral pneumonia induced by influenza A virus

Journal of Ethnopharmacology, Год журнала: 2023, Номер 319, С. 117231 - 117231

Опубликована: Сен. 30, 2023

Язык: Английский

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Building an Adverse Outcome Pathway network for COVID-19

Frontiers in Systems Biology, Год журнала: 2024, Номер 4

Опубликована: Июнь 7, 2024

The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing vast knowledge in succinct manner. Between April 2020 and February 2023, CIAO consortium exploited Adverse Outcome Pathway (AOP) framework comprehensively gather systematically organize published scientific literature pathology. project considered 24 pathways relevant by identifying essential key events (KEs) 19 adverse outcomes observed patients. While an individual AOP defines causally linked perturbed KEs towards outcome, building network visually reflect interrelatedness various outcomes. In this study, 17 those AOPs were selected based quality criteria computationally derive network. This primary highlighted consider tissue specificity helped identify missing or redundant elements which then manually implemented final Such enabled visualization complex interactions multifaceted confirmed central role inflammatory response disease. addition, study disclosed importance terminology harmonization tissue/organ building. Furthermore unequal completeness information contained tighter implementation FAIR principles improve findability, accessibility, interoperability re-usability. Finally, underlined that describing specific SARS-CoV-2 replication discriminating physiological from pathological inflammation is necessary but requires adaptations framework. Hence, challenges encountered, we proposed recommendations ongoing future AOP-aligned consortia aiming build biologically meaningful networks context of, not limited to, viral diseases.

Язык: Английский

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Early inflammatory profiles predict maximal disease severity in COVID-19: An unsupervised cluster analysis

Heliyon, Год журнала: 2024, Номер 10(15), С. e34694 - e34694

Опубликована: Июль 23, 2024

The inflammatory changes that underlie the heterogeneous presentations of COVID-19 remain incompletely understood. In this study we aimed to identify profiles precede development severe COVID-19, could serve as targets for optimised delivery immunomodulatory therapies and provide insights new therapies.

Язык: Английский

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