Neutrophils are peripheral blood-circulating leukocytes that play a pivotal role in host defense against bacterial pathogens which upon activation, they release web-like chromatin structures called neutrophil extracellular traps (NETs). Here, we analyzed and compared the importance of myeloid differentiation factor 88 (MYD88), peptidyl arginine deiminase 4 (PAD4), and gasdermin D (GSDMD) for NET formation in vivo following sepsis and neutrophilia challenge. Injection of lipopolysaccharide (LPS)/E.
View Article and Find Full Text PDFObjectives: Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4 T cells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
January 2022
The plasma protein factor XII (FXII) is the liver-derived zymogen of the serine protease FXIIa that initiates an array of proteolytic cascades. Zymogen activation, enzymatic FXIIa activity and functions are regulated by interactions with cell receptors, negatively charged surfaces, other serine proteases, and serpin inhibitors, which bind to distinct protein domains and regions in FXII(a). FXII exerts mitogenic activity, while FXIIa initiates the pro-inflammatory kallikrein-kinin pathway and the pro-thrombotic intrinsic coagulation pathway, respectively.
View Article and Find Full Text PDFSARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound.
View Article and Find Full Text PDFPurpose: Robotic assisted laparoscopic radical prostatectomy (RARP) is considered as standard of care for surgical management of localised prostate cancer. Procedure specific postoperative pain management (PROSPECT) guidelines are available for open radical prostatectomy. There is a lack of evidence for optimal pain management protocol in patients undergoing robotic radical prostatectomy.
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