ABSTRACT
Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.
ABSTRACT
BACKGROUND: Obesity is a common disease among children, often accompanied by a lot of metabolic disease. Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of obesity among children and adolescents. Asprosin has been identified as a new adipokine that is closely associated with hepatic glucose metabolism. However, few data on asprosin in obese children with NAFLD are available. The present study focuses on the relationship between serum asprosin level and NAFLD in children with obesity. METHODS: A total of 110 subjects (71 boys and 39 girls aged 6-18 years) were recruited from the Second Affiliated Hospital of Xi'an Jiaotong University: 36 obese children with NAFLD, 39 obese children without NAFLD and 35 lean controls. Anthropometric parameters and biochemical data were measured, and the concentrations of asprosin were detected by ELISA. RESULTS: The levels of serum asprosin were significantly higher in obese children, particularly those with NAFLD and were positively correlated with body mass index, waist to height ratio, fasting blood glucose, alanine aminotransferase and tumor necrosis factor-alpha. Furthermore, asprosin was independently associated with NAFLD in binary logistic regression analysis. CONCLUSION: Serum asprosin levels were elevated in obese children, especially in those with NAFLD, and were involved in the pathogenesis of NAFLD in children with obesity.
Subject(s)
Insulin Resistance , Non-alcoholic Fatty Liver Disease , Pediatric Obesity , Adolescent , Anthropometry , Body Mass Index , Child , Female , Fibrillin-1 , Humans , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Pediatric Obesity/complications , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiologyABSTRACT
OBJECTIVE: The study was conducted to evaluate the stability of commercial coated lipase (CT-LIP) in vitro. METHODS: The capsules were tested under different conditions with a range of temperature, pH, dry heat treatment and steaming treatment, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) in this work, respectively. Free lipase (uncoated lipase, UC-LIP) was the control group. Lipase relative activities measured in various treatments were used as a reference frame to characterize the stability. RESULTS: The lipase activities were decreased with increasing temperatures (p<0.05), and there was a markedly decline (p<0.01) in lipase comparative activities of UC-LIP at 80°C compared with CT-LIP group. Higher relative activities of lipase were observed in CT-LIP group compared with the free one under acidic ambient (pH 3 to 7) and an alkaline medium (pH 8 to 12). Residual lipase activities of CT-LIP group were increased (p<0.05) by 5.67% and 35.60% in dry heat and hydrothermal treatments, respectively. The lipase relative activity profile of CT-LIP was raised at first and dropped subsequently (p<0.05) compared with constantly reduced tendency of UC-LIP exposed to both SGF and SIF. CONCLUSION: The results suggest that the CT-LIP possesses relatively higher stability in comparison with the UC-LIP in vitro. The CT-LIP could retain the potential property to provide sustained release of lipase and thus improved its bioavailability in the gastrointestinal tract.
