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Oxymatrine Attenuates Osteoclastogenesis via Modulation involving ROS-Mediated SREBP2 Signaling and also Counteracts Ovariectomy-Induced Weak bones.
Salvionolic acid B, a CD36 inhibitor and a CD36 inhibitor antibody reduced oxLDL-induced MΦMP by 67% and 60%, respectively. Caspase 3/7 inhibition reduced MΦMP release by 52% (P less then 0.01) and caspase 3/7 activation increased MΦMP production by 208% (P less then 0.01). Mevastatin pretreatment (10 µM) decreased oxLDL-induced caspase 3/7 activation and attenuated oxLDL-stimulated MΦMP production and tissue factor content by 60% (P less then 0.01) and 43% (P less then 0.05), respectively. Conclusions OxLDL induces the production of prothrombotic microparticles in macrophages. This process depends on caspases 3 and 7 and CD36 and is inhibited by mevastatin pretreatment. These findings link atherogenic signaling pathways, inflammation, and plaque thrombogenicity and identify a novel potential mechanism for antithrombotic effects of statins independent of LDL lowering.Background In adults with heart failure, elevated heart rate is associated with lower survival. We determined whether an elevated heart rate was associated with an increased risk of death or heart transplant in children with dilated cardiomyopathy. Methods and Results The study is an analysis of the Pediatric Cardiomyopathy Registry and includes baseline data, annual follow-up, and censoring events (transplant or death) in 557 children (51% male, median age 1.8 years) with dilated cardiomyopathy diagnosed between 1994 and 2011. An elevated heart rate was defined as 2 or more SDs above the mean heart rate of children, adjusted for age. The primary outcomes were heart transplant and death. Heart rate was elevated in 192 children (34%), who were older (median age, 2.3 versus 0.9 years; P less then 0.001), more likely to have heart failure symptoms (83% versus 67%; P less then 0.001), had worse ventricular function (median fractional shortening z score, -9.7 versus -9.1; P=0.02), and were more often receiving anticongestive therapies (96% versus 86%; P less then 0.001) than were children with a normal heart rate. Controlling for age, ventricular function, and cardiac medications, an elevated heart rate was independently associated with death (adjusted hazard ratio [HR] 2.6; P less then 0.001) and with death or transplant (adjusted HR 1.5; P=0.01). Conclusions In children with dilated cardiomyopathy, elevated heart rate was associated with an increased risk of death and cardiac transplant. Further study is warranted into the association of elevated heart rate and disease severity in children with dilated cardiomyopathy and as a potential target of therapy.Background Recent studies have reported the association between pericoronary inflammation assessed by pericoronary adipose tissue attenuation (PCATA) on computed tomography angiography and worse outcomes in patients with coronary artery disease. We investigated the determinants predicting increased PCATA in patients with known or suspected coronary artery disease. Methods and Results A total of 540 patients who underwent computed tomography angiography and invasive coronary angiography were studied. Mean computed tomography attenuation values of PCAT (-190 to -30 Hounsfield units) (PCATA) were assessed at the proximal 40-mm segments of all 3 major coronary arteries by crude analysis. Univariable and multivariable analyses were performed to determine the predictors of increased PCATA surrounding the proximal right coronary artery. Mean right coronary artery-PCATA was -72.22±8.47 Hounsfield units and the average of 3-vessel PCATA was -70.24±6.60 Hounsfield units. Multivariable linear regression analysis revealeaphy angiography.BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P less then 0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (P less then 0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P less then 0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.Background Cardiac features diverge in Asians; however, it is not known how these differences relate to embolic stroke of unknown source (ESUS) in Southeast Asian and Eastern Mediterranean regions. Methods and Results A retrospective analysis of prospectively collected acute ischemic stroke data from 2014 to 2018 was performed. Selleckchem Pimasertib Stroke subtypes were noncardioembolic stroke (large-vessel and small-vessel disease; n=1348), cardioembolic stroke (n=532), and ESUS (n=656). Subtypes were compared by demographic, clinical, and echocardiographic factors. In multivariate logistic regression, patients with ESUS in comparison with noncardioembolic stroke were twice as likely to have left ventricular diastolic dysfunction (P=0.001), 3 times the odds of global hypokinesia (P=0.001), and >7 times the odds of left ventricular wall motion abnormalities (P=0.001). In the second model comparing ESUS with cardioembolic stroke, patients with ESUS were 3 times more likely to have left ventricular wall motion abnormalities (P=0.001) and 1.
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