Pocket Switched Networks(PSN)represent a particular remittent network for direct communication between the handheld mobile devices.Compared to traditional networks,there is no stable topology structure for PSN where t...Pocket Switched Networks(PSN)represent a particular remittent network for direct communication between the handheld mobile devices.Compared to traditional networks,there is no stable topology structure for PSN where the nodes observe the mobility model of human society.It is a kind of Delay Tolerant Networks(DTNs)that gives a description to circulate information among the network nodes by the way of taking the benefit of transferring nodes from one area to another.Considering its inception,there are several schemes for message routing in the infrastructure-less environment in which human mobility is only the best manner to exchange information.For routing messages,PSN uses different techniques such asDistributed Expectation-Based Spatio-Temporal(DEBT)Epidemic(DEBTE),DEBT Cluster(DEBTC),and DEBT Tree(DEBTT).Understanding on how the network environment is affected for these routing strategies are the main motivation of this research.In this paper,we have investigated the impact of network nodes,the message copies per transmission,and the overall carrying out of these routing protocols.ONE simulator was used to analyze those techniques on the basis of delivery,overhead,and latency.The result of this task demonstrates that for a particular simulation setting,DEBTE is the best PSN routing technique among all,against DEBTC and DEBTT.展开更多
Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and live...Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many patients.Recently,we have shown that combining a gut-restricted apical sodium-bile acid transporter(ASBT)inhibitor GSK2330672(GSK)with adeno-associated virus(AAV)-mediated liver fibroblast growth factor 15(FGF15)overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat,cholesterol,and fructose(HFCFr)diet-induced NASH mouse model.The beneficial effects of the com-bined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid absorption.The aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid(OCA),which induces endogenous FGF15 and inhibits hepatic bile acid synthesis,can achieve similar anti-NASH effect as the GSKþAAV-FGF15 co-treatment in HFCFr-diet-fed mice.Materials and methods:Male C57BL/6J mice were fed HFCFr diet to induce NASH and liver fibrosis.The effect of GSK,OCA,and GSKþOCA treatments on NASH development was compared and contrasted among all groups.Results:Findings from this study showed that the GSKþOCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment period.Neither single treatment nor the GSKþOCA co-treatment reduce hepatic steatosis,but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar magnitude.The GSKþOCA co-treatment caused a higher degree of total bile acid pool reduction(~55%)than either GSK or OCA treatment alone.However,such bile acid pool reduction was insufficient to cause increased fecal lipid loss.The GSKþOCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression.GSK did not reduce gallbladder OCA amount in the GSKþOCA group compared to the OCA group,suggesting that ASBT inhibition does not reduce hepatic OCA distribution.Conclusions:Unlike the GSKþAAV-FGF15 co-treatment,the GSKþOCA co-treatment does not provide improved efficacy against NASH and liver fibrosis than either single treatment in mice.The lack of synergistic effect may be partly attributed to the moderate reduction of total bile acid pool and the lack of high level of FGF15 exposure as seen in the GSKþAAV-FGF15 co-treatment.展开更多
基金UPNM Grant J0117-UPNM/2016/GPJP/5/ICT/2.The authors fully acknowledged Ministry of Higher Education(MOHE)and National Defence University of Malaysia for the approved fund which makes this important research viable and effective.The authors also would like to thank University Grant Commission of Bangladesh,Comilla University for the financial support.
文摘Pocket Switched Networks(PSN)represent a particular remittent network for direct communication between the handheld mobile devices.Compared to traditional networks,there is no stable topology structure for PSN where the nodes observe the mobility model of human society.It is a kind of Delay Tolerant Networks(DTNs)that gives a description to circulate information among the network nodes by the way of taking the benefit of transferring nodes from one area to another.Considering its inception,there are several schemes for message routing in the infrastructure-less environment in which human mobility is only the best manner to exchange information.For routing messages,PSN uses different techniques such asDistributed Expectation-Based Spatio-Temporal(DEBT)Epidemic(DEBTE),DEBT Cluster(DEBTC),and DEBT Tree(DEBTT).Understanding on how the network environment is affected for these routing strategies are the main motivation of this research.In this paper,we have investigated the impact of network nodes,the message copies per transmission,and the overall carrying out of these routing protocols.ONE simulator was used to analyze those techniques on the basis of delivery,overhead,and latency.The result of this task demonstrates that for a particular simulation setting,DEBTE is the best PSN routing technique among all,against DEBTC and DEBTT.
文摘Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many patients.Recently,we have shown that combining a gut-restricted apical sodium-bile acid transporter(ASBT)inhibitor GSK2330672(GSK)with adeno-associated virus(AAV)-mediated liver fibroblast growth factor 15(FGF15)overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat,cholesterol,and fructose(HFCFr)diet-induced NASH mouse model.The beneficial effects of the com-bined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid absorption.The aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid(OCA),which induces endogenous FGF15 and inhibits hepatic bile acid synthesis,can achieve similar anti-NASH effect as the GSKþAAV-FGF15 co-treatment in HFCFr-diet-fed mice.Materials and methods:Male C57BL/6J mice were fed HFCFr diet to induce NASH and liver fibrosis.The effect of GSK,OCA,and GSKþOCA treatments on NASH development was compared and contrasted among all groups.Results:Findings from this study showed that the GSKþOCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment period.Neither single treatment nor the GSKþOCA co-treatment reduce hepatic steatosis,but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar magnitude.The GSKþOCA co-treatment caused a higher degree of total bile acid pool reduction(~55%)than either GSK or OCA treatment alone.However,such bile acid pool reduction was insufficient to cause increased fecal lipid loss.The GSKþOCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression.GSK did not reduce gallbladder OCA amount in the GSKþOCA group compared to the OCA group,suggesting that ASBT inhibition does not reduce hepatic OCA distribution.Conclusions:Unlike the GSKþAAV-FGF15 co-treatment,the GSKþOCA co-treatment does not provide improved efficacy against NASH and liver fibrosis than either single treatment in mice.The lack of synergistic effect may be partly attributed to the moderate reduction of total bile acid pool and the lack of high level of FGF15 exposure as seen in the GSKþAAV-FGF15 co-treatment.
