Mossmcpherson2197

According to the "obesity paradox", adults with obesity have a survival advantage following acute coronary syndrome, compared with those without obesity. Previous studies focused on peripheral obesity and whether this advantage is conferred by central obesity is unknown. The objective of this study was to describe the association of peripheral and central obesity indices with risk of in-hospital and 1-year mortality following acute coronary syndrome (ACS).

Gulf COAST is a prospective ACS registry that enrolled 4044 patients age ≥18 years from January 2012 through January 2013, across 29 hospitals in four Middle Eastern countries. Associations of indices of peripheral obesity (body-mass index, [BMI]) and central obesity (waist circumference [WC] and waist-to-height ratio [WHtR]) with mortality following ACS were analyzed in logistic regression models (odds ratio, 95% CI) with and without adjustment for Global Registry of Acute Coronary Events risk score.

Of 3882 patients analyzed (mean age 60 years; 33.3ng ACS depends on the obesity index and follow-up time. Obesity indices may aid in risk stratification of mortality following ACS.

HSG4112 is a clinical-stage drug candidate for the treatment of obesity. Here, we report its discovery and preclinical efficacy.

In high-fat diet (HFD)-induced obese male C57BL/6J mice, we tested the weight loss effect of synthetic compounds derived from a structure-activity relationship (SAR) study of glabridin, a natural compound known to reduce body weight and influence energy homeostasis. After selecting HSG4112 as our optimized compound from this discovery method, we characterized its pharmacological effects on parameters related to obesity through in vivo metabolic and biochemical measurements, histology and gene expression analysis, and indirect calorimetry.

Through the SAR study, we identified four novel components of glabridin pertinent for its anti-obesity activity, and found that HSG4112, an optimized structural analog of glabridin, markedly supersedes glabridin in weight reduction efficacy and chemical stability. Six-week administration of HSG4112 to HFD-induced obese mice led to dose-dependent normalization of obesity-related parameters, including body weight, muscle and adipose tissue weight, adipocyte size, and serum leptin/insulin/glucose levels. The weight reduction induced by HSG4112 was partially mediated by decreased food intake and mainly mediated by increased energy expenditure, with no change in physical activity. Accordingly, the pattern of transcriptional changes was aligned with increased energy expenditure in the liver and muscles. Following significant body weight reduction, robust amelioration of histopathology and blood markers of fatty liver were also observed.

Our study demonstrates the key chemical components of glabridin pertinent to its weight loss effects and suggests HSG4112 as a promising novel drug candidate for the pharmacological treatment of obesity.

Our study demonstrates the key chemical components of glabridin pertinent to its weight loss effects and suggests HSG4112 as a promising novel drug candidate for the pharmacological treatment of obesity.Accurate identification of both abundant and rare proteins hinges on the development of single-protein sensing methods. Given the immense variation in protein expression levels in a cell, separation of proteins by weight would improve protein classification strategies. Upstream separation facilitates sample binning into smaller groups while also preventing sensor overflow, as may be caused by highly abundant proteins in cell lysates or clinical samples. Here, we scale a bulk analysis method for protein separation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), to the single-molecule level using single-photon sensitive widefield imaging. Single-molecule sensing of the electrokinetically moving proteins is achieved by in situ polymerization of the PAGE in a low-profile fluidic channel having a depth of only ~ 0.6 µm. The polyacrylamide gel restricts the Brownian kinetics of the proteins, while the low-profile channel ensures that they remain in focus during imaging, allowing video-rate monitoring of single-protein migration. Calibration of the device involves separating a set of Atto647N-covalently labeled recombinant proteins in the size range of 14-70 kDa, yielding an exponential dependence of the proteins' molecular weights on the measured mobilities, as expected. Subsequently, we demonstrate the ability of our fluidic device to separate and image thousands of proteins directly extracted from a human cancer cell line. selleck chemicals llc Using single-particle image analysis methods, we created detailed profiles of the separation kinetics of lysine and cysteine -labeled proteins. Downstream coupling of the device to single-protein identification sensors may provide superior protein classification and improve our ability to analyze complex biological and medical protein samples.An excessive immune response during coronavirus disease (COVID-19) can induce cytokine release syndrome (CRS), which is associated with life-threatening complications and disease progression. This retrospective study evaluated the clinical characteristics of severe CRS (sCRS, grade 3-4) induced by severe COVID-19 (40 patients) or chimeric antigen receptor T-cell (CAR-T) therapy as a comparator (41 patients). Grade 4 CRS was significantly more common in the COVID-19 group (15/40 (35.7%) vs. 5/41 (12.2%), P = 0.008). The CAR-T group had more dramatic increase in cytokines, including IL-2, IL-6, IL-10, and IFN-γ. Interestingly, COVID-19 group had significantly higher levels for TNF-α (31.1 pg/ml (16.1-70.0) vs. 3.3 (1.8-9.6), P  less then  0.001) and lg viral loads were correlated with lg IL-6 (R2 = 0.101; P  less then  0.001) and lg IL-10 (R2 = 0.105; P  less then  0.001). The independent risk factor for COVID-19-related sCRS was hypertension history (OR 4.876, 95% CI 2.038-11.668; P  less then  0.001). Our study demonstrated that there were similar processes but different intensity of inflammatory responses of sCRS in COVID-19 and CAR-T group. The diagnose and management of severe COVID-19-related sCRS can learn lessons from treatment of sCRS induced by CAR-T therapy.