ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19 DOI Creative Commons
Marie Lykke Bach,

Sara Laftih,

Jesper Kingo Andresen

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 9, 2024

Abstract SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that TMPRSS2 proteins more abundant (1) males increasing kidney (2) urine extracellular vesicles (EVs) from patients COVID-19 (3) present EVs during infection. Kidney cortex samples subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 15) were analyzed protein levels. Urine hospitalized infection was uEVs used immunoblotting mRNA antigen detection. Tissue levels did not change age. kidneys any group. associated proximal tubule apical membranes cortex. observed predominantly the medulla. elevated significantly no sex difference compared controls w/wo albuminuria. female. co-localize uEVs/apical membranes. nucleoprotein detected urine. Higher abundance unlikely explain higher susceptibility males. tubular appear susceptible Loss of into COVID could impact angiotensin metabolism.

Язык: Английский

Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective DOI Creative Commons
Stefano Sanduzzi Zamparelli, Alessandro Sanduzzi, Marialuisa Bocchino

и другие.

Life, Год журнала: 2025, Номер 15(1), С. 113 - 113

Опубликована: Янв. 16, 2025

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly impacted global health, with pneumonia emerging as a major complication in severe cases. pathogenesis of is marked the overproduction reactive oxygen species (ROS) and an excessive inflammatory response, resulting oxidative stress significant tissue damage, particularly respiratory system. Antioxidants have garnered considerable attention for their potential role managing mitigating modulating immune responses. This review provides comprehensive overview literature on use antioxidants hospitalized patients mild-to-moderate COVID-19. Studies exploring antioxidants, including vitamins, trace elements, nitric oxide (NO), ozone (O3), glutathione (GSH), L-carnitine, melatonin, bromelain, N-acetylcysteine (NAC), numerous polyphenols, yielded promising outcomes. Through ROS-scavenging properties, these molecules support endothelial function, reduce thrombosis risk, may help mitigate effects cytokine storm, key contributor to morbidity mortality. Clinical evidence suggests that antioxidant supplementation improve patient outcomes decreasing inflammation, supporting cell potentially shortening recovery times. Furthermore, symptoms exerting direct antiviral inhibit infection process genomic replication SARS-CoV-2 host cells. Moreover, work synergistically standard treatments viral-induced damage. By integrating findings from real-world data our clinical experience, we gain more profound understanding pneumonia. Further research combining reviews analysis crucial validate efficacy establish evidence-based guidelines practice.

Язык: Английский

Процитировано

1

Morphopathology of the lesions induced by SARS-CoV-2 infection in the lungs DOI Open Access

Florin Ionuţ Buibaş,

Roberta Andreea Cercel,

Mircea-Sebastian Șerbănescu

и другие.

Romanian Journal of Morphology and Embryology, Год журнала: 2025, Номер 65(4), С. 637 - 645

Опубликована: Фев. 13, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spread rapidly from China around the world, causing worst pandemic since beginning of 21st century. Although disease named 2019 (COVID-19) has multiple organ symptoms, main pathological lesions occur in lung, failure, pulmonary embolism, secondary bacterial pneumonia and fibrosis. Despite best efforts researchers, pathogenesis SARS-CoV-2-induced cellular tissue damage organs systems is poorly understood. Therefore, our study, we aimed to highlight their extent, which could explain complex symptomatology presented by patients who died with distress (ARDS). The study was performed on a number 36 diagnosed COVID-19 under legally suspicious conditions, requiring autopsy within Romanian Forensic Medicine Institutes. All local inflammatory reaction pneumonic type, exudative proliferative phenomena, intra-alveolar interstitial infiltrates formed lymphocytes, macrophages neutrophilic granulocytes, congested or ruptured blood vessels hemorrhages, thrombosis, proliferation fibroblasts transformed into myofibroblasts presence granulation that remodeled entire lung parenchyma.

Язык: Английский

Процитировано

0

Unlocking the potential of the ACE2/Ang‐(1–7)/Mas Axis in liver diseases: From molecular mechanisms to translational applications DOI

Jun Yang,

Yuan Yang,

Xiangyun Tan

и другие.

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Май 9, 2025

Abstract Over the past two decades, identification of new functions within renin–angiotensin system (RAS) has extended beyond its traditional roles, with emergence angiotensin‐converting enzyme 2 (ACE2)/Ang‐(1–7)/Mas axis being particularly significant. This is hypothesized to balance or modulate effects ACE/Ang II/AT1 in various physiological and pathological contexts. ACE2, a membrane‐bound carboxypeptidase an ancient homologue ACE converts Angiotensin II (Ang II) into 1–7 (Ang‐(1–7)). The Mas receptor G‐protein‐coupled that specifically binds Ang‐(1–7). Recent research increasingly focused on local expression RAS different tissues. Ang‐(1–7) produces variety biological by binding receptor, including anti‐inflammatory, antioxidant, anti‐apoptotic anti‐fibrotic actions, thereby influencing range mechanisms heart, kidneys, brain other Preclinical animal model studies indicate manipulating protective can significantly alter progression multiple liver diseases. Hepatic overexpression ACE2 administration analogues been shown be therapeutically effective against drug‐induced injury, metabolic‐associated fatty disease, fibrosis hepatocellular carcinoma progression. These are achieved through pathways, regulation lipid metabolism, inhibition epithelial–mesenchymal transition (EMT) extracellular matrix (ECM) production, as well suppression aerobic glycolysis. In current clinical trials, while recombinant human (Rh‐ACE2) demonstrated safety good tolerance most studies, relevance activating ACE2/Ang‐(1–7) evolution diseases remains early stages. Therefore, further elucidation complex interactions between classical counter‐regulatory axes settings crucial. review will summarize roles selective activation ACE2/Ang‐(1–7)/Mas axis, focus treatment Additionally, we discuss concerns regarding applications challenges tissue‐specific this providing therapeutic strategies for targeted hepatic practice.

Язык: Английский

Процитировано

0

COVID-19 – multisystem disease DOI Open Access

Roberta Andreea Cercel,

Florin Ionuţ Buibaş,

Mircea-Sebastian Șerbănescu

и другие.

Romanian Journal of Morphology and Embryology, Год журнала: 2025, Номер 66(1), С. 61 - 67

Опубликована: Май 15, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for disease 2019 (COVID-19), caused a global public health crisis, with significant impact on multiple body systems. This virus, member of Coronaviridae family, shows ~80% genomic similarity to SARS-CoV and ~50% Middle East (MERS-CoV). The spike (S) protein plays an essential role in pathogenesis as it facilitates its entry into host cells by binding angiotensin-converting enzyme (ACE2) receptor. In addition system damage, SARS-CoV-2 infection causes variety gastrointestinal (GI), neurological, cardiovascular (CV), ocular, renal, etc. clinical manifestations. Neurological complications, such anosmia, ague, headache, encephalitis cerebrovascular events, were frequently observed, being attributed both direct viral invasion very strong systemic inflammatory response. GI symptoms diarrhea, nausea vomiting are common may occur independently symptoms, presence ribonucleic acid (RNA) detected fecal samples suggests possible fecal-oral transmission. CV is affected myocardial inflammation coagulation disorders, increased risk thromboembolic events. At ocular level, was identified secretions, conjunctivitis, uveitis episcleritis observed about 11% patients. Renal involvement, manifested kidney injury, 0.5-7% cases. conclusion, not limited tract involvement but also has implications.

Язык: Английский

Процитировано

0

SARS-CoV-2 point mutations are over-represented in terminal loops of RNA stem-loop structures that can be resolved by Nsp13 helicase in a unique manner with respect to nucleotide dependence DOI Creative Commons
Adaira J. Dumm, Allen Zheng, Thomas Bütler

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(10)

Опубликована: Май 22, 2025

Abstract To improve health outcomes for COVID-19 (coronavirus disease 2019) patients, the factors that influence coronavirus genome variation need to be ascertained. The SARS-CoV-2 (severe acute respiratory syndrome 2) is rich in predicted RNA secondary structures, particularly stem-loops (SLs) formed by intramolecular base pairing within palindromic sequences. We analyzed NCBI Virus collection of sequences from individuals map variants relative SL structural elements. Point mutations genome, with a C-to-U transition bias, were over-represented unpaired nucleotides and, more specifically, terminal loops structures. As sole helicase encoded SARS-CoV-2, Nsp13 may operate timely resolution structures facilitate copying or processing. characterized resolve sequence-derived unimolecular substrates and determined it does so functionally cooperative manner. In addition ATP, resolves structure absence nucleotide, contrast strict ATP requirement bimolecular forked duplex. suggest model which series binary ternary complex interactions nucleotide and/or pose mechanistic implications resolution.

Язык: Английский

Процитировано

0

The Role of Long-Range Non-Specific Electrostatic Interactions in Inhibiting the Pre-Fusion Proteolytic Processing of the SARS-CoV-2 S Glycoprotein by Heparin DOI Creative Commons
Yi Du, Yang Yang, Son Nguyen

и другие.

Biomolecules, Год журнала: 2025, Номер 15(6), С. 778 - 778

Опубликована: Май 28, 2025

The proteolytic processing of the SARS-CoV-2 spike glycoprotein by host cell membrane-associated proteases is a key step in both entry invading virus into and release newly generated viral particles from infected cell. Because critical importance this for infectivity cycle, it has been target extensive efforts aimed at identifying highly specific protease inhibitors as potential antiviral agents. An alternative strategy to disrupt pre-fusioviden S aims protect substrate rather than directly inhibit proteases. In work, we focused on furin, serine located primarily Golgi apparatus, but also present membrane. Its cleavage site within stalk region latter comprises an arginine-rich segment (SPRRARS), which fits definition Cardin–Weintraub glycosaminoglycan recognition motif. Native mass spectrometry (MS) measurements confirmed binding hexadecameric peptide representing loop S1/S2 interface incorporating furin (FCS) heparin fragments various lengths, well unfractionated (UFH), although physiological ionic strength, only UFH remains tightly bound FCS. direct LC/MS monitoring FCS digestion with revealed significant impact proteolysis kinetics, had IC50 values that could be considered physiologically relevant (0.6 ± 0.1 mg/mL). results work highlight long-range relatively non-specific electrostatic interactions modulating pathological processes emphasize multi-faceted role played managing coronavirus infections.

Язык: Английский

Процитировано

0

ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19 DOI Creative Commons
Marie Lykke Bach,

Sara Laftih,

Jesper Kingo Andresen

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 9, 2024

Abstract SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that TMPRSS2 proteins more abundant (1) males increasing kidney (2) urine extracellular vesicles (EVs) from patients COVID-19 (3) present EVs during infection. Kidney cortex samples subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 15) were analyzed protein levels. Urine hospitalized infection was uEVs used immunoblotting mRNA antigen detection. Tissue levels did not change age. kidneys any group. associated proximal tubule apical membranes cortex. observed predominantly the medulla. elevated significantly no sex difference compared controls w/wo albuminuria. female. co-localize uEVs/apical membranes. nucleoprotein detected urine. Higher abundance unlikely explain higher susceptibility males. tubular appear susceptible Loss of into COVID could impact angiotensin metabolism.

Язык: Английский

Процитировано

1