The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders

Life, Год журнала: 2024, Номер 14(2), С. 279 - 279

Опубликована: Фев. 19, 2024

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this may long-term adverse neurological consequences. COVID-19 occurs from infection by positive-sense single-stranded RNA virus called severe acute respiratory syndrome 2 (SARS-CoV-2). The membrane fusion protein SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme (ACE2), initiate between and cell. SARS-CoV-2 contains furin protease recognition site cleavage enhances infectivity virus. binding ACE2 receptor has shown downregulate ACE2, thereby increasing levels pathogenic angiotensin II (Ang II). cleaves S1 subunit with domain toward S2 transmembrane anchors viral membrane, activity releases into blood circulation. released also downregulates turn level Ang II. Considering particle many molecules, furin-dependent would release free each which can while only affects one molecule. Therefore, dramatically amplify ability produce We hypothesize amplification mechanism possesses, but not per se, is major driving force behind COVID-19-associated disorders.

Язык: Английский

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Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Апрель 4, 2024

SARS-CoV-2-induced excessive inflammation in brain leads to damage of blood-brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production inflammatory cytokines by microvascular endothelial cells microglia is reported be critically associated with the pathology COVID-19 patients. However, cellular mechanisms for SARS-CoV-2-inducing activation subsequent neuroinflammation remain fully delineated. Our research, along others', has recently demonstrated that accumulation mast (MCs) mouse lung could further induce consequent damages. Intracerebral MCs their cross talk other play important roles neurodegenerative diseases including virus-induced neuro-pathophysiology. In this study, we investigated role MC neuroinflammation. We found (1) SARS-CoV-2 infection triggered cerebrovascular region mice; (2) spike/RBD (receptor-binding domain) protein-triggered induced factors human microglia; (3) degranulation destroyed tight junction proteins proliferation microglia. These findings reveal a mechanism

Язык: Английский

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Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Июль 15, 2024

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is known to infect people all ages and both sexes. Senior populations have greatest risk severe sexual dimorphism in clinical outcomes has been reported. Neurological symptoms are widely observed COVID-19 patients, with many survivors exhibiting persistent neurological cognitive impairment. The present study aims investigate impact age sex on neuroinflammatory response SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6J mice were intranasally inoculated lineage B.1.351, variant mice. Older male exhibited significantly greater weight loss higher viral loads lung at 3 days post infection. Notably, no RNA was detected brains infected Nevertheless, expression IL-6, TNF-α, CCL-2 brain increased RNA-seq transcriptomic analysis showed that caused significant changes gene profiles, implicating innate immunity, defense virus, cerebrovascular neuronal functions. These findings demonstrate triggers response, despite lack detectable virus brain. Aberrant activation immune disruption blood-brain barrier endothelial cell integrity, suppression activity axonogenesis underlie Understanding role these affected pathways pathogenesis helps identify appropriate points therapeutic interventions alleviate dysfunction during COVID-19.

Язык: Английский

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Antiviral Effect and Mechanism of Ma-Xing-Shi-Gan-San Against Porcine Reproductive and Respiratory Syndrome Virus Via Network Pharmacology and Molecular Docking

Опубликована: Янв. 1, 2025

Язык: Английский

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On the post-COVID syndrome pathogenesis

Cytokines and inflammation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

In 2023, the pandemic of new coronavirus infection caused by SARS-CoV-2 was declared over WHO. Apparently, has become a seasonal respiratory viral infection. Among problems remaining after end pandemic, one leading places is occupied post-Covid syndrome - condition associated with persistence symptoms COVID-19 or reappearance 3 months illness. Most common features are: immune dysregulation, persistence, continued systemic inflammation, autoimmune dysorders, tromboses and endothelial damage, myocarditis, ischemic cardial disease, lung fibrosis. These different organ dysfunctions are accompanied neurological complications. Precise pathophysiological mechanisms to be discovered. The review addresses issues pathogenesis syndrome.

Язык: Английский

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Spike protein-related proteinopathies: a focus on the neurological side of spikeopathies

Annals of Anatomy - Anatomischer Anzeiger, Год журнала: 2025, Номер unknown, С. 152662 - 152662

Опубликована: Апрель 1, 2025

Язык: Английский

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Antiviral effects and mechanism of Ma-Xing-Shi-Gan-San on porcine reproductive and respiratory syndrome virus

Frontiers in Microbiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 29, 2025

Background Currently, vaccination has consistently posed challenges in preventing the Porcine reproductive and respiratory syndrome virus (PRRSV), so there is an urgent need for effective controlling strategies. Ma-Xing-Shi-Gan-San (MXSGS), a traditional Chinese medicine (TCM) formula used pulmonary diseases disorders, proven treating H1N1 COVID-19. Herein, we evaluated whether MXSGS exhibits potent antiviral activity against PRRSV. Methods First, PRRSV-infected Marc-145 cell model was established. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tissue culture infective dose (TCID₅₀) assay were performed to assess inhibitory effects of on PRRSV during different administration stages. Network pharmacology then employed identify key active ingredients core potential targets In addition, gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses conducted elucidate signaling pathways modulated by MXSGS. Lastly, candidate validated molecular docking analysis. Results significantly inhibited through prophylactic therapeutic suppressed multiple phases viral life cycle, including attachment, internalization, replication, release. network results, 82 118 related identified. Among them, Calycosin, Odoratin, Glyzaglabrin, 7,2′,4′-trihydroxy-5-methoxy-3-arylcoumarin, Eriodictyol selected as ingredients. ALB, PPARG, CASP3, STAT3, TGFB1, JAK2, TLR4, PRKACA, PRKACB screened targets. Furthermore, pathway functional enrichment analysis revealed that impact mainly involved Toll-like receptor pathway, typical NF-κB signaling, positive regulation interleukin-6 production, Th17 differentiation, inflammatory response, defense response. indicated excellent binding affinity between ingredients, with all energies < −6.0 kcal/mol. Conclusion vitro experiments exhibited considerable anti-PRRSV activity. Using approaches, five six identified, underscoring promising pharmaceutical agent

Язык: Английский

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Luteolin Is More Potent than Cromolyn in Their Ability to Inhibit Mediator Release from Cultured Human Mast Cells

International Archives of Allergy and Immunology, Год журнала: 2024, Номер 185(8), С. 803 - 809

Опубликована: Янв. 1, 2024

<b><i>Introduction:</i></b> Mast cells are known for their involvement in allergic reactions but also inflammatory via secretion of numerous pro-inflammatory chemokines, cytokines, and enzymes. Drug development has focused on antiproliferative therapy systemic mastocytosis not inhibitors mast cell activation. The only drug available as a “mast blocker” is disodium cromoglycate (cromolyn), it poorly absorbed after oral administration, weak inhibitor histamine release from human cells, develops rapid anaphylaxis. Instead, certain natural flavonoids, especially luteolin, can inhibit <b><i>Methods:</i></b> Here, we compared pretreatment (0–120 min) with equimolar concentration (effective dose 50% inhibition = 100 m<sc>m</sc> by cromolyn) cromolyn luteolin mediators the cultured LADR line stimulated either immunoglobulin E (IgE) anti-IgE or IL-33. <b><i>Results:</i></b> We show that significantly more potent than inhibiting histamine, tryptase, metalloproteinase-9, vascular endothelial growth factor. Moreover, while inhibited IL-1β, IL-6, IL-8 (CXCL8) TNF, had no effect. <b><i>Conclusion:</i></b> These findings support use liposomal form to increase absorption, may be useful alternative cromolyn.

Язык: Английский

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Mast Cells: The Unregulated Master Immune Response Conductor

Allergy medicine., Год журнала: 2024, Номер 1, С. 100003 - 100003

Опубликована: Сен. 1, 2024

Mast cells (MC) are found perivascularly in all tissues and may function as the sentinel immune sensing danger then acting master conductor to orchestrate responses aimed at restoring homeostasis. Yet, MC best known for their critical role allergic, but also inflammatory other neuroimmune conditions. stimulated by allergens, many environmental, neuroimmune, pathogenic stress triggers. Stimulation of is called "activation" associated with release numerous neurohormonal, proinflammatory, tissue remodeling vasoactive mediators via different secretory mechanisms, some which do not involve histamine tryptase. However, mast cell activation subsequent become excessive either because persistent stimulation or dysregulation. Clinical experimental evidence indicates that be regulated innate molecules, derived from MC, themselves. discovery such innate, natural, inhibitors has been a priority even though they would substantially change treatment disorders (MCADs) since drugs available under development focus on inducing apoptosis. Development effective require access healthy MCAD subjects, preferably identical twins, allow differential investigation respective transcriptome.

Язык: Английский

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The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage

Stem Cell Reviews and Reports, Год журнала: 2024, Номер 20(8), С. 2062 - 2103

Опубликована: Авг. 16, 2024

Язык: Английский

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