In this paper, the roles of infrastructure development and transportation coordination for Northeast Asian economic cooperation are discussed. It would be necessary to establish an efficient transportation network as ...In this paper, the roles of infrastructure development and transportation coordination for Northeast Asian economic cooperation are discussed. It would be necessary to establish an efficient transportation network as soon as possible. 'Hub-and-Spoke'transportation system and China-Korean peninsula railway container transportation system might be more significant for regional economic cooperation.展开更多
BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome(SOS)in patients with colorectal cancer liver metastases and increases posto-perative morbidity and mortality.AIM To evaluate T1 map...BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome(SOS)in patients with colorectal cancer liver metastases and increases posto-perative morbidity and mortality.AIM To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging(MRI)for diagnosis of hepatic SOS induced by monocrotaline.METHODS Twenty-four mice were divided into control(n=10)and experimental(n=14)groups.The experimental groups were injected with monocrotaline 2 or 6 days before MRI.MRI parameters were:T1 relaxation time before enhancement;T1 relaxation time 20 minutes after enhancement(T_(1post));a reduction in T1 relaxation time(△T_(1)%);and first enhancement slope percentage of the liver parenchyma(ESP).Albumin and bilirubin score was determined.Histological results served as a reference.Liver parenchyma samples from the control and experimental groups were analyzed by western blotting,and organic anion transporter polypeptide 1(OATP1)was measured.RESULTS T_(1post),△T_(1)%,and ESP of the liver parenchyma were significantly different between two groups(all P<0.001)and significantly correlated with the total histological score of hepatic SOS(r=-0.70,0.68 and 0.79;P<0.001).△T_(1)%and ESP were positively correlated with OATP1 levels(r=0.82,0.85;P<0.001),whereas T_(1post) had a negative correlation with OATP1 levels(r=-0.83;P<0.001).INTRODUCTION Hepatic sinusoidal obstruction syndrome(SOS)is also known as hepatic veno-occlusive disease of the liver[1].The main pathological feature of hepatic SOS is damage to liver terminal vessels,and the clinical symptoms of it include ascites and abdominal pain[2].It was first proposed in 1979 as an early complication of hematopoietic stem cell transplantation[3].The prevalence ranges from 5%to 60%,and hepatic SOS is a potentially severe complication and can even lead to death in severe cases[4].Recently,systemic neoadjuvant chemotherapy became widely regarded as one of the causes hepatic SOS in the patients with advanced metastatic colorectal cancer[5,6],especially those were treated with oxaliplatin[7,8].Oxaliplatin-based preoperative chemotherapy is used for patients with colorectal liver metastases as the standard regimen[8,9],because it could improve tumor resection outcome by shrinking the metastatic sites and reducing recurrence rate[10].Nevertheless,chemotherapy-induced hepatic SOS has been associated with a higher risk of postresection morbidity[11],such as intraoperative bleeding,intraoperative transfusions,and postoperative liver failure[12].Therefore,it is important to detect and diagnose of hepatic SOS timely.Currently,the gold standard is still based on liver biopsy[13],but it is an invasive procedure and has several limitations and complications,such as hemorrhage[14].A noninvasive diagnostic modality is needed for the assessment of hepatic SOS.Some noninvasive tools have been used for diagnosis of hepatic SOS.Researchers have utilized a preoperative platelet count and aspartate aminotransferase to platelet ratio index[15].In addition,some imaging methods such as shear wave ultrasonography,computed tomography,and gadoxetic acid-enhanced magnetic resonance imaging(MRI)have been promoted as useful methods for evaluation of hepatic SOS[16-18].Recent studies with monocrotaline(MCT)-treated rats were conducted to investigate diagnosis and prediction of severity of SOS.For example,intravoxel incoherent motion diffusion-weighted imaging,non-Gaussian diffusion models,and T1 rho quantification[19,20].The MCT-induced hepatic SOS animal model was reproducible,with a detailed pathological scoring criteria[21].Gadoxetic acid is a hepatocyte-specific contrast substance,which can provide parenchymal contrast in the hepato-biliary phase.It is reported that gadoxetic acid is absorbed into the liver parenchyma via organic anion transporter polypeptide 1(OATP1)on the hepatocyte membranes[22-24].Recently,several authors have described the feasibility of gadoxetic acid-enhanced MRI for the diagnosis of oxaliplatin-induced hepatic SOS[25].They mainly diagnosed hepatic SOS based on the signal intensity of the hepatobiliary specific phase.However,there were several limitations due to the inconsistency between signal intensity of the liver parenchyma and the concentration of contrast agent for evaluation of the degree of hepatic SOS[26].Therefore,we measured T1 relaxation time on parametric mapping because it is linearly related to the concentration of the contrast agent and is not affected by other factors[27].Yang et al[28]demonstrated T1 mapping on gadoxetic acid-enhanced MRI for the assessment of oxaliplatin-induced liver injury in a C57BL/6 mouse model.However,the main pathological changes in their model were hepatocyte degeneration and fibrosis.Therefore,we aimed to explore the effectiveness of T1 mapping based on gadoxetic acid-enhanced MRI for the diagnosis of hepatic SOS in a C57BL/6 mouse model,as well as a possible relation between OATP1 Levels and MRI parameters.展开更多
AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A to...AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A total of 61 patients with Crohn＇s disease （CD）, 151 patients with ulcerative colitis （UC）, and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction （PCR-SSP） or by restriction fragment length polymorphism （PCR-RFLP） analysis. RESULTS： Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 （0/61 with CD） and 1.3% （2/151 with UC）. CONCLUSION： Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.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
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 investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). MET...AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.展开更多
OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The mode...OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The model of hyperuricemic mice was induced by intraperitoneal injection of potassium oxonate(250 mg·kg^(-1))for 7 d.Water extracts of Wudang cherry at 500 mg·kg^(-1)were orally administered to hyperuricemic mice for 7 d,benzbromarone(20 mg·kg^(-1))and allopurinol(20 mg·kg^(-1))were given as positive controls,vehicle control group was given equal normal saline.Serum and urine levels of uric acid were measured in hyperuricemic and normal mice.Simultaneously,the m RNA and protein levels of mouse urate transporter 1(m URAT1),glucose transporter 9(mGLUT9),organic anion transporters(mOAT1 and mOAT3),ATP-binding cassette,subfamily G,membrane 2(mABCG2)and organic cation/carnitine transporters(m OCT1,m OCT2,m OCTN1 and m OCTN2)in the kidney were analyzed by Western blot,RT-PCR,immunohistochemical and immunofluorescent assay,respectively.RESULTS Wudang cherry significantly reduced serum uric acid levels and increased urine uric acid levels in hyperuricemic mice.And it effectively reversed potassium oxonate-induced alterations in renal m URAT1,mGLUT9,mOAT1,mOAT3 and mABCG2 m RNA and protein levels,resulting in the enhancement of renal urate excretion in mice.Moreover,Wudang Cherry increased renal m OCT1,m OCT2,m OCTN1 and m OCTN2 m RNA and protein levels,and improved renal impairment in this model.CONCLUSION Wudang cherry processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic mice.展开更多
MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte...MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].展开更多
Surface sediments from the Changjiang River （Yangtze River） Estuary, Hangzhou Bay, and their adjacent waters were analyzed for their grain size distribution, organic carbon （OC） concentration, and stable carbon is...Surface sediments from the Changjiang River （Yangtze River） Estuary, Hangzhou Bay, and their adjacent waters were analyzed for their grain size distribution, organic carbon （OC） concentration, and stable carbon isotope composition （δ13C）. Based on this analysis, about 36 surface sediment samples were selected from various environments and separated into sand （〉0.250 ram, 0.125-0.250 ram, 0.063-0.125 mm） and silt （0.025-0.063 mm） fractions by wet-sieving fractionation methods, and further into silt- （0.004-0.025 mm） and clay-sized （〈0.004 mm） fractions by centrifugal fractionation. Sediments of six grain size categories were analyzed for their OC and 613C contents to explore the grain size composition and transport paths of sedimentary OC in the study area. From fine to coarse fractions, the OC content was 1.18%, 0.51%, 0.46%, 0.42%, 0.99%, and 0.48%, respectively, while the δ13C was -21.64‰, -22.03‰, -22.52‰, -22.46‰, -22.36‰, and -22.28%0, respectively. In each size category, the OC contribution was 42.96%, 26.06%, 9.82%, 5.75%, 7.09%, and 8.33%, respectively. The OC content in clay and fine silt fractions （〈0.025 ram） was about 69.02%. High OC concentrations were mainly found in offshore modern sediments in the northeast of the Changjiang River Estuary, in modern sediments in the lower estuary of the Changjiang River and Hangzhou Bay, and in Cyclonic Eddy modern sediments to the southwest of the Cheju Island. Integrating the distribution of terrestrial OC content of each grain size category with the δ13C of the bulk sediment indicated that the terrestrial organic material in the Changjiang River Estuary was transported seaward and dispersed to the Cyclonic Eddy modern sediments to the southwest of the Cheju Island via two pathways： one was a result of the Changjiang River Diluted Water （CDW） northeastward extending branch driven by the North Jiangsu Coastal Current and the Yellow Sea Coastal Current, while the other one was the result of the CDW southward extending branch driven by the Taiwan Warm Current.展开更多
GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address th...GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.展开更多
Stable carbon isotope ratios have been used to study the sources of particulate organic carbon(POC) in the Amazon River and its tributaries, and to examine the transport of the riverine POC intothe oceanic environment...Stable carbon isotope ratios have been used to study the sources of particulate organic carbon(POC) in the Amazon River and its tributaries, and to examine the transport of the riverine POC intothe oceanic environment. POC in the upper reaches of the Amazon River has more positive δC values(--24.5‰ to -- 28.0‰) than that in the middle and lower reaches (--27.9‰ to -- 30.1‰). TheδC of POC from the tributaries is generally more negative than that observed in the Amazon mainchannel. This δC datum shows that the POC in the Amazon main channel is predominantly of terres-trial origin rather than a result of in situ production. A large range of δC values (--17.5‰ to -28.4‰) is observed in the Amazon Estuary and plume. and is considered as the result of the mixing展开更多
AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile a...AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decreased 2.7-fold,whereas it increased 1.7-fold in those on CY diet compared to C diet fed groups. CONCLUSION: These data demonstrate that expression of ASBT and t-ASBT in cholangiocytes is regulated by a negative feedback loop while the expression of these transporters in terminal ileum is modified via positive feedback.Thus, while transcriptional regulatory mechanisms in response to alterations in bile acid pool size are operative in both cholangiocytes and ileocytes,each cell type responds differently to bile acid supplementation and depletion.展开更多
AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion...AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion transporter 1 （OAT1）, OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 （OCTN1） and OCTN2, were over-expressed in human embryonic kidney （HEK）-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors （ranged from 0.0001 to 50 μmol/L） were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value （the concentration that inhibits 50% of the transporter function） of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS： Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate （ES） mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L （P 〈 0.01） for apigenin and kaempferol, respectively.CONCLUSION： Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.展开更多
A series of star-shaped molecules with benzene core and naphthalimides derivatives end groups have been designed to explore their optical,electronic,and charge transport properties as charge transport and/or luminesce...A series of star-shaped molecules with benzene core and naphthalimides derivatives end groups have been designed to explore their optical,electronic,and charge transport properties as charge transport and/or luminescent materials for organic light-emitting diodes（OLEDs）. The frontier molecular orbitals（FMOs） analysis has turned out that the vertical electronic transitions of absorption and emission are characterized as intramolecular charge transfer（ICT）. The calculated results show that the optical and electronic properties of star-shaped molecules are affected by the substituent groups in N-position of 1,8-naphthalimide ring. Our results suggest that star-shaped molecules with n-butyl（1）,benzene（2）,thiophene（3）,thiophene S？,S？-dioxide（4）,benzo[c][1,2,5]thiadiazole（5）,and 2,7a-dihydrobenzo[d]thiazole（6） fragments are expected to be promising candidates for luminescent and electron transport materials for OLEDs. This study should be helpful in further theoretical investigations on such kind of systems and also to the experimental study for charge transport and/or luminescent materials for OLEDs.展开更多
BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane tr...BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane transport effects.AIM To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance.METHODS Twelve adult rats were included in this study;baseline hepatic and renal laboratory values and digoxin pharmacokinetic(PK)studies were established before evenly dividing them into two groups to undergo bile duct ligation(BDL)or a sham procedure.After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction.Data were analyzed using SigmaStat 3.5.Means between pre-surgery and post-surgery in the same experimental group were compared by paired t-test,while independent t-test was employed to compare the means between sham and BDL groups.RESULTS Digoxin clearance was decreased and liver function,but not renal function,was impaired in BDL rats.BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine.Organic anion transporting polypeptides(OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL.OATP4C1 expression was markedly increased in the kidney following BDL.CONCLUSION The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis.These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.展开更多
We demonstrate that the electroluminescent performances of organic light-emitting diodes are significantly improved by employing a zinc phthalocyanine （ZnPc）-based composite hole transport layer （c-HTL）. The optim...We demonstrate that the electroluminescent performances of organic light-emitting diodes are significantly improved by employing a zinc phthalocyanine （ZnPc）-based composite hole transport layer （c-HTL）. The optimum ris-（8-hydroxyquinoline）aluminum （Alq3）-based organic light-emitting diode with a c-HTL exhibits a lower turn-on voltage of 2.8 V, a higher maximum current efficiency of 3.40 cd/A and a higher maximum power efficiency of 1.91 lm/W, which are superior to those of the conventional device （turn-on voltage of 3.8 V, maximum current efficiency of 2.60 cd/A, and maximum power efficiency of 1.21 lm/W）. We systematically studied the effects of different kinds of N’-diphenyl-N,N’-bis（1-naphthyl）（1,1’-biphenyl）-4,4’diamine （NPB）：ZnPc c-HTL. Meanwhile, we also investigate their mechanisms different from that in the case of using ZnPc as buffer layer. The specific analysis is based on the absorption spectra of the hole transporting material and current density–voltage characteristics of the corresponding hole-only devices.展开更多
Purpose–Under the dual pressure of resources and environment,many countries have focused on the role of railways in promoting low-carbon development of integrated transportation and of even the whole society.This pap...Purpose–Under the dual pressure of resources and environment,many countries have focused on the role of railways in promoting low-carbon development of integrated transportation and of even the whole society.This paper aims to provide a comprehensive study on methods to improve railway energy efficiency in other national railways and achievements made by China’s railways in the past practice,and then to propose ways in which in the future China’s railways could rationally select the path of improving energy efficiency regarding the needs of the nation’s ever-shifting development and carry out the re-engineering for mechanism innovation in energy conservation and emission reduction process.Design/methodology/approach–This paper first studies other national railways that have tried to promote the improvement of railway energy efficiency by the ways of technology,management and structural reconstruction to reduce energy consumption and carbon emissions.Among them,the effect of structural energy conservation and emission reduction has become more prominent.It has become the main energy conservation and emission reduction measure adopted by foreign railway sectors.The practice of energy conservation and emission reduction of railways in various countries has tended to shift from a technical level to a structural one.Findings–Key aspects in improving energy efficiency include re-optimization of energy structure,reinnovation of energy-saving technologies and optimization of transportation organization.Path selection includes continuing to promote electrified railway construction,increasing the use of new and renewable energy sources,and promoting the reform of railway transportation organizations.Originality/value–This paper provides further challenges and research directions in the proposed area and has referential value for the methodologies,approaches for practice in a Chinese context.To achieve the expected goals,relevant supporting policies and measures need to be formulated,including actively guiding integrated transportation toward railway-oriented development,promoting innovation in energy-saving and emission reduction mechanisms and strengthening policy incentives,focusing on improving the energy efficiency of railways through market behavior.At the same time,it is necessary to pay attention to new phenomena in the railway industry for track and analysis.展开更多
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
Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal...Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.展开更多
基金Under the auspices of the National Natural Science Foundation of China (No. 49871026) key Directional Project of Knowledge Inno
文摘In this paper, the roles of infrastructure development and transportation coordination for Northeast Asian economic cooperation are discussed. It would be necessary to establish an efficient transportation network as soon as possible. 'Hub-and-Spoke'transportation system and China-Korean peninsula railway container transportation system might be more significant for regional economic cooperation.
基金the National Science Foundation for Young Scientists of China,No.81701682.
文摘BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome(SOS)in patients with colorectal cancer liver metastases and increases posto-perative morbidity and mortality.AIM To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging(MRI)for diagnosis of hepatic SOS induced by monocrotaline.METHODS Twenty-four mice were divided into control(n=10)and experimental(n=14)groups.The experimental groups were injected with monocrotaline 2 or 6 days before MRI.MRI parameters were:T1 relaxation time before enhancement;T1 relaxation time 20 minutes after enhancement(T_(1post));a reduction in T1 relaxation time(△T_(1)%);and first enhancement slope percentage of the liver parenchyma(ESP).Albumin and bilirubin score was determined.Histological results served as a reference.Liver parenchyma samples from the control and experimental groups were analyzed by western blotting,and organic anion transporter polypeptide 1(OATP1)was measured.RESULTS T_(1post),△T_(1)%,and ESP of the liver parenchyma were significantly different between two groups(all P<0.001)and significantly correlated with the total histological score of hepatic SOS(r=-0.70,0.68 and 0.79;P<0.001).△T_(1)%and ESP were positively correlated with OATP1 levels(r=0.82,0.85;P<0.001),whereas T_(1post) had a negative correlation with OATP1 levels(r=-0.83;P<0.001).INTRODUCTION Hepatic sinusoidal obstruction syndrome(SOS)is also known as hepatic veno-occlusive disease of the liver[1].The main pathological feature of hepatic SOS is damage to liver terminal vessels,and the clinical symptoms of it include ascites and abdominal pain[2].It was first proposed in 1979 as an early complication of hematopoietic stem cell transplantation[3].The prevalence ranges from 5%to 60%,and hepatic SOS is a potentially severe complication and can even lead to death in severe cases[4].Recently,systemic neoadjuvant chemotherapy became widely regarded as one of the causes hepatic SOS in the patients with advanced metastatic colorectal cancer[5,6],especially those were treated with oxaliplatin[7,8].Oxaliplatin-based preoperative chemotherapy is used for patients with colorectal liver metastases as the standard regimen[8,9],because it could improve tumor resection outcome by shrinking the metastatic sites and reducing recurrence rate[10].Nevertheless,chemotherapy-induced hepatic SOS has been associated with a higher risk of postresection morbidity[11],such as intraoperative bleeding,intraoperative transfusions,and postoperative liver failure[12].Therefore,it is important to detect and diagnose of hepatic SOS timely.Currently,the gold standard is still based on liver biopsy[13],but it is an invasive procedure and has several limitations and complications,such as hemorrhage[14].A noninvasive diagnostic modality is needed for the assessment of hepatic SOS.Some noninvasive tools have been used for diagnosis of hepatic SOS.Researchers have utilized a preoperative platelet count and aspartate aminotransferase to platelet ratio index[15].In addition,some imaging methods such as shear wave ultrasonography,computed tomography,and gadoxetic acid-enhanced magnetic resonance imaging(MRI)have been promoted as useful methods for evaluation of hepatic SOS[16-18].Recent studies with monocrotaline(MCT)-treated rats were conducted to investigate diagnosis and prediction of severity of SOS.For example,intravoxel incoherent motion diffusion-weighted imaging,non-Gaussian diffusion models,and T1 rho quantification[19,20].The MCT-induced hepatic SOS animal model was reproducible,with a detailed pathological scoring criteria[21].Gadoxetic acid is a hepatocyte-specific contrast substance,which can provide parenchymal contrast in the hepato-biliary phase.It is reported that gadoxetic acid is absorbed into the liver parenchyma via organic anion transporter polypeptide 1(OATP1)on the hepatocyte membranes[22-24].Recently,several authors have described the feasibility of gadoxetic acid-enhanced MRI for the diagnosis of oxaliplatin-induced hepatic SOS[25].They mainly diagnosed hepatic SOS based on the signal intensity of the hepatobiliary specific phase.However,there were several limitations due to the inconsistency between signal intensity of the liver parenchyma and the concentration of contrast agent for evaluation of the degree of hepatic SOS[26].Therefore,we measured T1 relaxation time on parametric mapping because it is linearly related to the concentration of the contrast agent and is not affected by other factors[27].Yang et al[28]demonstrated T1 mapping on gadoxetic acid-enhanced MRI for the assessment of oxaliplatin-induced liver injury in a C57BL/6 mouse model.However,the main pathological changes in their model were hepatocyte degeneration and fibrosis.Therefore,we aimed to explore the effectiveness of T1 mapping based on gadoxetic acid-enhanced MRI for the diagnosis of hepatic SOS in a C57BL/6 mouse model,as well as a possible relation between OATP1 Levels and MRI parameters.
基金Doctoral Natural Science Fund of Guangdong Province, China, No. 04300361
文摘AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A total of 61 patients with Crohn＇s disease （CD）, 151 patients with ulcerative colitis （UC）, and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction （PCR-SSP） or by restriction fragment length polymorphism （PCR-RFLP） analysis. RESULTS： Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 （0/61 with CD） and 1.3% （2/151 with UC）. CONCLUSION： Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.
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.
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.
文摘AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
基金supported by National Natural Science Foundation of China(81402994)Natural Science Foundation of Hubei Province(2014CFB652)"2011 Plan" Open Fund Innovation Team Project of Hubei Province(2011JH-2014CXTT08)
文摘OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The model of hyperuricemic mice was induced by intraperitoneal injection of potassium oxonate(250 mg·kg^(-1))for 7 d.Water extracts of Wudang cherry at 500 mg·kg^(-1)were orally administered to hyperuricemic mice for 7 d,benzbromarone(20 mg·kg^(-1))and allopurinol(20 mg·kg^(-1))were given as positive controls,vehicle control group was given equal normal saline.Serum and urine levels of uric acid were measured in hyperuricemic and normal mice.Simultaneously,the m RNA and protein levels of mouse urate transporter 1(m URAT1),glucose transporter 9(mGLUT9),organic anion transporters(mOAT1 and mOAT3),ATP-binding cassette,subfamily G,membrane 2(mABCG2)and organic cation/carnitine transporters(m OCT1,m OCT2,m OCTN1 and m OCTN2)in the kidney were analyzed by Western blot,RT-PCR,immunohistochemical and immunofluorescent assay,respectively.RESULTS Wudang cherry significantly reduced serum uric acid levels and increased urine uric acid levels in hyperuricemic mice.And it effectively reversed potassium oxonate-induced alterations in renal m URAT1,mGLUT9,mOAT1,mOAT3 and mABCG2 m RNA and protein levels,resulting in the enhancement of renal urate excretion in mice.Moreover,Wudang Cherry increased renal m OCT1,m OCT2,m OCTN1 and m OCTN2 m RNA and protein levels,and improved renal impairment in this model.CONCLUSION Wudang cherry processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic mice.
基金supported by"H+Die Spitaler der Schweiz" the Swiss Agency for Development and Cooperation(DEZA)by the University Hospital Zurich/Switzerland
文摘MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].
基金The National Basic Research Program(973 Program)of China under contract No.2010CB428903the National Natural Science Foundation of China under contract Nos 41106050,41203085 and 41076036+1 种基金the Public Welfare Industry Research Specific Funding of China under contract Nos 201105014,201105012 and 201205008the Basic Scientific Research Fund of the Second Institute of Oceanography of State Oceanic Administration of China under contract Nos JG1108 and JG1219
文摘Surface sediments from the Changjiang River （Yangtze River） Estuary, Hangzhou Bay, and their adjacent waters were analyzed for their grain size distribution, organic carbon （OC） concentration, and stable carbon isotope composition （δ13C）. Based on this analysis, about 36 surface sediment samples were selected from various environments and separated into sand （〉0.250 ram, 0.125-0.250 ram, 0.063-0.125 mm） and silt （0.025-0.063 mm） fractions by wet-sieving fractionation methods, and further into silt- （0.004-0.025 mm） and clay-sized （〈0.004 mm） fractions by centrifugal fractionation. Sediments of six grain size categories were analyzed for their OC and 613C contents to explore the grain size composition and transport paths of sedimentary OC in the study area. From fine to coarse fractions, the OC content was 1.18%, 0.51%, 0.46%, 0.42%, 0.99%, and 0.48%, respectively, while the δ13C was -21.64‰, -22.03‰, -22.52‰, -22.46‰, -22.36‰, and -22.28%0, respectively. In each size category, the OC contribution was 42.96%, 26.06%, 9.82%, 5.75%, 7.09%, and 8.33%, respectively. The OC content in clay and fine silt fractions （〈0.025 ram） was about 69.02%. High OC concentrations were mainly found in offshore modern sediments in the northeast of the Changjiang River Estuary, in modern sediments in the lower estuary of the Changjiang River and Hangzhou Bay, and in Cyclonic Eddy modern sediments to the southwest of the Cheju Island. Integrating the distribution of terrestrial OC content of each grain size category with the δ13C of the bulk sediment indicated that the terrestrial organic material in the Changjiang River Estuary was transported seaward and dispersed to the Cyclonic Eddy modern sediments to the southwest of the Cheju Island via two pathways： one was a result of the Changjiang River Diluted Water （CDW） northeastward extending branch driven by the North Jiangsu Coastal Current and the Yellow Sea Coastal Current, while the other one was the result of the CDW southward extending branch driven by the Taiwan Warm Current.
基金foundations from Chinese Academy of Sciences and Special Funds for Major State Basic reseaxch of China (G1999053903).
文摘GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.
文摘Stable carbon isotope ratios have been used to study the sources of particulate organic carbon(POC) in the Amazon River and its tributaries, and to examine the transport of the riverine POC intothe oceanic environment. POC in the upper reaches of the Amazon River has more positive δC values(--24.5‰ to -- 28.0‰) than that in the middle and lower reaches (--27.9‰ to -- 30.1‰). TheδC of POC from the tributaries is generally more negative than that observed in the Amazon mainchannel. This δC datum shows that the POC in the Amazon main channel is predominantly of terres-trial origin rather than a result of in situ production. A large range of δC values (--17.5‰ to -28.4‰) is observed in the Amazon Estuary and plume. and is considered as the result of the mixing
文摘AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decreased 2.7-fold,whereas it increased 1.7-fold in those on CY diet compared to C diet fed groups. CONCLUSION: These data demonstrate that expression of ASBT and t-ASBT in cholangiocytes is regulated by a negative feedback loop while the expression of these transporters in terminal ileum is modified via positive feedback.Thus, while transcriptional regulatory mechanisms in response to alterations in bile acid pool size are operative in both cholangiocytes and ileocytes,each cell type responds differently to bile acid supplementation and depletion.
基金Supported by Internal funding from Faculty of Pharmacy,the University of Sydney,Australia
文摘AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion transporter 1 （OAT1）, OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 （OCTN1） and OCTN2, were over-expressed in human embryonic kidney （HEK）-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors （ranged from 0.0001 to 50 μmol/L） were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value （the concentration that inhibits 50% of the transporter function） of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS： Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate （ES） mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L （P 〈 0.01） for apigenin and kaempferol, respectively.CONCLUSION： Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.
基金Support by the National Natural Science Foundation of China(No.21563002)the Natural Science Foundation of Inner Mongolia Autonomous Region(No.2015MS0201)the Research Program of Sciences at Universities of Inner Mongolia Autonomous Region(No.NJZZ235)
文摘A series of star-shaped molecules with benzene core and naphthalimides derivatives end groups have been designed to explore their optical,electronic,and charge transport properties as charge transport and/or luminescent materials for organic light-emitting diodes（OLEDs）. The frontier molecular orbitals（FMOs） analysis has turned out that the vertical electronic transitions of absorption and emission are characterized as intramolecular charge transfer（ICT）. The calculated results show that the optical and electronic properties of star-shaped molecules are affected by the substituent groups in N-position of 1,8-naphthalimide ring. Our results suggest that star-shaped molecules with n-butyl（1）,benzene（2）,thiophene（3）,thiophene S？,S？-dioxide（4）,benzo[c][1,2,5]thiadiazole（5）,and 2,7a-dihydrobenzo[d]thiazole（6） fragments are expected to be promising candidates for luminescent and electron transport materials for OLEDs. This study should be helpful in further theoretical investigations on such kind of systems and also to the experimental study for charge transport and/or luminescent materials for OLEDs.
文摘BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane transport effects.AIM To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance.METHODS Twelve adult rats were included in this study;baseline hepatic and renal laboratory values and digoxin pharmacokinetic(PK)studies were established before evenly dividing them into two groups to undergo bile duct ligation(BDL)or a sham procedure.After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction.Data were analyzed using SigmaStat 3.5.Means between pre-surgery and post-surgery in the same experimental group were compared by paired t-test,while independent t-test was employed to compare the means between sham and BDL groups.RESULTS Digoxin clearance was decreased and liver function,but not renal function,was impaired in BDL rats.BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine.Organic anion transporting polypeptides(OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL.OATP4C1 expression was markedly increased in the kidney following BDL.CONCLUSION The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis.These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.
基金Project supported by the National Key Basic Research and Development Program of China(Grant No.2010CB327701)the National Natural Science Foundation of China(Grant No.61275033)
文摘We demonstrate that the electroluminescent performances of organic light-emitting diodes are significantly improved by employing a zinc phthalocyanine （ZnPc）-based composite hole transport layer （c-HTL）. The optimum ris-（8-hydroxyquinoline）aluminum （Alq3）-based organic light-emitting diode with a c-HTL exhibits a lower turn-on voltage of 2.8 V, a higher maximum current efficiency of 3.40 cd/A and a higher maximum power efficiency of 1.91 lm/W, which are superior to those of the conventional device （turn-on voltage of 3.8 V, maximum current efficiency of 2.60 cd/A, and maximum power efficiency of 1.21 lm/W）. We systematically studied the effects of different kinds of N’-diphenyl-N,N’-bis（1-naphthyl）（1,1’-biphenyl）-4,4’diamine （NPB）：ZnPc c-HTL. Meanwhile, we also investigate their mechanisms different from that in the case of using ZnPc as buffer layer. The specific analysis is based on the absorption spectra of the hole transporting material and current density–voltage characteristics of the corresponding hole-only devices.
文摘Purpose–Under the dual pressure of resources and environment,many countries have focused on the role of railways in promoting low-carbon development of integrated transportation and of even the whole society.This paper aims to provide a comprehensive study on methods to improve railway energy efficiency in other national railways and achievements made by China’s railways in the past practice,and then to propose ways in which in the future China’s railways could rationally select the path of improving energy efficiency regarding the needs of the nation’s ever-shifting development and carry out the re-engineering for mechanism innovation in energy conservation and emission reduction process.Design/methodology/approach–This paper first studies other national railways that have tried to promote the improvement of railway energy efficiency by the ways of technology,management and structural reconstruction to reduce energy consumption and carbon emissions.Among them,the effect of structural energy conservation and emission reduction has become more prominent.It has become the main energy conservation and emission reduction measure adopted by foreign railway sectors.The practice of energy conservation and emission reduction of railways in various countries has tended to shift from a technical level to a structural one.Findings–Key aspects in improving energy efficiency include re-optimization of energy structure,reinnovation of energy-saving technologies and optimization of transportation organization.Path selection includes continuing to promote electrified railway construction,increasing the use of new and renewable energy sources,and promoting the reform of railway transportation organizations.Originality/value–This paper provides further challenges and research directions in the proposed area and has referential value for the methodologies,approaches for practice in a Chinese context.To achieve the expected goals,relevant supporting policies and measures need to be formulated,including actively guiding integrated transportation toward railway-oriented development,promoting innovation in energy-saving and emission reduction mechanisms and strengthening policy incentives,focusing on improving the energy efficiency of railways through market behavior.At the same time,it is necessary to pay attention to new phenomena in the railway industry for track and analysis.
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-
基金supported by the National Natural Science Foundation of China(Nos.82173884,81872930,82073922 and 81872833)the“Double First-Class”university project(No.CPU2018GY22,China)。
文摘Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.
