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The Integrin Receptors: From Discovery to Structure to Medicines.
Immunol Rev
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Innate immune cells perform vital tasks in detecting, seeking, and eliminating invading pathogens, thus ensuring host survival. However, loss of function of these cells or their overactive response to tissue injury often causes serious ailments. It is, therefore, crucial to understand at a basic level how these cells function in health and disease.
View Article and Find Full Text PDFPlatelet-neutrophil aggregate formation induces NLRP3 inflammasome activation in vaccine-induced thrombotic thrombocytopenia.
J Thromb Haemost
December 2024
Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Electronic address:
Background: Although rare, vaccine-induced thrombotic thrombocytopenia (VITT) following adenoviral vector COVID-19 vaccination is a concerning and often severe adverse effect of vaccination. The generation of high antiplatelet factor 4 antibody titers promotes the formation of immune complexes capable of activating platelets and neutrophils through FcγRIIa.
Objectives: Given that platelet-leukocyte aggregate formation and inflammasome activation are common features of thromboinflammatory diseases, we aimed to evaluate if these are also features of VITT.
A single-domain antibody targeting factor XII inhibits both thrombosis and inflammation.
Nat Commun
September 2024
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Article Synopsis
- Factor XII (FXII) is crucial for activating the body's intrinsic coagulation pathway and has a previously unclear role in inflammation.
- Treating male mice with a novel antibody (Nb-Fc) that targets FXII significantly reduced arterial thrombosis without disrupting normal blood clotting.
- The study shows that inhibiting FXII can lower inflammation-related symptoms and complications during procedures like extracorporeal membrane oxygenation (ECMO), indicating its potential as a therapeutic target for thrombo-inflammatory diseases.
Development of a Clonal and High-Yield Mammalian Cell Line for the Manufacturing of a Hyperactive Human DNase I with Extended Plasma Half-Life Using PASylation Technology.
Pharmaceutics
July 2024
XL-Protein GmbH, Lise-Meitner-Str. 30, 85354 Freising, Germany.
Cumulative evidence from several pre-clinical studies suggests that restoration of plasma DNase activity in a thrombo-inflammatory state may improve clinical outcomes. Following injury, hyperactivated immune cells release large amounts of granular proteins together with DNA, which often accumulate in the surrounding environment in so-called neutrophil extracellular traps (NETs). Degradation of excess NETs by systemic DNase administration offers a promising therapeutic approach to ameliorate inflammation and dissolve intravascular clots.
View Article and Find Full Text PDFA randomised controlled trial of plasma exchange compared to standard of care in the treatment of severe COVID-19 infection (COVIPLEX).
Sci Rep
July 2024
Department of Haematology, University College London Hospitals NHS Foundation Trust and Haematology Programme-NIHR UCLH/UC BRC London, 235 Euston Road, London, NW12PG, UK.
Article Synopsis
- COVID-19 is linked to severe inflammation and blood clotting issues, leading to high mortality, prompting a study on the effects of plasma exchange (PEX) in critically ill patients.
- A phase II randomized control trial was conducted with 22 patients, where 11 received PEX, resulting in reduced pro-thrombotic markers but no significant changes in inflammatory markers or overall respiratory failure.
- Despite effectively lowering specific thrombotic markers, PEX did not improve respiratory function, reduce inflammatory responses, or decrease mortality rates within 28 days.
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