Angiotensin‐converting enzyme 2 (ACE2), SARS‐CoV‐2 and the pathophysiology of coronavirus disease 2019 (COVID‐19)

The Journal of Pathology, Journal Year: 2020, Volume and Issue: 251(3), P. 228 - 248

Published: May 17, 2020

Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2), virus responsible current devastating worldwide pandemic of disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety cells residing many different human organs. In physiology, pivotal counter-regulatory to ACE by breakdown angiotensin II, central player renin-angiotensin-aldosterone system (RAAS) and main substrate ACE2. Many factors have associated with both altered expression COVID-19 severity progression, including age, sex, ethnicity, medication, several co-morbidities, such cardiovascular metabolic syndrome. Although widely distributed various tissues its determinants well recognised, ACE2-expressing organs do not equally participate pathophysiology, implying that other mechanisms are involved orchestrating cellular infection resulting tissue damage. Reports pathologic findings specimens patients rapidly emerging confirm role activity pathogenesis. Identifying changes caused SARS-CoV-2 crucially important it major implications understanding pathophysiology development evidence-based treatment strategies. Currently, interventional strategies being explored ongoing clinical trials, encompassing drug classes strategies, antiviral drugs, biological response modifiers, RAAS inhibitors. Ultimately, prevention key combat appropriate measures taken accordingly, effective vaccines. this review, we describe influencing relation severity. addition, discuss relevant pathological from infection. Finally, highlight selection potential modalities COVID-19. © 2020 The Authors. Journal Pathology published John Wiley & Sons Ltd on behalf Pathological Society Great Britain Ireland.

Language: Английский

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Oxidative Stress, Plant Natural Antioxidants, and Obesity

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1786 - 1786

Published: Feb. 11, 2021

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors mitochondrial activity, modifying concentration inflammation mediators associated with a large number and size adipocytes, promoting lipogenesis, stimulating differentiation preadipocytes to mature regulating energy balance hypothalamic neurons that control appetite. This review discusses participation oxidative obesity groups compounds found plants antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, isoflavones), curcuminoids (b) carotenoids, (c) capsaicinoids casinoids, (d) isothiocyanates, (e) catechins, (f) vitamins. Examples are analyzed, resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, garlic. The activities these depend on their reactive oxygen species (ROS) scavengers capacity prevent activation NF-κB (nuclear factor κ-light-chain-enhancer activated B cells), reduce expression target genes, including those participating inflammation. We conclude natural have therapeutic potential for diseases mediated by stress, particularly obesity. Controlled well-designed clinical trials still necessary better know effects compounds.

Language: Английский

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Resveratrol and Vascular Function

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(9), P. 2155 - 2155

Published: April 30, 2019

Resveratrol increases the production of nitric oxide (NO) in endothelial cells by upregulating expression NO synthase (eNOS), stimulating eNOS enzymatic activity, and preventing uncoupling. At same time, resveratrol inhibits synthesis endothelin-1 reduces oxidative stress both smooth muscle cells. Pathological stimuli-induced cell proliferation, vascular remodeling, arterial stiffness can be ameliorated as well. In addition, also modulates immune function, inhibition infiltration into wall, improves function perivascular adipose tissue. All these mechanisms contribute to protective effects on blood pressure vivo. Sirtuin 1, AMP-activated protein kinase, estrogen receptors represent major molecules mediating resveratrol.

Language: Английский

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Resveratrol Inhibits HCoV-229E and SARS-CoV-2 Coronavirus Replication In Vitro

Viruses, Journal Year: 2021, Volume and Issue: 13(2), P. 354 - 354

Published: Feb. 23, 2021

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China at the end of 2019 causing a large global outbreak. As treatments are utmost importance, drug repurposing embodies rich and rapid discovery landscape, where candidate compounds could be identified optimized. To this end, we tested seven for their ability to reduce replication human (HCoV)-229E, another member family. Among these drugs tested, four them, namely rapamycin, disulfiram, loperamide valproic acid, were highly cytotoxic did not warrant further testing. In contrast, observed reduction viral titer by 80% with resveratrol (50% effective concentration (EC50) = 4.6 µM) lopinavir/ritonavir (EC50 8.8 60% chloroquine 5 very limited cytotoxicity. three drugs, was less (cytotoxic 50 (CC50) 210 than (CC50 102 67 µM). Thus, among against HCoV-229E, demonstrated optimal antiviral response low cytotoxicity selectivity index (SI) 45.65. Similarly, an anti-HCoV-229E activity, lopinavir/ritonavir, resveratrol, only latter showed on SARS-CoV-2 reduced This opens door evaluation fight Covid-19.

Language: Английский

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COVID‐19: immunopathology, pathophysiological mechanisms, and treatment options

The Journal of Pathology, Journal Year: 2021, Volume and Issue: 254(4), P. 307 - 331

Published: Feb. 17, 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures combat disease. Although most COVID-19 cases are characterised a mild, self-limiting course, considerable subset patients develop more condition, varying from pneumonia and distress (ARDS) multi-organ failure (MOF). Progression is thought occur as result complex interplay between multiple pathophysiological mechanisms, all which may orchestrate SARS-CoV-2 infection contribute organ-specific tissue damage. In this respect, dissecting currently available knowledge immunopathogenesis crucially important, not only improve our understanding its pathophysiology but also fuel rationale both novel repurposed treatment modalities. Various immune-mediated pathways during relevant in context, relate innate immunity, adaptive autoimmunity. Pathological findings specimens with provide valuable information regard well development evidence-based regimens. This review provides an updated overview main pathological changes observed within commonly affected organ systems, special emphasis on immunopathology. Current management strategies for include supportive care use or symptomatic drugs, such dexamethasone, remdesivir, anticoagulants. Ultimately, prevention key COVID-19, requires appropriate attenuate and, above all, effective vaccines. © 2021 The Authors. Journal Pathology published John Wiley & Sons, Ltd. behalf Society Great Britain Ireland.

Language: Английский

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The Effects of Resveratrol in the Treatment of Metabolic Syndrome

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(3), P. 535 - 535

Published: Jan. 28, 2019

Resveratrol, also known as 3,5,4′-trihydroxystilbene, is a natural polyphenol that occurs phytoalexin. It produced by plant sources such grapes, apples, blueberries, plums, peanuts, and other oilseeds. This compound has variety of effects on human health diseases. review summarizes the mounting evidence resveratrol helpful in treating metabolic syndrome related disorders. Resveratrol can be provided either early reprogramming agent or later part treatment. A few main mechanisms underlying beneficial are outlined. discusses potential derivatives complementary alternative medicine. In conclusion, could useful regimen for prevention treatment its conditions.

Language: Английский

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The Role of Sirtuin1 in Regulating Endothelial Function, Arterial Remodeling and Vascular Aging

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: Sept. 12, 2019

Sirtuin1 (SIRT1), which belongs to a highly conserved family of protein deacetylase, is one the best-studied sirtuins. SIRT1 involved in variety biological processes, including energy metabolism, cell proliferation and survival, chromatin dynamics, DNA repair. In vasculature, ubiquitously expressed endothelial cells, smooth muscle perivascular adipose tissues (PVAT). Endothelial plays unique role vasoprotection by regulating large proteins, nitric oxide synthase (eNOS). eNOS regulate each other synergistically through positive feedback mechanisms for maintenance function. Recent studies have shown that vital modulating PVAT function, arterial remodeling, vascular aging. present article, we summarize recent findings, review molecular potential as therapeutic target treatment diseases, discuss future research directions.

Language: Английский

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Accelerated Kidney Aging in Diabetes Mellitus

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 24

Published: July 28, 2020

With aging, the kidney undergoes inexorable and progressive changes in structural functional performance. These aging-related alterations are more obvious serious diabetes mellitus (DM). Renal accelerated aging under DM conditions is associated with multiple stresses such as accumulation of advanced glycation end products (AGEs), hypertension, oxidative stress, inflammation. The main hallmarks cellular senescence diabetic kidneys include cyclin-dependent kinase inhibitors, telomere shortening, nephropathy-associated secretory phenotype. Lysosome-dependent autophagy antiaging proteins Klotho Sirt1 play a fundamental role DM, among which autophagy-lysosome system convergent mechanism pathways involved renal conditions. Metformin inhibitor sodium-glucose cotransporter 2 recommended due to their effects independent antihyperglycemia, besides angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Additionally, diet intervention including low protein AGEs antioxidants suggested for patients nephropathy (DN). However, long-term benefits still need further study. Exploring interactive relationships Klotho, Sirt1, may provide insight into better satisfying urgent medical needs elderly DN.

Language: Английский

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Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 11, 2020

Age-related disorders such as chronic kidney disease (CKD) are increasingly prevalent globally and pose unprecedented challenges. In many aspects, CKD can be viewed a state of accelerated premature aging. Aging share common characteristic features with increased cellular senescence, conserved program characterized by an irreversible cell cycle arrest altered transcriptome secretome. While developmental senescence acute may positively contribute to the fine-tuning embryogenesis injury repair, when unresolved promptly, plays crucial role in fibrogenesis progression. Senescent cells elicit their fibrogenic actions primarily secreting assortment inflammatory profibrotic factors known senescence-associated secretory phenotype (SASP). Increasing evidence indicates that senescent could promising new target for therapeutic intervention senotherapy, which includes depleting cells, modulating SASP restoration inhibitors. this review, we discuss current understanding mechanism fibrosis. We also highlight potential options targeting treatment CKD.

Language: Английский

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The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(18), P. 10152 - 10152

Published: Sept. 21, 2021

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies RES focused on its favorable pathological conditions related to cardiovascular and their risk factors. aim this review was summarize wide beneficial system, including signal transduction pathways cell longevity, energy metabolism cardiomyocytes or cardiac remodeling, anti-inflammatory antioxidant properties. In addition, paper discusses significant preclinical human clinical trials years with system. Finally, we present a short overview antiviral properties possible future perspectives against COVID-19 in diseases.

Language: Английский

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