AIM: To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population.
AIM:To investigate the relationship between Apolipoprotein C3(APOC3)(-455T>C) polymorphism and nonalcoholic fatty liver disease(NAFLD) in the Southern Chinese han population.METHODS:In this prospective case-control...AIM:To investigate the relationship between Apolipoprotein C3(APOC3)(-455T>C) polymorphism and nonalcoholic fatty liver disease(NAFLD) in the Southern Chinese han population.METHODS:In this prospective case-control study,we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese han population at The First Affiliated Hospital,Sun Yat-sen University,from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3(-455T>C) variants.RESULTS:After adjusting for age,gender,and bodymass index,TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype,with adjusted odds ratios(ORs) of 1.77(95%CI:1.16-2.72) and 2.80(95%CI:1.64-4.79),respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance(IR) than those of the TT genotype,with an OR of 3.24(95%CI:1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension,hypertriglyceridemia,and low levels of high-density lipoprotein cholesterol(hDL)(P < 0.05). No association was found between the APOC3(-455T>C) polymorphism and obesity,impaired glucose tolerance,hyperuricemia,hypercholesterolemia,or high levels of low-density lipoprotein cholesterol(LDL)(P > 0.05).CONCLUSION:APOC3(-455T>C) genetic variation is involved in the susceptibility to developing NAFLD,IR,hypertension,hypertriglyceridemia,and low hDL in the Southern Chinese han population.展开更多
BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely ...BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.展开更多
Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the mos...Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.展开更多
AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and l...AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile.展开更多
The expression of antigens in transgenic plants has increasingly been used as an alternative to the classical methodologies for the development of experimental vaccines.This paper reports here the development of a nov...The expression of antigens in transgenic plants has increasingly been used as an alternative to the classical methodologies for the development of experimental vaccines.This paper reports here the development of a novel oral immunization system for foot-and-mouth disease （FMD） in transgenic maize with two serotypes of the structural protein VP1 of the foot-and-mouth disease virus （FMDV） viz.,O-and Asia 1-type,respectively.The transgenic plantlets were identified and investigated by polymerase chain reaction （PCR）,Southern blot,and real-time PCR.Moreover,it was found that the VP1 genes in transgenic plants could be transmitted stably to the next generation through PCR detection.To our knowledge,this is the first report in an attempt to induce a protective systemic antibody response in animals by feeding the transgenic plants in which two serotypes antigen protein of FMDV expressed together.Results of the experiment provide the possibility of using plant-based vaccines as feedstuff or feedstuff additives.展开更多
Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and gr...Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and growth factors for lymphangiogenesis. Importantly, lymphatic endothelial receptor tyrosine kinase VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype. It demonstrates the plasticity of endothelial cells and offers the possibility of transcriptional reprogramming of vascular endothelial cells as future putative therapeutic applications.展开更多
C型凝集素(C-typelectin)是一类能与糖类结合的非抗体的蛋白质或糖蛋白家族,为了研究C型凝集素基因在日本沼虾组织分布、细胞定位和细菌感染过程中的表达情况,本研究应用cDNA末端快速克隆(rapid-amplification of cDNA ends,RACE)技术...C型凝集素(C-typelectin)是一类能与糖类结合的非抗体的蛋白质或糖蛋白家族,为了研究C型凝集素基因在日本沼虾组织分布、细胞定位和细菌感染过程中的表达情况,本研究应用cDNA末端快速克隆(rapid-amplification of cDNA ends,RACE)技术首次克隆了日本沼虾C型凝集素结构域家族3基因(MnLec3)的全长序列,通过实时荧光定量PCR(qRT-PCR)分析MnLec3基因在不同组织、细菌感染后不同时间的表达水平,Westernblot和免疫荧光分别分析蛋白的表达水平和细胞定位。结果显示,MnLec3基因cDNA全长1357bp,包括125bp的5′末端非翻译区(UTR)、1026bp的开放阅读框(ORF)和206bp的3′UTR,其中开放阅读框编码341个氨基酸。氨基酸序列比对显示,日本沼虾MnLec3基因含有保守钙结合点(Met1-Glu17)和糖识别结构域(CRD)。同源性分析结果显示,MnLec3与罗氏沼虾C型凝集素3相似度较高;邻接法(Neighbor-Joining,NJ)进化树分析结果显示,MnLec3与其他甲壳动物C型凝集素聚为一支。通过构建原核表达载体获得体外重组蛋白rMnLec3,并将纯化重组蛋白免疫大鼠获得抗血清,免疫荧光结果显示,绿色荧光信号主要在肝胰腺细胞核中表达。qRT-PCR结果显示,MnLec3在日本沼虾所检测组织中均表达,其中肝胰腺中表达量最高,血细胞次之;与对照组相比,在嗜水气单胞菌刺激12~48h时MnLec3表达量显著升高,48h表达量最高,Western blot分析结果显示,MnLec3蛋白表达丰度与基因表达模式基本相似,提示克隆得到的MnLec3参与日本沼虾抵御细菌入侵的免疫过程。展开更多
基金Supported by National Natural Science Foundation of China,No.81170337/H0304
文摘AIM: To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population.
基金Supported by Natural Scientific Foundation of Guangdong Province,No.S2012040007685Doctoral Program Foundation of Institutions of Higher Education of China,No.20120171120090National Natural Science Foundation of China,No.81301769 and No.81170392
文摘AIM:To investigate the relationship between Apolipoprotein C3(APOC3)(-455T>C) polymorphism and nonalcoholic fatty liver disease(NAFLD) in the Southern Chinese han population.METHODS:In this prospective case-control study,we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese han population at The First Affiliated Hospital,Sun Yat-sen University,from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3(-455T>C) variants.RESULTS:After adjusting for age,gender,and bodymass index,TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype,with adjusted odds ratios(ORs) of 1.77(95%CI:1.16-2.72) and 2.80(95%CI:1.64-4.79),respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance(IR) than those of the TT genotype,with an OR of 3.24(95%CI:1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension,hypertriglyceridemia,and low levels of high-density lipoprotein cholesterol(hDL)(P < 0.05). No association was found between the APOC3(-455T>C) polymorphism and obesity,impaired glucose tolerance,hyperuricemia,hypercholesterolemia,or high levels of low-density lipoprotein cholesterol(LDL)(P > 0.05).CONCLUSION:APOC3(-455T>C) genetic variation is involved in the susceptibility to developing NAFLD,IR,hypertension,hypertriglyceridemia,and low hDL in the Southern Chinese han population.
基金Supported by the National Natural Science Foundation of China,No.U1504815 and No.U1504808
文摘BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.
基金Supported by The American Heart Association(13SDG14640038)2012 Yale Center for Clinical Investigation cholar award to Santoro NThis publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Advancing Translational Science,a component of the National Institutes of Health(NIH),and NIH roadmap for Medical Research,Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH
文摘Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.
基金Supported by Medical University,Lodz,Poland,No.502-03/1-117-01/502-14-061
文摘AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile.
基金supported by the National Natural Science Foundation of China (30800687 and 31071434)the Applied Basic Research Program of Sichuan Provincial Science and Technology Department,China (2008JY0096)+1 种基金the Foundation for Young Scientists of Sichuan Provincial Education Department,China(09ZB051)the Youth Innovation Project of Sichuan Agricultural University,China,the Postdoctoral Project of Sichuan Agricultural University,China
文摘The expression of antigens in transgenic plants has increasingly been used as an alternative to the classical methodologies for the development of experimental vaccines.This paper reports here the development of a novel oral immunization system for foot-and-mouth disease （FMD） in transgenic maize with two serotypes of the structural protein VP1 of the foot-and-mouth disease virus （FMDV） viz.,O-and Asia 1-type,respectively.The transgenic plantlets were identified and investigated by polymerase chain reaction （PCR）,Southern blot,and real-time PCR.Moreover,it was found that the VP1 genes in transgenic plants could be transmitted stably to the next generation through PCR detection.To our knowledge,this is the first report in an attempt to induce a protective systemic antibody response in animals by feeding the transgenic plants in which two serotypes antigen protein of FMDV expressed together.Results of the experiment provide the possibility of using plant-based vaccines as feedstuff or feedstuff additives.
文摘Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and growth factors for lymphangiogenesis. Importantly, lymphatic endothelial receptor tyrosine kinase VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype. It demonstrates the plasticity of endothelial cells and offers the possibility of transcriptional reprogramming of vascular endothelial cells as future putative therapeutic applications.
文摘C型凝集素(C-typelectin)是一类能与糖类结合的非抗体的蛋白质或糖蛋白家族,为了研究C型凝集素基因在日本沼虾组织分布、细胞定位和细菌感染过程中的表达情况,本研究应用cDNA末端快速克隆(rapid-amplification of cDNA ends,RACE)技术首次克隆了日本沼虾C型凝集素结构域家族3基因(MnLec3)的全长序列,通过实时荧光定量PCR(qRT-PCR)分析MnLec3基因在不同组织、细菌感染后不同时间的表达水平,Westernblot和免疫荧光分别分析蛋白的表达水平和细胞定位。结果显示,MnLec3基因cDNA全长1357bp,包括125bp的5′末端非翻译区(UTR)、1026bp的开放阅读框(ORF)和206bp的3′UTR,其中开放阅读框编码341个氨基酸。氨基酸序列比对显示,日本沼虾MnLec3基因含有保守钙结合点(Met1-Glu17)和糖识别结构域(CRD)。同源性分析结果显示,MnLec3与罗氏沼虾C型凝集素3相似度较高;邻接法(Neighbor-Joining,NJ)进化树分析结果显示,MnLec3与其他甲壳动物C型凝集素聚为一支。通过构建原核表达载体获得体外重组蛋白rMnLec3,并将纯化重组蛋白免疫大鼠获得抗血清,免疫荧光结果显示,绿色荧光信号主要在肝胰腺细胞核中表达。qRT-PCR结果显示,MnLec3在日本沼虾所检测组织中均表达,其中肝胰腺中表达量最高,血细胞次之;与对照组相比,在嗜水气单胞菌刺激12~48h时MnLec3表达量显著升高,48h表达量最高,Western blot分析结果显示,MnLec3蛋白表达丰度与基因表达模式基本相似,提示克隆得到的MnLec3参与日本沼虾抵御细菌入侵的免疫过程。
