How COVID-19 shaped mental health: from infection to pandemic effects

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(10), P. 2027 - 2037

Published: Oct. 1, 2022

Language: Английский

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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 7, 2022

Abstract Molecular oxygen (O 2 ) is essential for most biological reactions in mammalian cells. When the intracellular content decreases, it called hypoxia. The process of hypoxia linked to several processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, other stress responses. mechanism underlying cells respond changes mediate subsequent signal response central question during Hypoxia-inducible factors (HIFs) sense regulate expressions a series downstream genes expression, which participate multiple processes cell metabolism, growth/death, proliferation, glycolysis, immune response, tumorigenesis, metastasis. Importantly, signaling also interacts with cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) endoplasmic reticulum (ER) stress. This paper systematically reviews mechanisms activation, control HIF function human health diseases. In addition, therapeutic targets involved balance diseases are summarized highlighted, would provide novel strategies design development drugs.

Language: Английский

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Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(3), P. 1850 - 1861

Published: Jan. 13, 2022

Language: Английский

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Neuroinflammation and COVID-19

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 76, P. 102608 - 102608

Published: June 29, 2022

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection the central nervous system (CNS) by SARS-CoV-2, thus what causing disease? Here, we review potential immunological mechanisms driving in patients. We begin discussing implications imbalanced peripheral immunity on CNS function. Next, examine for dysregulation blood-brain barrier during SARS-CoV-2 infection. Last, discuss role myeloid cells may play promoting Combined, highlight innate neuroinflammation suggest areas future research.

Language: Английский

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‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA

Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2287 - 2287

Published: Aug. 17, 2023

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. production of ‘safe effective’ vaccines was a key public health target. Sadly, unprecedented high rates adverse events have overshadowed the benefits. This two-part narrative review presents evidence for widespread harms novel product mRNA adenovectorDNA is in attempting provide thorough overview arising from new technology that relied on human cells producing foreign antigen has pathogenicity. first paper explores peer-reviewed data counter attached these technologies. Spike protein pathogenicity, termed ‘spikeopathy’, whether SARS-CoV-2 virus or produced by vaccine gene codes, akin ‘synthetic virus’, increasingly understood terms molecular biology pathophysiology. Pharmacokinetic transfection through body tissues distant injection site lipid-nanoparticles viral-vector carriers means ‘spikeopathy’ can affect organs. inflammatory properties nanoparticles used ferry mRNA; N1-methylpseudouridine employed prolong synthetic function; biodistribution DNA codes translated spike proteins, autoimmunity via contribute harmful effects. reviews autoimmune, cardiovascular, neurological, potential oncological effects, autopsy spikeopathy. With gene-based therapeutic technologies planned, re-evaluation necessary timely.

Language: Английский

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The Role of Nuclear Factor Kappa B (NF-κB) in Development and Treatment of COVID-19: Review

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 5283 - 5283

Published: May 9, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 19 (COVID-19), a disease that has affected more than 500 million people worldwide since the end of 2019. Due to its high complications and death rates, there is still need find best therapy for SARS-CoV-2 infection. The dysregulation inflammatory response in COVID-19 plays very important role progression. It been observed abnormal activity Nuclear Factor kappa B (NF-κB) directly associated with, inter alia, increased synthesis proinflammatory factors. Therefore, this review paper focuses on functions NF-κB development infection potential application inhibitors immunotherapy. A comprehensive literature search was performed using MEDLINE/PubMed database. In current review, it highlighted modulation an adaptive response, including inducing expression genes. Increased activation observed. association between structural non-structural proteins were also reported. using, e.g., traditional Chinese medicine or glucocorticosteroids resulted decreased factors caused by This summarizes describes immunotherapeutic target treatment However, indisputably studies involving patients with severe course are sorely needed.

Language: Английский

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Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 451 - 451

Published: Feb. 3, 2023

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses Spike proteins of its envelope infecting target cells expressing on membrane angiotensin converting enzyme 2 (ACE2) that acts as a receptor. To control pandemic, genetically engineered vaccines have been designed inducing neutralizing antibodies against proteins. These do not act like traditional protein-based vaccines, they deliver message in form mRNA or DNA to host then produce and expose protein (from which it can be shed soluble form) alert immune system. Mass vaccination has brought light various adverse effects associated with these based mainly affecting circulatory cardiovascular ACE2 is present membrane-bound several cell types, including mucosa upper gastrointestinal tracts, endothelium, platelets, plasma. converts vasoconstrictor II into peptides vasodilator properties. Here we review pathways immunization molecular mechanisms through protein, either from encoded by mRNA-based interferes Renin-Angiotensin-System governed ACE2, thus altering homeostasis circulation Understanding interactions consequent impact system will direct diagnosis therapy vaccine-related provide information development personalized considers pathophysiological conditions predisposing such events.

Language: Английский

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Pericyte Loss in Diseases

Cells, Journal Year: 2023, Volume and Issue: 12(15), P. 1931 - 1931

Published: July 26, 2023

Pericytes are specialized cells located in close proximity to endothelial within the microvasculature. They play a crucial role regulating blood flow, stabilizing vessel walls, and maintaining integrity of blood–brain barrier. The loss pericytes has been associated with development progression various diseases, such as diabetes, Alzheimer’s disease, sepsis, stroke, traumatic brain injury. This review examines detection pericyte different explores methods employed assess coverage, elucidates potential mechanisms contributing these pathological conditions. Additionally, current therapeutic strategies targeting discussed, along future interventions aimed at preserving function promoting disease mitigation.

Language: Английский

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Mechanisms of coronavirus infectious disease 2019-related neurologic diseases

Current Opinion in Neurology, Journal Year: 2022, Volume and Issue: 35(3), P. 392 - 398

Published: March 11, 2022

Purpose of review As January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, new RNA virus, has resulted in 304,896,785 cases over 222 countries and regions, 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports neurological psychiatric symptoms the context infectious disease 2019 (COVID-19) range from headache, anosmia, dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, hemorrhagic necrotizing encephalopathy. Moreover, 30–50% COVID-19 survivors develop long-lasting neurologic symptoms, including dysexecutive syndrome, inattention disorientation, and/or poor movement coordination. Detection SARS-CoV-2 within central nervous system (CNS) patients is rare, mechanisms damage ongoing diseases are unknown. However, studies demonstrating viral glycoprotein effects on coagulation cerebral vasculature, hypoxia- cytokine-mediated coagulopathy CNS immunopathology suggest both virus-specific neuroimmune responses may be involved. This explores potential mechanistic insights that could contribute COVID-19-related disease. Recent findings While development during rarely associated evidence neuroinvasion, suggests Spike (S) protein exhibits direct pro-coagulation effects. This, conjunction immune dysregulation resulting cytokine release (CRS) result cerebrovascular or neuroinflammatory diseases. Additionally, CRS-mediated loss blood-brain barrier integrity specific brain regions expression proinflammatory mediators neural cells impact function long after resolution infection. Importantly, host co-morbid affect vascular, pulmonary, type triggered SARS-COV-2 Summary Distinct S compartment- region-specific CRS underlie chronic COVID-19.

Language: Английский

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Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

JCI Insight, Journal Year: 2022, Volume and Issue: 7(16)

Published: July 19, 2022

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role the pathogenesis severity of COVID-19; however, its pediatric manifestations this disease, including multisystem inflammatory syndrome children (MIS-C) chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, CLLs, NETs were significantly increased serum skin. There was geographic variability prevalence MIS-C, association with disease severity. MIS-C CLL samples displayed decreased NET ability, C1q G-actin or anti-NET antibodies, respectively, but not genetic variants DNases. In adult COVID-19, persistent elevations after diagnosis detected did occur asymptomatic infection. COVID-19–affected adults significant impaired degradation, anti-DNase1L3, G-actin, specific manifestations, many organs patients who died from COVID-19 complications. Infection Omicron variant associated levels when compared other SARS-CoV-2 strains. These data support for patients.

Language: Английский

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