BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-i...BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-inflmmatory cytokines.The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγexpression in the liver and gallbladder epithelium,and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. METHODS:A total of 40 Golden Syrian male hamsters(4 weeks old)were randomly assigned to four groups(basal diet control; basal diet+pavastatin;high cholesterol diet;high cholesterol diet+pravastatin).All hamsters were 11 weeks old at the end of the experiment.The liver,gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARαand PPARγwere performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. RESULTS:In the gallbladder and liver of the hamsters, pravastatin activated the PPARαand PPARγexpression of gallbladder epithelial cells and hepatocytes,and particularly the response of PPARγwas much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. CONCLUSION:Pravastatin is an effective medication to activate PPARs(especially PPARγ)in the liver and the gallbladder epithelium of hamsters,and contributes to the prevention of gallstone formation.展开更多
BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among t...BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor(PPAR)α, PPARγ, liver X receptor α(LXRα), farnesoid X receptor(FXR), ABCG5, ABCG8, and 7α-hydroxylase(CYP7A1) which are directly involved in the cholesterol saturation index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently. CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRαand CYP7A1 in human hepatocytes.展开更多
Objective:Immunotherapy that blocks inhibitory pathways in T lymphocytes,such as the PD-L1/PD-1 axis,is undergoing evaluation for various solid tumors.Notably,this emerging therapeutic approach is already in clinical ...Objective:Immunotherapy that blocks inhibitory pathways in T lymphocytes,such as the PD-L1/PD-1 axis,is undergoing evaluation for various solid tumors.Notably,this emerging therapeutic approach is already in clinical trials for advanced hepatocellular carcinoma(HCC).展开更多
Gastric outlet obstruction(GOO)is a medical condition characterized by epigastric pain and postprandial vomiting due to mechanical obstruction.The obstructions typically involved in GOO can be benign or malignant.Pept...Gastric outlet obstruction(GOO)is a medical condition characterized by epigastric pain and postprandial vomiting due to mechanical obstruction.The obstructions typically involved in GOO can be benign or malignant.Peptic ulcer disease is the most common cause of benign GOO,and malignant causes include gastric cancer,lymphoma,and gastrointestinal stromal tumor.With the eradication of Helicobacter pylori(H.pylori)and the use of proton pump inhibitors,the predominant causes have changed from benign to malignant diseases.Treatment of GOO depends on the underlying cause:Proton pump inhibitors,H.pylori eradication,endoscopic treatments including balloon dilatation or the placement of self-expandable stents,or surgery.展开更多
“9 11”国家纪念博物馆（THE NATIONAL SEPTEMBER 11MEMORIAL AND MUSEUM）坐落于纽约世贸中心遗址之上,占地面积约1万平方米,耗资7亿美元,堪称美国近年来耗资最大的纪念博物馆工程。该博物馆于2006年3月13日动工,2011年9月11日“9 11...“9 11”国家纪念博物馆（THE NATIONAL SEPTEMBER 11MEMORIAL AND MUSEUM）坐落于纽约世贸中心遗址之上,占地面积约1万平方米,耗资7亿美元,堪称美国近年来耗资最大的纪念博物馆工程。该博物馆于2006年3月13日动工,2011年9月11日“9 11”恐怖袭击十周年之际部分对外开放,最终于2014年5月21日正式对外开放。展开更多
基金supported by a grant from Kyung Hee University Research(20071618)
文摘BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-inflmmatory cytokines.The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγexpression in the liver and gallbladder epithelium,and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. METHODS:A total of 40 Golden Syrian male hamsters(4 weeks old)were randomly assigned to four groups(basal diet control; basal diet+pavastatin;high cholesterol diet;high cholesterol diet+pravastatin).All hamsters were 11 weeks old at the end of the experiment.The liver,gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARαand PPARγwere performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. RESULTS:In the gallbladder and liver of the hamsters, pravastatin activated the PPARαand PPARγexpression of gallbladder epithelial cells and hepatocytes,and particularly the response of PPARγwas much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. CONCLUSION:Pravastatin is an effective medication to activate PPARs(especially PPARγ)in the liver and the gallbladder epithelium of hamsters,and contributes to the prevention of gallstone formation.
文摘BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor(PPAR)α, PPARγ, liver X receptor α(LXRα), farnesoid X receptor(FXR), ABCG5, ABCG8, and 7α-hydroxylase(CYP7A1) which are directly involved in the cholesterol saturation index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently. CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRαand CYP7A1 in human hepatocytes.
文摘Objective:Immunotherapy that blocks inhibitory pathways in T lymphocytes,such as the PD-L1/PD-1 axis,is undergoing evaluation for various solid tumors.Notably,this emerging therapeutic approach is already in clinical trials for advanced hepatocellular carcinoma(HCC).
文摘Gastric outlet obstruction(GOO)is a medical condition characterized by epigastric pain and postprandial vomiting due to mechanical obstruction.The obstructions typically involved in GOO can be benign or malignant.Peptic ulcer disease is the most common cause of benign GOO,and malignant causes include gastric cancer,lymphoma,and gastrointestinal stromal tumor.With the eradication of Helicobacter pylori(H.pylori)and the use of proton pump inhibitors,the predominant causes have changed from benign to malignant diseases.Treatment of GOO depends on the underlying cause:Proton pump inhibitors,H.pylori eradication,endoscopic treatments including balloon dilatation or the placement of self-expandable stents,or surgery.
文摘“9 11”国家纪念博物馆（THE NATIONAL SEPTEMBER 11MEMORIAL AND MUSEUM）坐落于纽约世贸中心遗址之上,占地面积约1万平方米,耗资7亿美元,堪称美国近年来耗资最大的纪念博物馆工程。该博物馆于2006年3月13日动工,2011年9月11日“9 11”恐怖袭击十周年之际部分对外开放,最终于2014年5月21日正式对外开放。
