BACKGROUND: Adiposity is associated with high serum levels of adipokines and chemokines which are possibly implicated in a co-existence of obesity and asthma.OBJECTIVES: Elucidate the possible roles of leptin, interleukin (IL)-4, IL-5 and IL-21 in linking obesity with childhood asthma.DESIGN: Cross-sectional, analytical.SETTING: Population of schoolchildren in a small Saudi city.SUBJECTS AND METHODS: The study included a representative sample of Saudi schoolchildren grouped as obese asthmatics, non-obese asthmatics, or obese nonasthmatics, with nonobese nonasthmatics as a control group. An asthma control test was done for the asthmatic groups.MAIN OUTCOME MEASURES: Serum levels of leptin, IL-4, IL-5, and IL-21.SAMPLE SIZE: 345 male schoolchildren with a mean (SD) age of 13.0 (2.3) years.RESULTS: Median serum leptin concentrations in obese asthmatics were significantly higher than in nonobese asthmatics (P<.001). Uncontrolled asthmatics also had significantly higher leptin levels than controlled asthmatic children (P<.002). Leptin levels were weakly but significantly correlated with the cytokines IL-4, IL-5, and IL-21.CONCLUSIONS: Leptin may contribute to a link between obesity and childhood asthma. Differences in IL-21 levels between nonobese and obese asthmatics suggest that the co-existence of asthma and obesity increased IL-21 levels. Leptin plus some proinflammatory cytokines especially IL-21 may be potential predictors for asthma control in children.LIMITATIONS: Blood sampling at different stages of asthma might influence cytokine expression.CONFLICT OF INTEREST: None.
Ghrelin is a peptide hormone with direct or indirect effects on obesity and asthma. More data are required to understand the effect of ghrelin on the control and pathogenesis of these diseases. The aim of this study was to evaluate ghrelin levels in selected groups of children to identify the association between serum ghrelin, obesity, and the severity of asthma. The study included 401 school children selected from the Najran area and grouped into non-obese asthmatics, obese asthmatics, obese non-asthmatics and controls (non-obese non-asthmatics). Blood levels of ghrelin, interleukin (IL)-4, IL-5 and IL-21 were determined by ELISA. The mean ghrelin values were insignificantly increased in obese children compared with non-obese children. The highest blood ghrelin values were in the non-obese asthmatic group. Serum ghrelin, IL-4 and IL-21 levels were significantly increased in asthmatic children compared with non-asthmatic children (p < 0.05), and there were significant positive correlations between ghrelin and IL-4, IL-5, and IL-21 in asthmatic children. Furthermore, ghrelin, IL-4, and IL-21 levels were significantly higher in uncontrolled asthmatics compared with controlled-asthmatic children (p < 0.05). Asthma was the only significant risk factor for high ghrelin values. This study provides evidence supporting the anti-inflammatory role of ghrelin in the pathogenesis of asthma. Asthma might be considered as an important determinant of high ghrelin values in children.
Background: The primary carrier of bile acids in humans is the bile salt export pump (BSEP). which are crucial for the digestion and absorption of fat. Type 2 progressive familial intrahepatic cholestasis (PFIC-2), which is brought on when BSEP is suppressed and causes a decrease in bile flow and a buildup of cytotoxic bile salts in the liver, is one of the main causes of cholestasis in Saudi Arabia. Elucidate the inhibitory potential with minimal or no adverse effects.Methods: The structure (6LR0) was downloaded from the PDB. Protein active sites were anticipated because these are pockets where ligands can bind and perform reactions to treat an infection. The PubChem zinc and mpd3 databases were used to get the ligands' structures. Molecular operating environment (MOE) was utilized to perform molecular docking of 1600 phytochemicals against BSEP. LigX was used to observe the docking hits for interaction analysis. Results: identification of 4 potential candidates for binding to the BSEP active site. then, Protox II-was used to forecast toxicity for the selected hits. Molecular dynamics simulations were also used to assess the binding complex's stability in water for 100 nanoseconds. The strong binding affinity of high-ranked drugs was predicted by our molecular docking and simulation.Conclusions: This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the BSEP. The aim of this research is to identify novel -BSEP drug targets, and in future in vitro and in vivo research could prove its clinical efficiency.
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