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
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
Objective： To observe the effect of Huannao Yicong Prescription （还脑益聪方, HNYC, a Chinese medical compound） extract on β-amyloid precursor protein （APP） metabolic signal transductionrelated protein kinase C ...Objective： To observe the effect of Huannao Yicong Prescription （还脑益聪方, HNYC, a Chinese medical compound） extract on β-amyloid precursor protein （APP） metabolic signal transductionrelated protein kinase C （PKC）, tyrosine amyloid protein kinase （TrKA）, and glycogen synthase kinase-3 （GSK-3） in brain tissue of transgenic mouse dementia model induced by APP. Methods： Sixty dementia model transgenic 3-month-old mice induced by APP695V7171 were randomly allocated in four groups： the model group （A）, the Donepezil （0.65×10^-3 g.kg-1.d-1）-treated group （B）, and the two HNYC-treated groups （C and D） with high dosage （2.8 g.kg^-1.d^-1） and low dosage （1.4 g.kg^-1.d^-1） of HNYC extract, respectively, 15 mice in each group. Besides, a normal control group was set up with 15 C57BL/6J mice with the same age and genetic background as the model mice. The drugs for treatment were administered once a day by dissolving in equal-volume distilled water through gastric infusion, continued for 6 months, to mice in group A and to normal control group equal-volume distilled water was administered instead. Spatial learning and memory capacity of mice were observed by Morris water maze; their one-time escape response memory capacity was tested by diving platform; and changes of PKC, TrkA, and GSK-3 levels in hippocampus and cortex of brain were detected by Western blotting. Results： HNYC extract showed significant effects on increasing the time of model mice for swimming through the flat roof and the swimming time and path in the fourth quadrant （P〈0.05 or P〈0.01）. Diving platform test showed that the latent times in Groups B and C were longer than that in Group A significantly （P〈0.05 and P〈0.01）. Compared with the normal control group, PKC and TrkA protein expression levels in hippocampus and cortex of model mice＇s brain lowered significantly （P〈0.01）, while GSK-3 protein expression increased significantly （P〈0.01）; compared with Group A （the model group）, hippocampal and cortical levels of PKC protein expression in the intervened groups （B-D） as well as those of TrkA in Group C were higher （P〈0.01 or P〈0.05）, while hippocampal levels of GSK-3 in intervened groups were lower （P〈0.01）. Conclusion： HNYC extract could obviously increase the protein expressions of PKC and TrkA and decrease the expression of GSK-3 protein in brain tissue of transgenetic mice model of dementia, and regulate APP metabolic signal transduction path, and thus to suppress the production of A β, which is one of the dominant mechanisms for improving learning/memory capacity of dementia model animals.展开更多
Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate from the bone marrow, and influence each other in vivo. To elucidate the mechanism that controls the interrelationship between these two c...Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate from the bone marrow, and influence each other in vivo. To elucidate the mechanism that controls the interrelationship between these two cell types, the signaling path- way of signal transducer and activator of transcription 3 (Stat3) was activated by overexpressing Stat3C in a newly established c-fms-rtTA/(TetO)7-CMV-Stat3C bitransgenic mouse model, In this system, Stat3C-Flag fusion protein was overexpressed in myeloid lineage cells after doxycycline treatment. Stat3C overexpression induced systematic elevation of macrophages and neutrophils in multiple organs. In the lung, tissue neoplastic pneumocyte proliferation was observed. After in vitro cultured hSP-B 1.5-kb lacZ BMSCs were injected into the bitransgenic mice, BMSCs were able to repopulate in multiple organs, self-renew in the bone marrow and spleen, and convert into alveolar type II epithelial cells. The bone marrow transplantation study indicated that increases of myeloid lineage cells and BMSC-AT II cell conversion were due to malfunction of myeloid progenitor cells as a result of Stat3C overexpression. The study supports the concept that activation of the Stat3 pathway in myeloid cells plays an important role in BMSC function, including homing, repopulating and converting into residential AT II epithelial cells in the lung.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 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 the National Natural Science Foundation of China(No.30873338)the Major New Drug Projects of the Ministry of Science and Technology of P.R China(No 2009ZX09103-391)
文摘Objective： To observe the effect of Huannao Yicong Prescription （还脑益聪方, HNYC, a Chinese medical compound） extract on β-amyloid precursor protein （APP） metabolic signal transductionrelated protein kinase C （PKC）, tyrosine amyloid protein kinase （TrKA）, and glycogen synthase kinase-3 （GSK-3） in brain tissue of transgenic mouse dementia model induced by APP. Methods： Sixty dementia model transgenic 3-month-old mice induced by APP695V7171 were randomly allocated in four groups： the model group （A）, the Donepezil （0.65×10^-3 g.kg-1.d-1）-treated group （B）, and the two HNYC-treated groups （C and D） with high dosage （2.8 g.kg^-1.d^-1） and low dosage （1.4 g.kg^-1.d^-1） of HNYC extract, respectively, 15 mice in each group. Besides, a normal control group was set up with 15 C57BL/6J mice with the same age and genetic background as the model mice. The drugs for treatment were administered once a day by dissolving in equal-volume distilled water through gastric infusion, continued for 6 months, to mice in group A and to normal control group equal-volume distilled water was administered instead. Spatial learning and memory capacity of mice were observed by Morris water maze; their one-time escape response memory capacity was tested by diving platform; and changes of PKC, TrkA, and GSK-3 levels in hippocampus and cortex of brain were detected by Western blotting. Results： HNYC extract showed significant effects on increasing the time of model mice for swimming through the flat roof and the swimming time and path in the fourth quadrant （P〈0.05 or P〈0.01）. Diving platform test showed that the latent times in Groups B and C were longer than that in Group A significantly （P〈0.05 and P〈0.01）. Compared with the normal control group, PKC and TrkA protein expression levels in hippocampus and cortex of model mice＇s brain lowered significantly （P〈0.01）, while GSK-3 protein expression increased significantly （P〈0.01）; compared with Group A （the model group）, hippocampal and cortical levels of PKC protein expression in the intervened groups （B-D） as well as those of TrkA in Group C were higher （P〈0.01 or P〈0.05）, while hippocampal levels of GSK-3 in intervened groups were lower （P〈0.01）. Conclusion： HNYC extract could obviously increase the protein expressions of PKC and TrkA and decrease the expression of GSK-3 protein in brain tissue of transgenetic mice model of dementia, and regulate APP metabolic signal transduction path, and thus to suppress the production of A β, which is one of the dominant mechanisms for improving learning/memory capacity of dementia model animals.
基金supported by the National Institutes of Health (Grant Nos. CA138759 and CA152099 to Yan CongHL087001 to Du Hong)
文摘Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate from the bone marrow, and influence each other in vivo. To elucidate the mechanism that controls the interrelationship between these two cell types, the signaling path- way of signal transducer and activator of transcription 3 (Stat3) was activated by overexpressing Stat3C in a newly established c-fms-rtTA/(TetO)7-CMV-Stat3C bitransgenic mouse model, In this system, Stat3C-Flag fusion protein was overexpressed in myeloid lineage cells after doxycycline treatment. Stat3C overexpression induced systematic elevation of macrophages and neutrophils in multiple organs. In the lung, tissue neoplastic pneumocyte proliferation was observed. After in vitro cultured hSP-B 1.5-kb lacZ BMSCs were injected into the bitransgenic mice, BMSCs were able to repopulate in multiple organs, self-renew in the bone marrow and spleen, and convert into alveolar type II epithelial cells. The bone marrow transplantation study indicated that increases of myeloid lineage cells and BMSC-AT II cell conversion were due to malfunction of myeloid progenitor cells as a result of Stat3C overexpression. The study supports the concept that activation of the Stat3 pathway in myeloid cells plays an important role in BMSC function, including homing, repopulating and converting into residential AT II epithelial cells in the lung.
