Oxidative Stress and Lung Fibrosis: Towards an Adverse Outcome Pathway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12490 - 12490

Published: Aug. 6, 2023

Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives fibrotic changes. Persistent injury due to oxidative stress and chronic inflammation are central features fibrosis. Chronic cigarette smoking causes major risk factor for The objective this manuscript develop an adverse outcome pathway (AOP) that serves as framework investigation the mechanisms caused by inhaled toxicants, including smoke. Based on weight evidence, proposed molecular initiating event (MIE) leads increased secretion proinflammatory profibrotic mediators (key 1 (KE1)). At cellular level, these signals induce recruitment inflammatory (KE2), turn, increase fibroblast proliferation myofibroblast differentiation (KE3). tissue extracellular matrix deposition (KE4) subsequently culminates fibrosis, outcome. We have also defined new KE relationship between MIE KE3. This AOP provides mechanistic platform understand evaluate how persistent from may into

Language: Английский

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Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review

International Journal of Environmental Research and Public Health, Journal Year: 2024, Volume and Issue: 21(4), P. 473 - 473

Published: April 12, 2024

Introduction: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There emerging evidence of different pathophysiological mechanisms driving the wide array symptoms in LC. Understanding relationships between and helps guiding clinical management identifying potential treatment targets. Methods: This was mixed-methods systematic review with two stages: Stage one (Review 1) included only existing reviews (meta-review) 2) all primary studies. The search strategy involved Medline, Embase, Emcare, CINAHL databases to identify studies that described statistical analysis and/or discussion plausible causal symptoms. Only control arm for comparison were included. Studies assessed quality using National Heart, Lung, Blood Institute assessment tools. Results: 19 Review 1 46 2. Overall, reporting across this second moderate poor. strong immune system dysregulation, cerebral hypoperfusion, impaired gas transfer lungs. Other weak endothelial damage hypercoagulation, mast cell activation, auto-immunity vascular receptors. Conclusions: LC complex condition multiple organs diverse presentations (or traits) underpinned by mechanisms. A ‘treatable trait’ approach may help certain groups target specific interventions. Future research must include understanding response intervention based on these mechanism-based traits.

Language: Английский

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Pulmonary fibrosis: A short- or long-term sequelae of severe COVID-19?

Chinese Medical Journal - Pulmonary and Critical Care Medicine, Journal Year: 2023, Volume and Issue: 1(2), P. 77 - 83

Published: Jan. 23, 2023

The pandemic of coronavirus disease 2019 (COVID‑19), caused by a novel severe acute respiratory syndrome (SARS) 2 (SARS-CoV-2), has an enormous impact on the global healthcare. SARS-CoV-2 infection primarily targets system. Although most individuals testing positive for present mild or no upper tract symptoms, patients with COVID-19 can rapidly progress to distress (ARDS). ARDS-related pulmonary fibrosis is recognized sequelae COVID-19. Whether post-COVID-19 lung resolvable, persistent, even becomes progressive as seen in human idiopathic (IPF) currently not known and remains matter debate. With emergence effective vaccines treatments against COVID-19, it now important build our understanding long-term sequela infection, identify survivors who are at risk developing chronic fibrosis, develop anti-fibrotic therapies. current review aims summarize pathogenesis system highlights potential mechanisms. It envisions fibrotic complication survivors, particular aged population. early identification development therapies discussed.

Language: Английский

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Adipokines as Diagnostic and Prognostic Markers for the Severity of COVID-19

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1302 - 1302

Published: April 27, 2023

Accumulating evidence implicates obesity as a risk factor for increased severity of disease outcomes in patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Obesity is associated adipose tissue dysfunction, which not only predisposes individuals to metabolic complications, but also substantially contributes low-grade systemic inflammation, altered immune cell composition, and compromised function. This seems impact the susceptibility outcome diseases caused by viruses, obese people appear more vulnerable developing infections they recover later from infectious than normal-weight individuals. Based on these findings, efforts identify suitable diagnostic prognostic markers Coronavirus 2019 (COVID-19) predict have been made. includes analysis cytokines secreted tissues (adipokines), multiple regulatory functions body; instance, modulating insulin sensitivity, blood pressure, lipid metabolism, appetite, fertility. Most relevant context viral infections, adipokines influence number, consequences overall activity Hence, circulating levels diverse SARS-CoV-2 considered reveal COVID-19 markers. review article summarizes findings aimed correlate progression COVID-19. Several studies provided insights chemerin, adiponectin, leptin, resistin, galectin-3 SARS-CoV-2-infected patients, while limited information yet available apelin visfatin Altogether, current points at resistin being value disease.

Language: Английский

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Molecular mechanisms of COVID-19-induced pulmonary fibrosis and epithelial-mesenchymal transition

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

Published: Aug. 3, 2023

As the outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Hubei Province, China, at end 2019. It has brought great challenges and harms to global public health. SARS-CoV-2 mainly affects lungs is manifested as pulmonary disease. However, one biggest crises arises from emergence COVID-19-induced fibrosis. At present, there are still many questions about how induced fibrosis (PF) occurs treat regulate its long-term effects. In addition, an important process fibrosis, effect on epithelial-mesenchymal transition (EMT) may be factor driving PF. This review summarizes main pathogenesis treatment mechanisms related Starting with basic PF, such EMT, transforming growth factor-β (TGF-β), fibroblasts myofibroblasts, inflammation, macrophages, innate lymphoid cells, matrix metalloproteinases tissue inhibitors metalloproteinases, hedgehog pathway well Notch signaling. Further, we highlight importance EMT PF provide overview molecular mechanisms, which will facilitate future research propose new clinical therapeutic solutions for

Language: Английский

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Pharmacological approaches to pulmonary fibrosis following COVID-19

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

Published: June 15, 2023

In the past few years, COVID-19 became leading cause of morbidity and mortality worldwide. Although World Health Organization has declared an end to as a public health emergency, it can be expected, that emerging new cases at top previous ones will result in increasing number patients with post-COVID-19 sequelae. Despite fact majority recover, severe acute lung tissue injury susceptible individuals progress interstitial pulmonary involvement. Our goal is provide overview various aspects associated Post-COVID-19 fibrosis focus on its potential pharmacological treatment options.

Language: Английский

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Altered serum concentrations of IL-8, IL-32 and IL-10 in patients with lung impairment 6 months after COVID-19

Immunobiology, Journal Year: 2024, Volume and Issue: 229(4), P. 152813 - 152813

Published: May 24, 2024

Post-COVID symptoms are reported in 10–35 % of patients not requiring hospitalization, and up to 80 hospitalized with severe disease. The pathogenesis post-COVID syndrome remains largely unknown. Some evidence suggests that prolonged inflammation has a key role the most manifestations. We evaluated panel inflammatory immune-mediated cytokines individuals altered HRCT features without any long-term COVID symptoms. Blood samples 89 adult previously COVID-19 were collected stratified as fibrotic lung alterations. Serum analyte concentrations IL-4, IL-2, CXCL10 (IP-10), IL-1β, TNF-α, CCL2 (MCP-1), IL-17A, IL-6, IL-10, IFN-γ, IL-12p70 TGF-β1 (free active form) quantified by bead-based multiplex assay. Clinical functional data recorded database. With use machine learning approach, IL-32, IL-8, IL-10 proved be associated development sequelae at follow-up. Direct comparison cytokine levels two groups showed increased IL-32 decreased IL-8 impairment. After further stratification severity (severe versus mild/moderate) during emerged only showing patients. These findings contribute better understanding immune response potential prognostic markers after COVID-19.

Language: Английский

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SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling

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

Published: July 20, 2023

SARS-CoV-2, the cause of COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated A549 cells expressing individual ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). is a member IL6 family cytokines. signaling-related genes also differentially expressed. Bioinformatics disclosed involved pulmonary fibrosis idiopathic disease functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison lung lines infected biopsies patients COVID-19, evidenced altered gene expression matched those obtained study. Our results show involvement inflammatory Thus, these could be targeted by new therapies against disease.

Language: Английский

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Autophagy in Inflammatory Response against SARS-CoV-2

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4928 - 4928

Published: March 3, 2023

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused 500 million cumulative cases, claimed lives of 6.4 people worldwide as August 2022. causative agent severe acute respiratory syndrome 2 (SARS-CoV-2). Depicting this virus’ life cycle pathogenic mechanisms, well cellular host factors pathways involved during infection, great relevance for development therapeutic strategies. Autophagy a catabolic process that sequesters damaged cell organelles, proteins, external invading microbes, delivers them to lysosomes degradation. would be entry, endo, release, transcription translation, viral particles cell. Secretory autophagy also developing thrombotic immune-inflammatory seen significant number COVID-19 patients can lead illness even death. This review aims main aspects characterize complex not yet fully elucidated relationship between SARS-CoV-2 infection autophagy. It briefly describes key concepts regarding mentions its pro- antiviral roles, while noting reciprocal effect autophagic their clinical aspects.

Language: Английский

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COVID-19: A threat to the respiratory system

International Journal of Immunopathology and Pharmacology, Journal Year: 2024, Volume and Issue: 38

Published: Jan. 1, 2024

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes coronavirus disease-19 (COVID-19) that has emerged on a pandemic level. Coronaviruses are well-known to have negative impact the lungs and cardiovascular system. SARS-CoV-2 induces cytokine storm primarily targets lungs, causing widespread clinical disorders, including COVID-19. Although, positive individuals often show no or mild upper tract symptoms, cases can progress distress (ARDS). Novel CoV-2 infection in 2019 resulted viral pneumonia as well other complications extrapulmonary manifestation. ARDS is also linked higher risk of death. Now, it essential develop our perception long term sequelae for identification COVID-19 survivors who at developing chronic lung fibrosis. This review study was planned provide an overview effects various parts system such airways, pulmonary vascular, parenchymal neuromuscular potential mechanism related fibrosis patients with

Language: Английский

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