This review aims at providing synthetic information with scientific evidence on the trends in the malaria events from 1960 to 2011,with the hope that it will help policy makers to take informed decisions on public hea...This review aims at providing synthetic information with scientific evidence on the trends in the malaria events from 1960 to 2011,with the hope that it will help policy makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in both Sub-Sahara Africa and in the People’s Republic of China by highlighting the achievements,progress and challenges in research on moving malaria from epidemic status towards elimination.Our findings showed that since 1960,malaria control programmes in most countries have been disjointed and not harmonized.Interestingly,during the last decade,the causal factors of the unprecedented and substantial decline in malaria morbidity and mortality rates in most vulnerable groups in these endemic areas are multifaceted,including not only the spread of malaria and its related effects but also political and financial willingness,commitment and funding by governments and international donors.The benefits of scaling up the impact of malaria coverage interventions,improvement of health system approaches and sustained commitment of stakeholders are highlighted,although considerable efforts are still necessary in Sub-Sahara Africa.Furthermore,novel integrated control strategies aiming at moving malaria from epidemic status to control towards elimination,require solid research priorities both for sustainability of the most efficient existing tools and intervention coverage,and in gaining more insights in the understanding of the epidemiology,pathogenesis,vector dynamics,and socioeconomic aspects of the disease.In conclusion,political commitment and financial investment of stakeholders in sustaining the scaling up impact of malaria control interventions,networking between African and Chinese scientists,and their Western partners are urgently needed in upholding the recent gains,and in translating lessons learnt from the Chinese malaria control achievements and successes into practical interventions in malaria endemic countries in Africa and elsewhere.展开更多
Background and Aims:Syntaxin 5(STX5)is a member of the syntaxin or target-soluble SNAP receptor(t-SNARE)fam-ily and plays a critical role in autophagy.However,its function and molecular mechanism in tumor cell migrati...Background and Aims:Syntaxin 5(STX5)is a member of the syntaxin or target-soluble SNAP receptor(t-SNARE)fam-ily and plays a critical role in autophagy.However,its function and molecular mechanism in tumor cell migration are still un-known.The role of STX5 in influencing hepatocellular carci-noma(HCC)is an important topic in our research.Methods:By using quantitative reverse transcription polymerase chain reaction(qPCR),western blotting,and immunohistochemical analysis of RNA and protein in tissues,we comprehensively evaluated data sets from public databases and clinical patient cohorts for STX5.The correlation of STX5 expression with the clinicopathological characteristics of HCC patients were assessed.In addition,we predicted signal pathways from dif-ferentially expressed genes(DEGs)and the Cancer Genome Atlas(TCGA)databases,and confirmed the prediction using integrated transcriptome and RNA-seq.We further investi-gated the underlying mechanisms of STX5 in the migration and adhesion of HCC cells both in vitro and in vivo.Results:In the TCGA dataset and our patient cohort,STX5 levels were significantly higher in HCC tissues than in adjacent normal liver tissues.At the same time,high expression of STX5 pre-dicted worse prognosis in patients with liver cancer.High ex-pression of STX5 indicates the decrease of adhesion and the increase of migration of HCC cells,and the conversion of epi-thelial-mesenchymal transition(EMT)in vitro via PI3K/mTOR pathway activation.Conversely,when Sirolimus,a phospho-inositide 3-kinase(PI3K)/AKT/mechanistic target of rapa-mycin(mTOR)inhibitor acts on cells simultaneously,STX5 overexpression-mediated enhancement of HCC metastasis is reversed.Double-negative regulation of STX5 and mTOR further enhanced the inhibitory effect of STX5 on HCC me-tastasis.In vivo,STX5 knockdown inhibited the metastasis of HCC cells.Conclusions:Our study demonstrates a novel research result that STX5 promotes HCC metastasis through PI3K/mTOR pathway.We believe that combined inhibition of STX5 and mTOR is a potential treatment for effectively pro-longing patient survival and inhibiting HCC metastasis.展开更多
基金This work was supported by National Institute of Parasitic Disease,Chinese Center for Disease Control and Prevention,Shanghai 200025,Ministry of Science and Technology,Ministry of Human Resources and Social Security of P.R.ChinaP.R.China Postdoctoral Science Foundation,P.R.China-Africa Sciences and Technology Partnership Program,2011Thanks to the partial support of the Chinese National Science and Technology Major Program(2012ZX10004220)。
文摘This review aims at providing synthetic information with scientific evidence on the trends in the malaria events from 1960 to 2011,with the hope that it will help policy makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in both Sub-Sahara Africa and in the People’s Republic of China by highlighting the achievements,progress and challenges in research on moving malaria from epidemic status towards elimination.Our findings showed that since 1960,malaria control programmes in most countries have been disjointed and not harmonized.Interestingly,during the last decade,the causal factors of the unprecedented and substantial decline in malaria morbidity and mortality rates in most vulnerable groups in these endemic areas are multifaceted,including not only the spread of malaria and its related effects but also political and financial willingness,commitment and funding by governments and international donors.The benefits of scaling up the impact of malaria coverage interventions,improvement of health system approaches and sustained commitment of stakeholders are highlighted,although considerable efforts are still necessary in Sub-Sahara Africa.Furthermore,novel integrated control strategies aiming at moving malaria from epidemic status to control towards elimination,require solid research priorities both for sustainability of the most efficient existing tools and intervention coverage,and in gaining more insights in the understanding of the epidemiology,pathogenesis,vector dynamics,and socioeconomic aspects of the disease.In conclusion,political commitment and financial investment of stakeholders in sustaining the scaling up impact of malaria control interventions,networking between African and Chinese scientists,and their Western partners are urgently needed in upholding the recent gains,and in translating lessons learnt from the Chinese malaria control achievements and successes into practical interventions in malaria endemic countries in Africa and elsewhere.
基金Natural Science Foundation of Shandong Province(CN)(ZR201911030198).
文摘Background and Aims:Syntaxin 5(STX5)is a member of the syntaxin or target-soluble SNAP receptor(t-SNARE)fam-ily and plays a critical role in autophagy.However,its function and molecular mechanism in tumor cell migration are still un-known.The role of STX5 in influencing hepatocellular carci-noma(HCC)is an important topic in our research.Methods:By using quantitative reverse transcription polymerase chain reaction(qPCR),western blotting,and immunohistochemical analysis of RNA and protein in tissues,we comprehensively evaluated data sets from public databases and clinical patient cohorts for STX5.The correlation of STX5 expression with the clinicopathological characteristics of HCC patients were assessed.In addition,we predicted signal pathways from dif-ferentially expressed genes(DEGs)and the Cancer Genome Atlas(TCGA)databases,and confirmed the prediction using integrated transcriptome and RNA-seq.We further investi-gated the underlying mechanisms of STX5 in the migration and adhesion of HCC cells both in vitro and in vivo.Results:In the TCGA dataset and our patient cohort,STX5 levels were significantly higher in HCC tissues than in adjacent normal liver tissues.At the same time,high expression of STX5 pre-dicted worse prognosis in patients with liver cancer.High ex-pression of STX5 indicates the decrease of adhesion and the increase of migration of HCC cells,and the conversion of epi-thelial-mesenchymal transition(EMT)in vitro via PI3K/mTOR pathway activation.Conversely,when Sirolimus,a phospho-inositide 3-kinase(PI3K)/AKT/mechanistic target of rapa-mycin(mTOR)inhibitor acts on cells simultaneously,STX5 overexpression-mediated enhancement of HCC metastasis is reversed.Double-negative regulation of STX5 and mTOR further enhanced the inhibitory effect of STX5 on HCC me-tastasis.In vivo,STX5 knockdown inhibited the metastasis of HCC cells.Conclusions:Our study demonstrates a novel research result that STX5 promotes HCC metastasis through PI3K/mTOR pathway.We believe that combined inhibition of STX5 and mTOR is a potential treatment for effectively pro-longing patient survival and inhibiting HCC metastasis.