SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7910 - 7910

Published: April 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Language: Английский

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JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Nov. 8, 2023

Abstract The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological pathological processes such inflammation stress. Dysregulation this can lead to severe immunodeficiencies malignancies, its role extends neurotransduction pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological inflammatory disorders, their application has generally been limited diseases with similar pathogenic features. Despite the modest expression of JAK-STAT CNS, it is crucial for functions cortex, hippocampus, cerebellum, making relevant conditions like Parkinson's disease other neuroinflammatory disorders. Furthermore, influence on serotonin receptors phospholipase C implications stress mood This review expands understanding JAK-STAT, moving beyond traditional contexts explore stress-related disorders CNS function. Recent findings, effectiveness Jakinibs chronic rheumatoid arthritis, expand therapeutic applicability. Advances isoform-specific inhibitors, including filgotinib upadacitinib, promise greater specificity fewer off-target effects. Combination therapies, involving monoclonal antibodies, aiming enhance efficacy also give great hope. Overall, bridges gap between basic science clinical application, elucidating complex human health guiding future interventions. Graphical

Language: Английский

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Inflammation: A New Look at an Old Problem

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4596 - 4596

Published: April 21, 2022

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It defined by a number universal components, including oxidative stress, cellular response DNA damage, unfolded protein mitochondrial and endoplasmic reticulum changes autophagy, inflammasome formation, non-coding RNA response, formation an inducible network signaling pathways, epigenetic changes. The presence receptor secretory phenotype many the cause tissue pro-inflammatory stress. key phenomenon determining occurrence classical inflammatory focus microvascular (exudation, leukocyte migration alteration zone). This same reaction at systemic level leads development life-critical inflammation. From this standpoint, we can characterize common mechanisms pathologies differ their clinical appearance. division inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects also described review. aim review provide theoretical arguments for need up-to-date theory relationship between human pathological processes based on integrative role molecular

Language: Английский

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Urinalysis, but Not Blood Biochemistry, Detects the Early Renal Impairment in Patients with COVID-19

Diagnostics, Journal Year: 2022, Volume and Issue: 12(3), P. 602 - 602

Published: Feb. 27, 2022

Background: Coronavirus 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has created a tremendous economic and medical burden. The prevalence prognostic value of SARS-CoV-2-induced kidney impairment remain controversial. current study aimed to provide additional evidence on incidence injury (AKI) in COVID-19 patients propose use urinalysis as tool for screening impairment. Methods: 178 with confirmed were enrolled this retrospective cohort study. laboratory examinations included routine blood tests, biochemical analyses (liver function, renal lipids, glucose), coagulation index, lymphocyte subset cytokine analysis, urine test, C-reactive protein, erythrocyte sedimentation, serum ferritin. Results: No patient exhibited rise creatinine or Cystatin C occurrence AKI, only 2.8% recorded an elevated level urea nitrogen among all cases. On contrary, 54.2% who underwent testing presented abnormal featured proteinuria, hematuria, leucocyturia. Conclusions: Kidney is prevalent patients, clinical manifestation, implying that test stronger indication prospective complication than biochemistry test.

Language: Английский

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Endothelial dysfunction, platelet hyperactivity, hypertension, and the metabolic syndrome: molecular insights and combating strategies

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 8, 2023

Metabolic syndrome (MetS) is a multifaceted condition that increases the possibility of developing atherosclerotic cardiovascular disease. MetS includes obesity, hypertension, dyslipidemia, hyperglycemia, endothelial dysfunction, and platelet hyperactivity. There concerning rise in occurrence frequency globally. The rising incidence severity need proactive, multipronged strategy for identifying treating those affected. For many patients, achieving recommended goals healthy fat intake, blood pressure control, glucose management may require combination medicine therapy, lifestyles, nutraceuticals, others. However, it essential to note lifestyle modification should be first-line therapy MetS. In addition, requires pharmacological, nutraceutical, or other interventions. This review aimed bring together etiology, molecular mechanisms, dietary strategies combat dysfunction individuals with

Language: Английский

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Acute and Chronic Systemic Inflammation: Features and Differences in the Pathogenesis, and Integral Criteria for Verification and Differentiation

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1144 - 1144

Published: Jan. 6, 2023

Currently, there is rationale for separating the systemic manifestations of classical inflammation from (SI) itself as an independent form general pathological process underlying pathogenesis most severe acute and chronic diseases. With this aim in view, we used integral scales SI (ChSI), including following blood plasma parameters: interleukins 6, 8, 10; tumor necrosis factor alpha; C-reactive protein; D-dimer; cortisol; troponin I; myoglobin. The presence multiple organ dysfunction according to SOFA score was also taken into account. effectiveness tested groups intensive care patients during different periods trauma, sepsis, septic shock. ChSI scale applicable under autoimmune diseases, purulent infections, limb threatening ischemia, end-stage renal disease various genesis. number examined 764 total. allowed us verify specific phases identify pathogenetic risk factors lethal outcomes, well variants pathologies course. These are open adaptable systems (in terms nomenclature choice indicators). They primarily intended scientific research. However, verification methodology presented paper may be useful developing advanced criteria assessing both typical links many diseases severity overall condition clinical practice.

Language: Английский

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The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11453 - 11453

Published: Oct. 23, 2021

Chronic kidney disease can progress to end-stage chronic renal (ESRD), which requires the use of replacement therapy (dialysis or transplant) in life-threatening conditions. In ESRD, irreversible changes kidneys are associated with systemic proinflammatory nature and dysfunctions internal organs, skeletal muscles, integumentary tissues. The common components ESRD pathogenesis, regardless initial nosology, (1) local (in kidneys) low-grade inflammation (ChLGI) as a risk factor for diabetic its progression (2) classical type characteristic primary secondary autoimmune glomerulonephritis infectious recurrent pyelonephritis, well immune reactions allograft rejection, (3) (ChSI), pathogenetically characterized by latent microcirculatory disorders manifestations paracoagulation. development ChSI is closely programmed hemodialysis process. Consideration pathogenesis from standpoint theory general pathological processes opens up scope not only particular but also universal approaches conducting pathogenetic therapies diagnosing predicting complications severe nephropathies.

Language: Английский

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Theophylline: Old Drug in a New Light, Application in COVID-19 through Computational Studies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4167 - 4167

Published: April 9, 2022

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged development effective pharmacological treatments directly attack new variants SARS-CoV-2 virus and possess therapeutical battery compounds that could improve current management disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, potentially antiviral mechanisms, an interesting proposal as adjuvant treatment patients. Nevertheless, it essential understand how compound behave against such disease, not only at pharmacodynamic but also pharmacokinetic level. sense, quickest approach discovery different computational methods, either from network pharmacology quantitative systems approaches. present review, we explore possibility using theophylline patients since seems be relevant candidate by aiming several immunological targets involved pathophysiology disease. down-regulates inflammatory processes activated various herein, they are discussed reviewing simulation studies their applications effects.

Language: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 816 - 816

Published: May 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Language: Английский

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