Damage to endothelial barriers and its contribution to long COVID

Angiogenesis, Journal Year: 2023, Volume and Issue: 27(1), P. 5 - 22

Published: April 27, 2023

Language: Английский

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Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 4968 - 4976

Published: July 4, 2023

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience number of persistent neurological psychiatric known as long COVID or "brain fog". Studies autopsy samples from who died COVID-19 detected the brain. Furthermore, increasing evidence shows that Epstein-Barr virus (EBV) reactivation after might play role symptoms. Moreover, alterations microbiome contribute this article, author reviews detrimental effects on brain, biological mechanisms (e.g., EBV reactivation, changes gut, nasal, oral, lung microbiomes) underlying COVID. addition, discusses potential therapeutic approaches based gut-brain axis, including plant-based diet, probiotics prebiotics, fecal microbiota transplantation, vagus nerve stimulation, sigma-1 receptor agonist fluvoxamine.

Language: Английский

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Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 262 - 262

Published: Jan. 9, 2023

The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is most common site of infection, a significant number reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although mechanisms pathogenesis are still being examined, viral components isolated from stool samples infected patients suggest potential fecal–oral transmission route. In addition, RNA has been detected in blood patients, making hematologic dissemination virus proposed route for Angiotensin-converting enzyme 2 (ACE2) receptors serve as cellular entry mechanism virus, these particularly abundant throughout tract, intestine, liver, pancreas extrapulmonary sites infection reservoirs developing mutations new variants that contribute to uncontrolled disease resistance treatments. This dysregulation immune play role profound inflammatory coagulative cascades increased severity risk death several COVID-19 patients. article reviews various gastrointestinal, pancreatic injury.

Language: Английский

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Intestinal barrier dysfunction as a key driver of severe COVID-19

World Journal of Virology, Journal Year: 2023, Volume and Issue: 12(2), P. 68 - 90

Published: March 21, 2023

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with immune cells and epithelial endothelial cells, forming multi-layered barrier enables the efficient absorption nutrients without an excessive influx pathogens. Despite being lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including gastrointestinal tract pertinent gut function. Severe acute respiratory syndrome 2 (SARS-CoV-2) can inflict either direct cytopathic injury to or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines structural integrity by modifying expression tight junction proteins. In addition, induces profound alterations microflora at phylogenetic metabolomic levels (dysbiosis) are accompanied disruption local responses. ensuing dysregulation gut-lung axis impairs ability system elicit robust timely responses restrict viral infection. vasculature is vulnerable SARS-CoV-2-induced injury, which simultaneously triggers activation innate coagulation condition referred as "immunothrombosis" drives thrombotic complications. Finally, increased permeability allows aberrant dissemination bacteria, fungi, endotoxin into systemic circulation contributes, certain degree, over-exuberant hyper-inflammation dictate form COVID-19. this review, we aim elucidate SARS-CoV-2-mediated effects on homeostasis their implications progression disease.

Language: Английский

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cGAS-STING signaling pathway in intestinal homeostasis and diseases

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

Published: Sept. 14, 2023

The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. consists of multiple differentiated cellular extracellular that form a critical barrier, but also equipped for efficient absorption nutrients. Combination genetic susceptibility factors are known as involved in the pathogenesis diseases. innate immune system plays role recognition elimination potential threats by detecting pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs). This host defense facilitated pattern receptors (PRRs), which cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has gained attention due its sensing foreign double-stranded DNA (dsDNA) well dinucleotides (CDNs) produced bacteria. Upon binding with dsDNA, cGAS converts ATP GTP (cGAMP), binds STING activates TANK kinase 1 (TBK1) regulatory factor 3 (IRF3), inducing type I (IFN) nuclear kappa B (NF-κB)-mediated pro-inflammatory cytokines, have diverse effects on adaptive cells epithelial (IECs). However, opposite perspectives exist regarding cGAS-STING different Activation signaling associated worse clinical outcomes inflammation-associated diseases, while it protection against tumorigenesis certain infections. Therefore, understanding context-dependent mechanisms physiopathology crucial developing therapeutic strategies targeting pathway. review aims provide insight into recent findings protective detrimental roles

Language: Английский

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Oligosaccharides as Potential Regulators of Gut Microbiota and Intestinal Health in Post-COVID-19 Management

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(6), P. 860 - 860

Published: June 9, 2023

The COVID-19 pandemic has had a profound impact worldwide, resulting in long-term health effects for many individuals. Recently, as more and people recover from COVID-19, there is an increasing need to identify effective management strategies post-COVID-19 syndrome, which may include diarrhea, fatigue, chronic inflammation. Oligosaccharides derived natural resources have been shown prebiotic effects, emerging evidence suggests that they also immunomodulatory anti-inflammatory could be particularly relevant mitigating the of COVID-19. In this review, we explore potential oligosaccharides regulators gut microbiota intestinal management. We discuss complex interactions between microbiota, their functional metabolites, such short-chain fatty acids, immune system, highlighting improve manage syndrome. Furthermore, review with angiotensin-converting enzyme 2 expression alleviating Therefore, offer safe, natural, approach potentially improving health, overall outcomes

Language: Английский

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3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10071 - 10071

Published: Sept. 3, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat global health. Enormous efforts have been made by researchers around world elucidate COVID-19 pathophysiology, design efficacious therapy develop new vaccines control pandemic. To this end, experimental models are essential. While animal conventional cell cultures widely utilized during these research endeavors, they often do not adequately reflect human responses SARS-CoV-2 infection. Therefore, that emulate with high fidelity infection in organs needed for discovering antiviral drugs against COVID-19. Three-dimensional (3D) cultures, such as lung organoids bioengineered organs-on-chips, emerging crucial tools on diseases. The airway, small airway alveolus organ chips successfully used studies response various pathogens, including corona influenza A viruses. In review, we provide an overview of their use pathogenesis drug testing. We also discuss limitations existing indicate some improvements well future epidemics.

Language: Английский

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Lipid rafts disruption by statins negatively impacts the interaction between SARS-CoV-2 S1 subunit and ACE2 in intestinal epithelial cells

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The causative agent of the COVID-19 pandemic, SARS-CoV-2, is a virus that targets mainly upper respiratory tract. However, it can affect other systems such as gastrointestinal (GI) Therapeutic strategies for this are still inconclusive and understanding its entry mechanism important finding effective treatments. Cholesterol an constituent in structure cellular membranes plays crucial role variety events. In addition, infectivity pathogenicity several viruses. ACE2, main receptor associated with lipid rafts which microdomains composed cholesterol sphingolipids. study, we investigate statins, lipid-lowering drugs, on trafficking ACE2 impact modulation interaction S1 Caco-2 cells. data show fluvastatin simvastatin reduce expression to variable extents, impair association sorting brush border membrane resulting substantial reduction subunit spike protein. By virtue effects statins demonstrated our these molecules, particularly fluvastatin, represent promising therapeutic intervention be used off-label treat SARS-CoV-2.

Language: Английский

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Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)

Published: March 23, 2023

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after clearance. Despite vaccination and existing antiviral treatments, variants concern are still emerging circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies demonstrate an increased preference for entry via endocytic route. Alternative direct-acting antivirals, host-directed therapies interfere host mechanisms hijacked by viruses, enhance cell-mediated resistance reduced likelihood drug development. Here, we that autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents acquisition human intestinal epithelial cells autophagy-mediated BNIP3 mechanism. Strikingly, exhibited pan-antiviral activity against subvariants BA.2 at nanomolar potency, providing proof concept potential targeting autophagy machinery thwart infection current circulating subvariants. Furthermore, show limited virus-induced damage barrier function, affirming relevance manipulation avert permeability associated acute post-COVID-19 syndrome. Our findings underscore exploits dissemination indicate repurposed autophagy-based antivirals represent pertinent option boost protection ameliorate disease pathogenesis future concern.

Language: Английский

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Preferential apical infection of Caco-2 intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the pathophysiology of COVID-19

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0313068 - e0313068

Published: Feb. 10, 2025

SARS-CoV-2 can infect different organs, including the intestine. In an in vitro model of Caco-2 intestinal cell line, we previously found that modulates ACE2 receptor expression and affects molecules involved intercellular junctions. To further explore possibility epithelium serve as alternative infection route for SARS-CoV-2, used a polarized monolayers cells (or co-cultures two lines: HT29) grown on polycarbonate membrane Transwell inserts, inoculated with virus either upper or lower chamber culture to determine tropism apical basolateral pole these cells. both co-culture Caco-2/HT29 monolayer, inoculation was be much more effective establishing than inoculation. addition, triggers monolayer degeneration, shown by histological examination, measurement trans-epithelial electrical resistance, adhesion molecule expression. During infection, infectious viruses reach chamber, suggesting transcytosis mechanism from side cells, paracellular trafficking after damage junctions epithelial barrier, both. Taken together, data indicate preferential human tract suggest via lumen leads systemic infection.

Language: Английский

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