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.
View Article and Find Full Text PDFCoagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma coagulation factors and their inhibitors that, in addition to thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both hypercoagulability and bleeding disorders due to a pathologic balance of pro- and anticoagulant plasma factors.
View Article and Find Full Text PDFNeutrophil extracellular traps (NETs) and polyphosphates (polyP) have been recognized as procoagulant polyanions. This review summarizes the activities and regulation of the two procoagulant mediators and compares their functions. NETs are composed of DNA which like polyP is built of phosphate units linked by high-energy phosphoanhydride bonds.
View Article and Find Full Text PDFPlatelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia.
View Article and Find Full Text PDFInt J Appl Basic Med Res
January 2017
Background: (PN) is well known for its cytotoxic and pharmacological benefits. However, there is minimal documented evidence about its cytotoxic efficacy against colorectal carcinoma. We therefore sought to procure a precisely quantitative and qualitative result, pertaining the efficacy of an ethanolic extract of PN (EEPN) against colorectal carcinoma.
View Article and Find Full Text PDFBackground: Stress cardiomyopathy (SCM) is a newly described reversible cardiomyopathy of largely unclear etiology. We studied SCM in a large cohort to gain further insights.
Methods: We retrospectively identified 114 cases of SCM from among 12,150 consecutive North American patients diagnosed as Troponin-positive acute coronary syndrome, from January 2000 through December 2007, at two 24-h coronary angioplasty-capable centers.
Purpose: Although angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with systolic heart failure, prior studies suggest that elderly cohorts are less likely to receive such therapy. The purpose of this study was to determine the age dependence of adherence to guideline-based medical care in hospitalized heart failure patients.
Methods: We performed a multicenter observational cohort study including 613 patients admitted to participating hospitals with a primary diagnosis of heart failure with ejection fraction < or =40%.