Recently, we showed that platelet alpha-granule fibrinogen is derived entirely from endocytic uptake and not from megakaryocyte synthesis, as previously thought. In this present report, we identify the receptor that mediates endocytosis. We have found that barbourin, a unique disintegrin that is a specific antagonist of alpha IIb beta 3, inhibits the endocytic uptake of fibrinogen into alpha-granules. Continuous intravenous infusion of barbourin (200 micrograms/h) into guinea pigs blocked collagen-induced platelet aggregation as well as endocytosis of biotinylated fibrinogen into megakaryocytes; however, endocytosis of biotinylated albumin by megakaryocytes was not affected. Thus, we have shown that endocytosis of fibrinogen into megakaryocyte and platelet alpha-granules is receptor-mediated, and that alpha IIb beta 3 is the primary receptor.
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JHEP Rep
February 2025
Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain.
Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation.
Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg).
Cell Death Dis
January 2025
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Auvera Haus Grombühlstraße 12, 97080, Würzburg, Germany.
This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly.
View Article and Find Full Text PDFJ Neurol
January 2025
Department of Neurology and Neurosciences, Donostia University Hospital, Biogipuzkoa Health Research Institute, Donostia-San Sebastián, Spain.
Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.
Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.
HIV Res Clin Pract
December 2025
National Heart and Lung Institute, Imperial College London, London, UK.
Introduction: The BIC-T&T study aimed to determine the efficacy of bictegraviremtricitabine/tenofovir alafenamide (BIC/F/TAF) and darunavir/cobicistat/emtricitabinetenofovir alafenamide (DRV/c/F/TAF) at suppressing viral load in a two-arm, open-label, multi-centre, randomised trial under a UK test-and-treat setting. This sub-study aimed to evaluate potential off-target cardiovascular impact by examining platelet function.
Methods: Platelets were isolated by centrifugation of citrated blood from participants attending Chelsea and Westminster Hospital or St Mary's Hospital at Week 48 following enrolment.
Int Immunopharmacol
February 2025
Institute of Immunology and Molecular Medicine, Jining Medical University, Jining 272067, China. Electronic address:
Cucurbitacins are a class of triterpenoid compounds extracted from plants and possess various pharmacological applications. Cucurbitacin IIb (CuIIb), extracted from the medicinal plant Hemsleya amabilis (Cucurbitaceae), has served as a traditional Chinese medicine for the treatment of bacterial dysentery and intestinal inflammation. CuIIb has been shown to exhibit anti-inflammatory activity; however, the protective effect of CuIIb against concanavalin A (Con A)-induced acute liver injury (ALI) and the fundamental mechanism remain unelucidated.
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