Tspan18 is a novel regulator of thrombo-inflammation

AbstractThe interplay between thrombosis and inflammation, termed thrombo-inflammation, causes acute organ damage in diseases such as ischaemic stroke and venous thrombosis. We have recently identified tetraspanin Tspan18 as a novel regulator of thrombo-inflammation. The tetraspanins are a family of 33 membrane proteins in humans that regulate the trafficking, clustering, and membrane diffusion of specific partner proteins. Tspan18 partners with the store-operated Ca2+ entry channel Orai1 on endothelial cells. Orai1 appears to be expressed in all cells and is critical in health and disease. Orai1 mutations cause human immunodeficiency, resulting in chronic and often lethal infections, while Orai1-knockout mice die at around the time of birth. Orai1 is a promising drug target in autoimmune and inflammatory diseases, and Orai1 inhibitors are in clinical trials. The focus of this review is our work on Tspan18 and Orai1 in Tspan18-knockout mice and Tspan18-knockdown primary human endothelial cells. Orai1 trafficking to the cell surface is partially impaired in the absence of Tspan18, resulting in impaired Ca2+ signaling and impaired release of the thrombo-inflammatory mediator von Willebrand factor following endothelial stimulation. As a consequence, Tspan18-knockout mice are protected in ischemia –reperfusion and deep vein thrombosis models. We provide new evidence that Tspan18 is relatively highly expressed in endothelial cells, through the analysis of publicly available ...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research

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CONCLUSIONS: The GXT provided only a peak VO2 but not the VO2max. Consequently, the real VO2max and PPO could be provided by only VP administrations. This is likely to result from the lower Qc and SV responses observed from a prolonged incremental test protocol when compared to short bouts of constant work rate trials. PMID: 32639117 [PubMed - as supplied by publisher]
Source: Journal of Sports Medicine and Physical Fitness - Category: Sports Medicine Tags: J Sports Med Phys Fitness Source Type: research
CONCLUSIONS: PulseRider-assisted coiling for treatment of patients with wide-necked aneurysm reached 90% adequate occlusion rate that rises up to 91% at sixth month with 5% complication rate. PMID: 32635777 [PubMed - as supplied by publisher]
Source: Interventional Neuroradiology - Category: Radiology Tags: Interv Neuroradiol Source Type: research
Abstract Pemphigus is a group of autoimmune bullous skin diseases that result in significant morbidity. As for other multifactorial autoimmune disorders, environmental factors may trigger the disease in genetically susceptible individuals. The goals of this review are to summarize the state of knowledge about the genetic variation that may affect the susceptibility and pathogenesis of pemphigus vulgaris and pemphigus foliaceus - both the endemic and the sporadic forms -, to compare and discuss the possible meaning of the associations reported, and to propose recommendations for new research initiatives. Understand...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Genet Mol Biol Source Type: research
Publication date: Available online 8 July 2020Source: The American Journal of SurgeryAuthor(s): Madeline B. Torres, Heather A. Kendall, Andrew Kerwin, Ziad Awad, Joseph Tepas, Marie Crandall, Jin Ra
Source: The American Journal of Surgery - Category: Surgery Source Type: research
Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractPurposeChronic kidney disease (CKD) associates with inflammatory and prothrombotic phenotypes, resulting in higher cardiovascular risk. Factor Xa displays functions beyond coagulation, exhibiting proinflammatory effects. The aim of the present study was to investigate whether a direct FXa inhibitor protects from the endothelial dysfunction (ED) caused by uremia.MethodsMacro (HUVEC) and microvascular (HMEC) endothelial cells (ECs) were exposed to serum from uremic patients or healthy donors, in absence and presence of apixaban (60 ng/ml). We evaluated changes in surface VCAM-1 and ICAM-1, intracellular eNOS, reactiv...
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
Publication date: Available online 8 July 2020Source: International Journal of Nursing SciencesAuthor(s): Nursiswati Nursiswati, Ruud JG. Halfens, Christa Lohrmann
Source: International Journal of Nursing Sciences - Category: Nursing Source Type: research
Neurological manifestations include inflammatory CNS syndromes, encephalopathies, ischemic stroke
Source: The Doctors Lounge - Psychiatry - Category: Psychiatry Tags: Infections, Neurology, Pathology, Psychiatry, Radiology, Critical Care, Emergency Medicine, Journal, Source Type: news
CONCLUSIONS: Detection of serum levels of CCAT2 and miRNA-216b could be applied for predicting the rupture of carotid atherosclerotic plaques. They may be potential biomarkers predicting ischemic stroke. PMID: 32633397 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Conditions:   Traumatic Brain Injury;   Cerebral Stroke Intervention:   Device: Exoskeleton Rehabilitation Sponsor:   Doctors Hospital at Renaissance Active, not recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Allergy & Immunology | Autoimmune Disease | Clinical Trials | Ischemic Stroke | Microbiology | Stroke | Thrombosis | von Willebrand Disease