Objective: To explore the effect of Cangfudaotan Tang on phlegm dampness type of PCOS and the role of oatp2b1 in transportation and transformation of phlegm dampness. Methods: 36 SD female rats were randomly divided i...Objective: To explore the effect of Cangfudaotan Tang on phlegm dampness type of PCOS and the role of oatp2b1 in transportation and transformation of phlegm dampness. Methods: 36 SD female rats were randomly divided into three groups: blank control group, model group and Cangfudaotan Tang group, 12 cases in each one. After PCOS rat models were made, rats of Cangfudaotan Tang group were treated with Cangfudaotan Tang (1.42 g/kg/d) by intragastric administration for 14 days;blank control and model group were given with isodose saline. The expression of oatp2b1 mRNA/Protein in liver and kidney tissues was measured and the level of testosterone (T), follicle stimulating hormone(FSH), estradiol (E<sub>2</sub>), luteinizing hormone(LH), Serum total cholesterol (TG), Triacylglycerols (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were detected at the same time. Results: Compared with blank control group, the expression of oatp2b1 mRNA and the level of TC, TG, LDL, LH, FSH, T in model group were significantly increased (P < 0. 05), while the level of HDL was significantly decreased (P < 0. 05);compared with model group, the expression of oatp2b1 mRNA and the level of TC, TG, LDL in Cangfudaotan Tang group were significantly lowered (P < 0.05);the level of HDL was significantly higher;the oatp2b1 protein in kidney and liver tissues had different degrees of expression, while there was no statistical significance among the three groups. Conclusions: Oatp2b1 might be one of the material bases participating in transportation and transformation of phlegmy dampness. The mechanism of Cangfudaotan Tang treating phlegm dampness type of PCOS may be achieved by regulating the expression of oatp2b1.展开更多
Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipient...Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-展开更多
目的:了解原发性先天性青光眼患者致病基因CYP1B1(Cytochrome P450 family 1 subfamily B polypeptide 1)的变异情况。方法:采用高分辨率熔解(high-resolution melting,HRM)方法,分析20例原发性先天性青光眼患者的CYP1B1基因热点突变区...目的:了解原发性先天性青光眼患者致病基因CYP1B1(Cytochrome P450 family 1 subfamily B polypeptide 1)的变异情况。方法:采用高分辨率熔解(high-resolution melting,HRM)方法,分析20例原发性先天性青光眼患者的CYP1B1基因热点突变区,同时采用测序的方法验证HRM的检测结果。结果:检出g.6767C>T(p.D449D)变异2例,g.2527C>G(p.R48G)变异1例,两种变异共存者1例。结论:在CYP1B1基因突变筛查方法中,HRM具有高度的灵敏性和特异性,可用于筛查原发性先天性青光眼。PCG的原因可能与g.6767C>T(p.D449D)和g.2527C>G(p.R48G)的变异有关;两种变异共存者可能导致更严重的PCG。展开更多
The aim of this study is to evaluate the efficacy of total saponins of Dioscorea（TSD）, an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia mode...The aim of this study is to evaluate the efficacy of total saponins of Dioscorea（TSD）, an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups： model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid（UA）, blood urea nitrogen（BUN）, serum creatinine（Scr）, and organic anion transporting polypeptide 1A1（OATP1A1） levels were measured. Comparison between the model group and treatment（allopurinol and TSD） groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.展开更多
AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the preval...AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null.展开更多
Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pa...Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.展开更多
文摘Objective: To explore the effect of Cangfudaotan Tang on phlegm dampness type of PCOS and the role of oatp2b1 in transportation and transformation of phlegm dampness. Methods: 36 SD female rats were randomly divided into three groups: blank control group, model group and Cangfudaotan Tang group, 12 cases in each one. After PCOS rat models were made, rats of Cangfudaotan Tang group were treated with Cangfudaotan Tang (1.42 g/kg/d) by intragastric administration for 14 days;blank control and model group were given with isodose saline. The expression of oatp2b1 mRNA/Protein in liver and kidney tissues was measured and the level of testosterone (T), follicle stimulating hormone(FSH), estradiol (E<sub>2</sub>), luteinizing hormone(LH), Serum total cholesterol (TG), Triacylglycerols (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were detected at the same time. Results: Compared with blank control group, the expression of oatp2b1 mRNA and the level of TC, TG, LDL, LH, FSH, T in model group were significantly increased (P < 0. 05), while the level of HDL was significantly decreased (P < 0. 05);compared with model group, the expression of oatp2b1 mRNA and the level of TC, TG, LDL in Cangfudaotan Tang group were significantly lowered (P < 0.05);the level of HDL was significantly higher;the oatp2b1 protein in kidney and liver tissues had different degrees of expression, while there was no statistical significance among the three groups. Conclusions: Oatp2b1 might be one of the material bases participating in transportation and transformation of phlegmy dampness. The mechanism of Cangfudaotan Tang treating phlegm dampness type of PCOS may be achieved by regulating the expression of oatp2b1.
文摘Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-
文摘目的:了解原发性先天性青光眼患者致病基因CYP1B1(Cytochrome P450 family 1 subfamily B polypeptide 1)的变异情况。方法:采用高分辨率熔解(high-resolution melting,HRM)方法,分析20例原发性先天性青光眼患者的CYP1B1基因热点突变区,同时采用测序的方法验证HRM的检测结果。结果:检出g.6767C>T(p.D449D)变异2例,g.2527C>G(p.R48G)变异1例,两种变异共存者1例。结论:在CYP1B1基因突变筛查方法中,HRM具有高度的灵敏性和特异性,可用于筛查原发性先天性青光眼。PCG的原因可能与g.6767C>T(p.D449D)和g.2527C>G(p.R48G)的变异有关;两种变异共存者可能导致更严重的PCG。
基金supported by grants from the National Natural Science Foundation of China(No.81072806,and No.81373500)Natural Science Foundation of Guangdong Province(No.S2012010009277)Traditional Chinese Medicine Bureau of Guangdong Province(No.20141046)
文摘The aim of this study is to evaluate the efficacy of total saponins of Dioscorea（TSD）, an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups： model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid（UA）, blood urea nitrogen（BUN）, serum creatinine（Scr）, and organic anion transporting polypeptide 1A1（OATP1A1） levels were measured. Comparison between the model group and treatment（allopurinol and TSD） groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.
基金Supported by Instituto de Salud Carlos Ⅲ,No.PI14/01416 and No.PI15/00856cofinanced by the European Regional Development Fund(ERDF)the Gilead Fellowship Program,No.GLD14-00296
文摘AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null.
基金Supported by Grants from FONCYT(PICT 2007,No.00966, PICT 2010,No.2127)CONICET(PIP 2009-2011,No.1665, PIP2012-2015,No.00014)UNR PID(2008-2011/2012-2015)
文摘Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.
