Published: Jan. 1, 2024
Language: Английский
Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 519 - 519
Published: July 12, 2024
Glycolipid metabolic disorders (GLMDs) are various resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake a lack physical activity may contribute oxidative stress (OxS) systemic inflammation. This study aimed review the connection between GLMD, OxS, metainflammation, onset CRVD. GLMD is due causing dysfunction synthesis, breakdown, absorption glucose lipids body, excessive ectopic accumulation these molecules. mainly neuroendocrine dysregulation, insulin resistance, metainflammation. many inflammatory markers defense cells play vital role related tissues organs, such as blood vessels, pancreatic islets, liver, muscle, kidneys, adipocytes, promoting lesions that affect interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, sphingosine-1-phosphate (S1P) crucial since they glucolipid metabolism. The consequences this system organ damage morbidity mortality.
Language: Английский
Citations
23
Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(5), P. e202302453 - e202302453
Published: Feb. 22, 2024
The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical reduce the severity COVID-19. However, continuous emergence new SARS-CoV-2 subtypes highlights need develop additional approaches that oppose viral infections. Targeting host factors support virus entry, replication, and propagation provide opportunities lower infection rates improve COVID-19 outcome. This includes cellular cholesterol, which is for spike proteins capture machinery cell entry. Once endocytosed, exit from late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, ezetimibe have revealed potential protect against pharmacological inhibition cholesterol exiting endosomes/lysosomes identified drug candidates, including antifungals, block infection. review describes multiple roles at surface endolysosomes entry drugs targeting homeostasis infectivity disease severity.
Language: Английский
Citations
9
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Aug. 21, 2023
Abstract Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein disorders patients, intravenous administration E is able to potentiate in mice. Through pull-down mass spectrometry, find CD36, a transmembrane glycoprotein, directly binds mediates hyperactivation human mouse platelets through p38 MAPK-NF-κB signaling pathway. Conversely, pharmacological blockade CD36 or notably attenuates platelet activation induced by protein. Similarly, genetic deficiency , as well inhibition mice, significantly diminishes protein-induced thrombotic events. Together, our study reveals critical role for CD36-p38 axis hyperactivity, which could serve an actionable target developing therapies against aberrant events related severity mortality COVID-19.
Language: Английский
Citations
17
Archivum Immunologiae et Therapiae Experimentalis, Journal Year: 2024, Volume and Issue: 72(1)
Published: Jan. 1, 2024
Abstract Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided framework for understanding pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow hypercoagulability. In last years, it has become apparent that immunity plays central role thrombosis, interacting classical prothrombotic mechanisms, oxidative stress vascular factors. Thrombosis amplifies inflammation, exaggerated inflammatory processes can trigger mainly due activation of leukocytes, platelets, cells. APE-related endothelium injury major immune system activation. Endothelium also key component mediating reaction relevant maintain permeability. Exaggerated right ventricular wall overload, coexisting systemic hypotension hypoxemia, result myocardial necrosis. Hypoxia, tissue factor cytokine storm are engaged thrombo-inflammatory processes. Thrombus development characterized by state caused an early extravasation leukocytes intense selectins cytokines production. Nevertheless, DVT well described, little known about potential chemokine cellular differences between develops detaches lodges circulation being cause APE. There paucity data considering artery during episode embolism. The main aim this review summarize knowledge phase experimental models.
Language: Английский
Citations
7
Rheumatology Science and Practice, Journal Year: 2024, Volume and Issue: 62(1), P. 32 - 54
Published: Feb. 29, 2024
The pandemic of coronavirus disease 2019 (COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has drawn attention new clinical and fundamental problems in immunopathology human diseases associated with virus-induced autoimmunity autoinflammation. provision that “the experience gained rheumatology process studying pathogenetic mechanisms pharmacotherapy immunoinflammatory rheumatic as most common severe forms autoimmune autoinflammatory pathology humans will be demand for deciphering nature pathological processes underlying COVID-19 developing approaches effective pharmacotherapy” was confirmed numerous studies conducted over next 3 years midst pandemic. main focus on a critical analysis data regarding role inflammation, which basis pathogenesis immune-mediated context COVID-19.
Language: Английский
Citations
7
The Journal of Immunology, Journal Year: 2024, Volume and Issue: 213(4), P. 407 - 417
Published: Aug. 5, 2024
Abstract The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis secretion of mature, bioactive forms IL-1β IL-18. is essential in genesis progression infectious illnesses. Herein, we provide a comprehensive review diseases, focusing on its two-sided effects. As an part host defense with protective impact, abnormal activation, however, result systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence small molecules, biologics, phytochemicals acting reviewed. We believe that helps us understand pathological mechanism different stages diseases inhibitors targeting will become new valuable research direction for treatment diseases.
Language: Английский
Citations
7
European Heart Journal, Journal Year: 2023, Volume and Issue: 44(35), P. 3303 - 3304
Published: Aug. 2, 2023
The US Food and Drug Administration (FDA) has recently approved colchicine to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, cardiovascular (CV) death in adult patients with established atherosclerotic disease or multiple factors for CV disease.Colchicine was used centuries cure gouty arthritis more acute recurrent pericarditis auto-inflammatory diseases due its wide anti-inflammatory action depending on (i) interference microtubule functions; (ii) impairment neutrophil chemotaxis, mobilization, recruitment; (iii) neutrophil-platelet interplay; (iv) indirect blockade NACHT, leucine-rich repeat, pyrin domaincontaining protein 3 (NLRP3) inflammasome oligomerization through interferences microtubules 1 (Figure 1).Once depicted as a mere accumulation lipids within vessel wall, atherosclerosis is now considered an inflammatory disease. 2 Accumulation pro-inflammatory lipoproteins lumen arteries causes endothelial dysfunction followed by activation NLRP3 production inflammasome-dependent cytokines, interleukin-1β (IL-1β), IL-18. 3These events are responsible sustaining dysfunction, impairing vasodilation, homing leukocytes, promotion oxidative stress, outward remodelling artery wall.Interleukin-1β locally stimulates coagulation platelet activation, thus promoting plaque rupture thrombosis, systemically induces IL-6 production, that increase pro-coagulant events, fuels vicious cycle increasing events. 3Modulation inflammasome/IL-1β axis then resulted appealing therapeutic target burden disease.While statins showed possess cholesterol-lowering properties effects, reducing 'residual cholesterol risk', portion these reached levels low-density lipoprotein but were found be still at risk'. 4In seminal Canakinumab ANtiinflammatory Thrombosis Outcome Study (CANTOS) trial canakinumab-a monoclonal antibody blocking IL-1β-reduced prior MI who aggressively treated evidence systemic inflammation (high-sensitivity C-reactive ≥ mg/L), irrespective any impact lipids. 5Accordingly, it been shown among
Language: Английский
Citations
15
Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2024, Volume and Issue: 44(12), P. 2371 - 2395
Published: Oct. 10, 2024
Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents cardiovascular risk prognostic factor but also plays key pathogenic roles in CVD development progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges safety efficacy profile drugs; (3) difficulties identifying optimal patient candidates responders therapeutics, as well windows. Randomized controlled trials demonstrated safety/efficacy canakinumab colchicine secondary prevention, providing confirmation for involvement specific inflammatory pathway (NLRP3 [NACHT, LRR, PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) atherosclerotic CVD. Colchicine was recently approved by US Food Drug Administration this indication. Diverse drugs targeting distinct pathways are used management other CVDs including myocarditis pericarditis. Ongoing research efforts directed implementing strategies growing number through repurposing available novel compounds, which herein concisely discussed. This review summarizes main characteristics findings completed upcoming randomized directly discusses future perspectives exciting constantly expanding landscape cardioimmunology.
Language: Английский
Citations
5
World Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 20(4), P. 307 - 324
Published: Feb. 6, 2024
Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise the pediatric population with debilitating systemic impacts can be fatal at times, meriting further attention from clinicians. Meanwhile, intricate interactions between pathogen virulence factors host defense mechanisms are believed play indispensable roles COVID-19 pathophysiology but remain incompletely understood.
Language: Английский
Citations
4
Current Cardiology Reports, Journal Year: 2025, Volume and Issue: 27(1)
Published: Jan. 8, 2025
Abstract Purposeof the Review In this review article, we aim to provide an overview of pathophysiology, clinical features, therapeutic management and prognosis patients affected by Multisystemic inflammatory syndrome (MIS) with cardiac involvement, focusing on myocarditis pericarditis. Recent Findings MIS is a multiorgan hyperinflammatory condition due cytokine storm following (within 4–12 weeks) SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection. First described in children, it also affects young adults without comorbidities, predominantly males highly heterogeneous manifestations, including involvement. Summary Pericardial myocardial involvement are prevalent among leading different manifestations arrhythmias, acute heart failure cardiogenic shock that significantly affect patient's prognosis. The heterogeneity its features significant overlap other diseases make diagnosis particularly challenging. Moreover, evidence efficacy pharmacological treatments targeting response scarce, as well data long-term
Language: Английский
Citations
0