AIM： To investigate the molecular mechanism and functional consequences of heme oxygenase-1 （HO-1） activation by lansoprazole in endothelial cells and macrophages. METHODS： Expression of HO-1 mRNA was analyzed by ...AIM： To investigate the molecular mechanism and functional consequences of heme oxygenase-1 （HO-1） activation by lansoprazole in endothelial cells and macrophages. METHODS： Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species （ROS） formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH- mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity.CONCLUSION： Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002.展开更多
In this paper, we investigate a new model with a generalized feedback mechanism in weighted networks. Compare to previous models, we consider the initiative response of people and the important impact of nodes with di...In this paper, we investigate a new model with a generalized feedback mechanism in weighted networks. Compare to previous models, we consider the initiative response of people and the important impact of nodes with different edges on transmission rate as epidemics prevail. Furthermore, by constructing Lyapunov function, we prove that the disease-free equilibrium E^0 is globally asymptotically stable as the epidemic threshold R^＊〈 1. When R^＊ 〉 1, we obtain the permanence of epidemic and the local stability of endemic equilibrium E＊. Finally, one can find a good agreement between numerical simulations and our analytical results.展开更多
基金Supported by The German Academic Exchange Program(DAAD,S.S.G.)
文摘AIM： To investigate the molecular mechanism and functional consequences of heme oxygenase-1 （HO-1） activation by lansoprazole in endothelial cells and macrophages. METHODS： Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species （ROS） formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH- mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity.CONCLUSION： Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002.
基金This work is supported by the National Natural Science Foundation of China under Grant 61174039. The authors would like to thank the editor and the reviewers for their constructive comments and suggestions to improve the quality of this paper.
文摘In this paper, we investigate a new model with a generalized feedback mechanism in weighted networks. Compare to previous models, we consider the initiative response of people and the important impact of nodes with different edges on transmission rate as epidemics prevail. Furthermore, by constructing Lyapunov function, we prove that the disease-free equilibrium E^0 is globally asymptotically stable as the epidemic threshold R^＊〈 1. When R^＊ 〉 1, we obtain the permanence of epidemic and the local stability of endemic equilibrium E＊. Finally, one can find a good agreement between numerical simulations and our analytical results.
