BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may pl...BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.展开更多
Objective To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets ...Objective To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, fiver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 34 folds compared with the conlrol value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.展开更多
Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol...Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.展开更多
Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternati...Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-mediated delivery of peripheral cholesterol to the liver for biliary excretion out of the body. However, recent studies have revealed a novel pathway for RCT that does not rely on biliary secretion. This nonbiliary pathway rather involves the direct excretion of cholesterol by the proximal small intestine. Compared to RCT therapies that augment biliary sterol loss, modulation of non-biliary fecal sterol loss through the intestine is a much more attractive therapeutic strategy, given that excessive biliary cholesterol secretion can promote gallstone formation. However, we are at an early stage in understanding the molecular mechanisms regulating the non-biliary pathway for RCT, and much additional work is required in order to effectively target this pathway for CHD prevention. The purpose of this review is to discuss our current understanding of biliary and nonbiliary contributions to RCT with particular emphasis on the possibility of targeting the intestine as an inducible cholesterol secretory organ.展开更多
AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieve...AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.展开更多
IM To elucidate the importance and the changing patterns of biliary concanavalin Abinding proteins (CPs) in the early stage of cholesterol gallstone.METHODS CPs concentrations and nucleation activities were measured...IM To elucidate the importance and the changing patterns of biliary concanavalin Abinding proteins (CPs) in the early stage of cholesterol gallstone.METHODS CPs concentrations and nucleation activities were measured by lectin affinity chromatography in biles of patients with cholesterol gallstone, pigment gallstone, gallbladder cholesterosis and nonbiliary diseases.RESULTS The concentrations of CPs were much higher in patients with cholesterol gallstone (039g/L±011g/L, n=36, P<001) or gallbladder cholesterosis (040g/L±009g/L, n=9, P<001) than in those with pigment gallstone (026g/L±012g/L, n=7) and/or nonbiliary diseases (027g/L±009g/L, n=10). Pronucleating activities were much stronger in patients with cholesterol gallstones (nucleation time ratio: 057±021, n=5, P<001 vs pigment gallstone and/or nonbiliary diseases) and gallbladder cholesterosis (nucleation time ratio: 044±023, n=5, P<001 vs pigment gallstone or nonbilliary diseases). The binding percentages of CPs to model biliary vesicles were also higher in patients with cholesterol gallstones (n=6) than those with pigment gallstones (n=6) (24%±09% vs 09%±05%, P<001).CONCLUSION Hypersecretion of CPs, especially those in vesicular phase may be the important changes in the early stage of cholesterol gallstone.展开更多
BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2...BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2), and multiple drug resistance 3 (MDR3 ) are 3 well-known transporting proteins, their effect on lithogenesis has not been elucidated. This study was undertaken to examine the relationship between BSEP, MRP2, MDR3, and cholesterol calculus formation. METHODS: Liver tissue specimens were taken from 20 patients with cholesterol calculus and from 10 patients with normal liver. mRNA and protein expressions of BSEP, MRP2, and MDR3 were determined by reverse tran-scriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. This study was approved by the ethics committee of China Medical University and informed consent was obtained from all patients. RESULTS: mRNA and protein expressions of BSEP, MRP2, and MDR3 were significantly down-regulated in the liver tissue of the patients with cholesterol calculus compared with normal liver tissue of the controls. CONCLUSION: The down-regulation of BSEP, MRP2, and MDR3 may be correlated with the formation of cholesterol calculus.展开更多
AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William...AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.展开更多
Objective:To evaluate the ability of lactic acid bacteria(LAB)strains isolated from fermented mustard to lower the cholesterol in vitro.Methods:The ability of 50 LAB strains isolated from fermented mustard on lowering...Objective:To evaluate the ability of lactic acid bacteria(LAB)strains isolated from fermented mustard to lower the cholesterol in vitro.Methods:The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method.The LAB isolates were analyzed for their resistance to acid and bile salt.Strains with lowering cholesterol activity,were determined adherence to Caco-2 cells.Results:Strain B0007,B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC17010.The isolated strains showed tolerance to pH 3.0 for 3h despite variations in the degree of viability and bile-tolerant strains,with more than 10~s CFU/mL after incubation for 24 h at 1%oxigall in MRS.In addition,strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines.Conclusions:These strains B0007 and B0022 may be potential functional sources for cholesterollowering activities as well as adhering to Caco-2 cell lines.展开更多
Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 ...Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 days. In male rats, body weight gained, and the levels of total lipids, total cholesterol and triglycerides in the liver were significantly decreased as the dose of capsaicinoids increased. On the other hand, plasma total cholesterol (TC), triglycerides (TG), HDL- and LDL-cholesterol concentration and liver weight were not affected by capsaicinoids. While in female rats, plasma TC, TG, HDL-C and LDL-C concentration, liver total lipids, TC and TG concentration were significantly decreased as the dose of capsaicinoids increased. The mRNA level of hepatic TRPV1, ileac ASBT and IBABP were increased as the dose of capsaicinoids increased in all rats groups. The mRNA level of hepatic HMG-CoA reductase, CYP7A1 and FXR were significantly decreased in female rats groups. These results show that the hypocholesterolemic effect of capsaicinoids in dose-dependent manner in rats was mediated by inhibited synthesis of endogenous cholesterol, female rats were more sensitive than male rats on hypolipidemic effect of capsaicinoids.展开更多
In the present study, 20 selected Lactobacillus strains already characterized in a previous research for their capability to grow in conditions simulating the intestinal environment, their resistance to antibiotics, t...In the present study, 20 selected Lactobacillus strains already characterized in a previous research for their capability to grow in conditions simulating the intestinal environment, their resistance to antibiotics, their antibacterial activity and their adhesion capability to intestinal human Caco-2 TC7 and HT-29 MTX cell lines, were further investigated to explore more their probiotic properties. Growth behaviour in the presence of prebiotic (fructooligosac-charides (FOS) and lactulose) at a concentration of 2%, cholesterol removal by measuring the residual cholesterol in medium supplemented with cholesterol, ability to deconjugate bile salts using BSH enzyme and antioxidant activity of culture supernatant of Lactobacillus strains by ABTS·+ and DPPH methods were analyzed. All probiotic strains demonstrated important prebiotic assimilation (P > 0.05) even with OD600 > 3 after 30 h of contact, cholesterol removal ability with maximum percentage of 57% after 24 h of contact and they were found to liberate significantly (P < 0.05) more cholic acid with maximum of 0.40 mM of sodium glycocholate, 0.33 mM of sodium taurocholate and 0.41 mM of their mixte and scavenge both radicals with 52% and 2.19% of ABTS·+ and DPPH respectively. This study confirmed the suitability of these probiotic strains for application in functional food formulations especially where cholesterol reduction and antioxidant activity in food are needed to assess possible in vivo human health benefits.展开更多
目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附...目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附属医院纳入正常及脾虚痰浊血脂异常受试者共计180例,按照就诊顺序随机分为正常组、模型组、健脾祛痰方组,每组60例。所有组别均予健康宣教,健脾祛痰方组予健脾祛痰方颗粒剂冲服,治疗疗程为2个月。采用全自动分析仪检测所有受试者血清胆固醇(Total Cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low Density Lipoprotein,LDL-C)、高密度脂蛋白胆固醇(High Density Lipoprotein,HDL-C)水平,用中医证候积分量表评定患者中医证候疗效,酶联免疫吸附测定法测定受试者血清人成纤维细胞生长因子19(FGF19)的表达水平,16SrRNA高通量测序技术检测受试者粪便标本肠道菌群的结构变化。结果脾虚痰浊型血脂异常患者经健脾祛痰方治疗后血脂水平,中医证候积分较治疗前明显改善,血清中FGF19含量明显降低;健脾祛痰方组血脂疗效、中医证候积分总有效率显著优于模型组。高脂人群菌群多样性和物种丰度与正常人群相比明显减弱。有益菌减少,肠杆菌过生长,肠道菌群结构被破坏。健脾祛痰方组患者用药后样本间差异明显,各分类水平物种组成比例发生变化,编码胆盐水解酶(Bile Salt Hydrolase,BSH)相关微生物丰度降低。用药后肠道中的有害菌肠杆菌目(Enterobacteriales)减少,肠道菌群平衡有所恢复。结论健脾祛痰法能够显著降低血脂异常患者TC、TG、LDL-C水平,改善中医证候,其机制可能通过调节肠道菌群和胆汁酸代谢抑制FXR信号传导通路以降脂。展开更多
基金This study was supported by a grant from the Health Bureau of Tianjin, China(No. 00kyzd8).
文摘BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.
文摘Objective To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, fiver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 34 folds compared with the conlrol value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.
基金Supported by A grant from the Netherlands Organization for Scientif ic Research (NWO, VIDI Grant 917-56-358)
文摘Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.
基金Supported by Pathway to Independence Grants (5R00HL088528 to Temel RE and 1K99-HL096166 to Brown JM) from the National Heart, Lung, and Blood Institute
文摘Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-mediated delivery of peripheral cholesterol to the liver for biliary excretion out of the body. However, recent studies have revealed a novel pathway for RCT that does not rely on biliary secretion. This nonbiliary pathway rather involves the direct excretion of cholesterol by the proximal small intestine. Compared to RCT therapies that augment biliary sterol loss, modulation of non-biliary fecal sterol loss through the intestine is a much more attractive therapeutic strategy, given that excessive biliary cholesterol secretion can promote gallstone formation. However, we are at an early stage in understanding the molecular mechanisms regulating the non-biliary pathway for RCT, and much additional work is required in order to effectively target this pathway for CHD prevention. The purpose of this review is to discuss our current understanding of biliary and nonbiliary contributions to RCT with particular emphasis on the possibility of targeting the intestine as an inducible cholesterol secretory organ.
基金Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf
文摘AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
文摘IM To elucidate the importance and the changing patterns of biliary concanavalin Abinding proteins (CPs) in the early stage of cholesterol gallstone.METHODS CPs concentrations and nucleation activities were measured by lectin affinity chromatography in biles of patients with cholesterol gallstone, pigment gallstone, gallbladder cholesterosis and nonbiliary diseases.RESULTS The concentrations of CPs were much higher in patients with cholesterol gallstone (039g/L±011g/L, n=36, P<001) or gallbladder cholesterosis (040g/L±009g/L, n=9, P<001) than in those with pigment gallstone (026g/L±012g/L, n=7) and/or nonbiliary diseases (027g/L±009g/L, n=10). Pronucleating activities were much stronger in patients with cholesterol gallstones (nucleation time ratio: 057±021, n=5, P<001 vs pigment gallstone and/or nonbiliary diseases) and gallbladder cholesterosis (nucleation time ratio: 044±023, n=5, P<001 vs pigment gallstone or nonbilliary diseases). The binding percentages of CPs to model biliary vesicles were also higher in patients with cholesterol gallstones (n=6) than those with pigment gallstones (n=6) (24%±09% vs 09%±05%, P<001).CONCLUSION Hypersecretion of CPs, especially those in vesicular phase may be the important changes in the early stage of cholesterol gallstone.
文摘BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2), and multiple drug resistance 3 (MDR3 ) are 3 well-known transporting proteins, their effect on lithogenesis has not been elucidated. This study was undertaken to examine the relationship between BSEP, MRP2, MDR3, and cholesterol calculus formation. METHODS: Liver tissue specimens were taken from 20 patients with cholesterol calculus and from 10 patients with normal liver. mRNA and protein expressions of BSEP, MRP2, and MDR3 were determined by reverse tran-scriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. This study was approved by the ethics committee of China Medical University and informed consent was obtained from all patients. RESULTS: mRNA and protein expressions of BSEP, MRP2, and MDR3 were significantly down-regulated in the liver tissue of the patients with cholesterol calculus compared with normal liver tissue of the controls. CONCLUSION: The down-regulation of BSEP, MRP2, and MDR3 may be correlated with the formation of cholesterol calculus.
基金the Swedish Medical Research Council(03X-4793 and 03X-7890)
文摘AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.
基金Supported by research grants from the Ministry of Economic Affairs of Taiwan,the Republic of China with grant NO.98-EC-17-A-17-S1-132
文摘Objective:To evaluate the ability of lactic acid bacteria(LAB)strains isolated from fermented mustard to lower the cholesterol in vitro.Methods:The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method.The LAB isolates were analyzed for their resistance to acid and bile salt.Strains with lowering cholesterol activity,were determined adherence to Caco-2 cells.Results:Strain B0007,B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC17010.The isolated strains showed tolerance to pH 3.0 for 3h despite variations in the degree of viability and bile-tolerant strains,with more than 10~s CFU/mL after incubation for 24 h at 1%oxigall in MRS.In addition,strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines.Conclusions:These strains B0007 and B0022 may be potential functional sources for cholesterollowering activities as well as adhering to Caco-2 cell lines.
文摘Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 days. In male rats, body weight gained, and the levels of total lipids, total cholesterol and triglycerides in the liver were significantly decreased as the dose of capsaicinoids increased. On the other hand, plasma total cholesterol (TC), triglycerides (TG), HDL- and LDL-cholesterol concentration and liver weight were not affected by capsaicinoids. While in female rats, plasma TC, TG, HDL-C and LDL-C concentration, liver total lipids, TC and TG concentration were significantly decreased as the dose of capsaicinoids increased. The mRNA level of hepatic TRPV1, ileac ASBT and IBABP were increased as the dose of capsaicinoids increased in all rats groups. The mRNA level of hepatic HMG-CoA reductase, CYP7A1 and FXR were significantly decreased in female rats groups. These results show that the hypocholesterolemic effect of capsaicinoids in dose-dependent manner in rats was mediated by inhibited synthesis of endogenous cholesterol, female rats were more sensitive than male rats on hypolipidemic effect of capsaicinoids.
文摘In the present study, 20 selected Lactobacillus strains already characterized in a previous research for their capability to grow in conditions simulating the intestinal environment, their resistance to antibiotics, their antibacterial activity and their adhesion capability to intestinal human Caco-2 TC7 and HT-29 MTX cell lines, were further investigated to explore more their probiotic properties. Growth behaviour in the presence of prebiotic (fructooligosac-charides (FOS) and lactulose) at a concentration of 2%, cholesterol removal by measuring the residual cholesterol in medium supplemented with cholesterol, ability to deconjugate bile salts using BSH enzyme and antioxidant activity of culture supernatant of Lactobacillus strains by ABTS·+ and DPPH methods were analyzed. All probiotic strains demonstrated important prebiotic assimilation (P > 0.05) even with OD600 > 3 after 30 h of contact, cholesterol removal ability with maximum percentage of 57% after 24 h of contact and they were found to liberate significantly (P < 0.05) more cholic acid with maximum of 0.40 mM of sodium glycocholate, 0.33 mM of sodium taurocholate and 0.41 mM of their mixte and scavenge both radicals with 52% and 2.19% of ABTS·+ and DPPH respectively. This study confirmed the suitability of these probiotic strains for application in functional food formulations especially where cholesterol reduction and antioxidant activity in food are needed to assess possible in vivo human health benefits.
文摘目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附属医院纳入正常及脾虚痰浊血脂异常受试者共计180例,按照就诊顺序随机分为正常组、模型组、健脾祛痰方组,每组60例。所有组别均予健康宣教,健脾祛痰方组予健脾祛痰方颗粒剂冲服,治疗疗程为2个月。采用全自动分析仪检测所有受试者血清胆固醇(Total Cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low Density Lipoprotein,LDL-C)、高密度脂蛋白胆固醇(High Density Lipoprotein,HDL-C)水平,用中医证候积分量表评定患者中医证候疗效,酶联免疫吸附测定法测定受试者血清人成纤维细胞生长因子19(FGF19)的表达水平,16SrRNA高通量测序技术检测受试者粪便标本肠道菌群的结构变化。结果脾虚痰浊型血脂异常患者经健脾祛痰方治疗后血脂水平,中医证候积分较治疗前明显改善,血清中FGF19含量明显降低;健脾祛痰方组血脂疗效、中医证候积分总有效率显著优于模型组。高脂人群菌群多样性和物种丰度与正常人群相比明显减弱。有益菌减少,肠杆菌过生长,肠道菌群结构被破坏。健脾祛痰方组患者用药后样本间差异明显,各分类水平物种组成比例发生变化,编码胆盐水解酶(Bile Salt Hydrolase,BSH)相关微生物丰度降低。用药后肠道中的有害菌肠杆菌目(Enterobacteriales)减少,肠道菌群平衡有所恢复。结论健脾祛痰法能够显著降低血脂异常患者TC、TG、LDL-C水平,改善中医证候,其机制可能通过调节肠道菌群和胆汁酸代谢抑制FXR信号传导通路以降脂。