001) and adenoma (P = 0.03). Tie-2, the tyrosine kinase receptor that binds its ligands Ang-1 and Ang-2, was up-regulated Epacadostat datasheet only in FNH and not in HCA (Fig. 1). At the protein

level, the differences in mRNA could not be substantiated for Ang-1 and Tie-2, whereas Ang-2 protein expression was below the detection limit in western blot analysis. Previously, we were able to demonstrate Ang-2 protein expression in renal cell carcinoma protein extracts,8 and this indicated that the experimental protocol used per se is appropriate for the detection of this protein. In Fig. 2, the cellular localization of Ang-1, Ang-2, and Tie-2 is depicted. In both lesions and normal liver samples, cytoplasmic staining of Ang-1 was observed readily in hepatocytes and less prominently in bile ducts and ductules. Ang-1 was absent in SECs and VECs. Ang-2 was present in SECs and VECs and in bile ducts and ductules, albeit less pronouncedly. In some samples of histologically normal livers and liver tissue adjacent to the lesions, Ang-2 showed a more intense expression in the centrilobular areas. Hepatocytes were negative. Tie-2 expression was strongly positive in SECs and VECs in both types of lesions and in normal livers as well as adjacent liver tissue, whereas

no expression was detected in hepatocytes, Wnt beta-catenin pathway bile ducts, or ductules. Table 2 summarizes the localization patterns observed in the different tissues. In Fig. 3A,B, the results of the quantitative mRNA and protein expression analyses of the VEGF system are shown. In FNH and HCA, no significant alterations occurred in VEGF-A expression at the gene (Fig. 3A) or protein levels (Fig. 3B) in comparison with normal liver samples. Also, when the HCA group was divided into selleck chemicals llc the I-HCA type (the largest subgroup, n = 6) and the noninflammatory type (n = 7), no significant differences

in gene or protein expression levels of VEGF-A could be detected (not shown). The VEGFR-1 gene expression level in FNH and in the liver adjacent to HCA was significantly lower than that in normal samples. No other significant differences in VEGFR-1 expression were observed (Fig. 3A). There were no significant differences in the VEGFR-2 gene expression between normal livers, FNH, and HCA and between lesions and nonlesional counterparts. The cellular localization of VEGF-A and both receptors was studied by immunohistology (Fig. 4). In normal livers, VEGF-A was expressed by SECs, VECs, bile ducts, and ductules, but hepatocytes were negative. In FNH and HCA, a similar cellular distribution was found, except that FNH and HCA did not contain bile ducts, and only I-HCA contained ductules. VEGF-A expression in SECs of HCA was much less intense than that in FNH and normal livers. In the sinusoidal spaces of HCA, VEGF-A was predominantly seen in macrophages. The adjacent liver of FNH and HCA showed a pattern of VEGF-A expression similar to that seen in normal liver samples.

Issues pertaining to the correction of coagulopathy in patients on anticoagulation prior to endoscopy, those with bleeding ulcers on aspirin, as well as the management of high-risk endoscopic lesions, including of adherent clots, and the different available hemostatic modalities Forskolin datasheet and their comparative efficacies are discussed. The characteristics of different pharmacological therapies and, specifically, proton pump inhibitors, including pre-endoscopic use, optimal dosage, and route of administration are also reviewed. In the event of failed endoscopic hemostasis, the respective roles of angiography and surgery are discussed. We conclude by reviewing contemporary international consensus recommendations.

The scope of the review does not cover issues of secondary prophylaxis, however. Although the management of NVUGIB has changed with the advent of endoscopic and pharmacological advances, only recently have data suggested a possible modest drop in mortality rates. “
“The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed

up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by CB-839 solubility dmso hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used

a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 μL serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar learn more peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion. Conclusion: Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;) Hepatocellular carcinoma (HCC) is a common and fatal malignancy with a worldwide occurrence.

c-Src, the

cellular prototype I-BET-762 ic50 of this kinase family, has been originally discovered as the mammalian homologue of viral Src kinase encoded by the Rous sarcoma virus.18, 19 c-Src is ubiquitously expressed and is of particular importance for governing cellular processes associated with cellular proliferation, differentiation, and cell survival such as cell cycle control, protein synthesis, organization of the cytoskeleton, and the cell adhesion network.6, 7 The present study provides evidence that c-Src contributes toward maintenance of HCV replication, as suppression of c-Src expression by specific siRNAs resulted in an effective down-regulation of HCV replication (Fig. 2). Neither Fyn nor Yes was able to annihilate this inhibitory effect of c-Src knockdown on HCV replication.

This suggests that c-Src plays a specific role for HCV replication and cannot be substituted by the two other ubiquitously expressed SFK members Yes and Fyn, a notion that is further supported by the fact that siRNA directed against these two kinases has no influence on HCV replication. In line with this, HCV replication is also highly sensitive toward the protein tyrosine kinase inhibitor herbimycin A (Fig. 1), which has been originally described as an inhibitor of viral Src activity14 and R788 solubility dmso subsequently demonstrated to likewise inhibit c-Src activity.13, 15 Our notion that this effect of herbimycin A on HCV replication is indeed mainly due to the inhibition of c-Src function is further supported by the observation that this website down-regulation of c-Src expression by siRNA is accompanied by a reduction of the IC50 of herbimycin A, which is commensurate to the reduction of c-Src protein levels (Fig. 2D). It has been demonstrated in previous reports that HCV-encoded proteins interact with members of the Src family kinases. Notably, NS5A has been suggested to interact with the SH3 domain of Hck,

Lck, Lyn, and Fyn, but interestingly not with that of c-Src.8, 20 The interaction of NS5A with the respective member of the SFK family was suggested to inhibit the activity of Hck, Lck, and Lyn and enhances activation of Fyn, which in turn resulted in an increased activation of STAT3.8 In contrast to this, a recent report used an siRNA-based screening approach and identified the C-terminal Src kinase, which mediates phosphorylation of the C-terminal inhibitory tyrosine residue of SFKs, to be required for replication. This effect of C-terminal Src kinase was suggested to be due to negative regulation of Fyn,9 because siRNA-mediated suppression of Fyn expression was reported to enhance replication, whereas siRNAs directed against the other ubiquitously expressed SFKs c-Src and Yes were reported to have no effect on replication. In the present study, we were unable to confirm the proposed inhibitory effect of Fyn on HCV replication.

It is also necessary to establish a local reference interval that reflects normalcy. One of the main advantages of the APTT is its

simplicity. It can be performed manually by tilt-tube technique or easily be automated using high throughput analysers. Whilst many countries are still dependent on manual coagulation techniques, automation, whether it be semi or fully automated are slowly becoming the norm. However, technologists should recognize that even with automated equipment they are ultimately in control of its use and maintenance. The following may give emerging countries some guidance on how to approach the transition from manual to automation. Automation in haemostasis is relatively recent. The original techniques used PXD101 manufacturer for coagulation studies were manual methods based on visual detection of the fibrin clot and were the most common form of clot detection

right up to the 1970s when new semi-automatic equipment was invented based on photometric or mechanical principles to detect fibrin. selleck products Because of the increasing demand for high volume, routine coagulation screening tests such as PT, APTT, Clauss fibrinogen (FIB) and an increasing demand of budget management, fully automated coagulation analysers have become more and more popular. These analysers have continued to be developed and as a result have become more sophisticated and coagulation testing results have become

more than just a number expressed in seconds. For instance, modern photo-optical coagulometers collect optical data over the entire course of clot formation in the form of a reaction curve, thus providing additional information through alterations that may affect its shape and slope caused by the activities and reactions of coagulation factors and inhibitors. Automation in a coagulation laboratory: 1 Improves the capacity and flexibility of time spent by a professional. There are basically two methods of end-point clot detection available: 1 Mechanical find more 2.1  Photo-optical These methodologies all have their advantages and disadvantages from the possibility to measure antigen-antibody reactions in proteins to optical checks for haemolysis, lipaemia and icteric samples as well as wave form analyses [19]. For routine assays, most instruments are sold in combination with coagulation reagents that are intended for use on those instruments. The reagents may vary greatly in their degree of sensitivity to detect factor deficiencies and coagulation inhibitors; therefore when selecting an instrument type, a specific instrument-reagent combination should be evaluated [20].

Anam Medical Center Objective: Benexate hydrochloride betadex (BHB) is used as anti-ulcer agent, which is thought to increase blood flow in the gastric mucosa. Anti-infection Compound Library However, the mechanism of pharmacological action that increases blood flow in a gastric mucosa by BHB is not certain. Also, BHB action of inflammation, which is closely related to tissue injury and ulcer healing, were not fully investigated. This study was performed to investigate BHB action of ulcer healing in rat by an enhancement of microcirculation mediated by nitric oxide (NO) and anti-inflammatory activity. Methods: Gastric mucosal injury rat

model was made by injecting 60% acetic acid solution into the stomach. After ulcer induction, rats were randomly allocated to one of the following 4 groups, water; BHB 1000 mg/kg; L-N-nitroarginine methyl ester (L-NAME); BHB and L-NAME.

The rats were orogastrically gavaged with BHB or L-NAME for 5 days, and then sacrificed. We measured the area of gastric ulcers by planimetry and the expression of COX, cytokines, NO synthase (NOS) of stomach tissues by western blot analysis. Results: The size of ulcer lesions decreased in the group treated with BHB as compared with control group. The administration with L-NAME aggravated ethanol-induced mucosal injury. The iNOS and nNOS signals increased in gastric ulcerous mucosa treated with BHB. L-NAME administration significantly decreased the expressions of NOS compared to the control group. The degree of inhibited Tamoxifen purchase eNOS and nNOS levels increased after 70 mg/kg L-NAME + 1000 mg/kg BHB administration. The level of COX-2, IL-1β and TNF-α was significantly decreased in BHB-treated group. Conclusion: These results suggest that BHB as anti-ulcer agent enhances microcirculation and reduces proinflammatory cytokines. BHB could be responsible for protection against acetic acid-induced gastric mucosal injury. Key Word(s): 1. Nitric oxide; 2. Benexate; 3. anti-ulcer agent;

4. cyclooxygenase; Presenting Author: OK-JAE LEE Additional Authors: CHANG-YOON HA, HYUN-JIN KIM Corresponding Author: OK-JAE LEE Affiliations: Gyeong National check details University School of Medicine Objective: Primary non-ampullary duodenal adenocarcinoma is a rare disease with a poorly defined natural history. This study was conducted to evaluate the clinical characteristics of patients with primary duodenal adenocarcinoma and to identify its prognostic factors. Methods: We reviewed retrospectively the medical records of the patients with primary duodenal adenocarcinoma diagnosed at Gyeongsang National University Hospital from January 2000 to September 2012. The demographic and clinico-pathological variables were investigated, and survival with its related factors was analyzed. Results: A total of 22 patients with primary non-ampullary duodenal adenocarcinoma were diagnosed and managed during this period. The median age was 64 ± 15 years and 13 patients were male.

[3] Interestingly, Cbs−/− mice exhibit severe liver injury, steatosis, and fibrosis.[32] In a similar manner, we also investigated the role of PLIN2 on a background of high SAMe. For these studies we generated a novel, double Gnmt−/−/Plin2−/− knockout mouse model that is characterized by high hepatic SAMe and low PE content, much like Gnmt−/− mice, that in contrast did not develop fatty liver. Consistent with previous findings,[12, 13] knockout of Plin2 in GNMT-depleted livers decreased lipogenesis and increased TG secretion. Plin2 ablation increased Ibrutinib gluconeogenesis, indicating that crosstalk exists between lipid synthesis and sequestration

and glucose metabolism. Since PE methylation has been shown to promote LD formation,[26] these results PS-341 datasheet support a model where increased

PEMT activity induces both TG synthesis and its accumulation into newly formed LD. Collectively, these observations, taken in light of previous findings,[5, 6] demonstrate that SAMe regulates liver lipid homeostasis through a concerted series of homeostatic actions that include: activation of lipogenesis and inhibition of TG secretion at low SAMe, and activation of TG synthesis via PEMT at high SAMe. This cascade of events goes a long way towards explaining why a chronic imbalance in hepatic SAMe synthesis,[4] or catabolism,[8] is capable of inducing NAFLD. We thank Virginia Gutiérrez de Juan and Begoña Rodríguez-Iruretagoyena for technical selleck products support and Azucena Castro for discussion; and human and technical support from Unidad de formación e investigación UFI11/20, University of Basque Country. Additional Supporting Information may be found in the online version of this article. “
“An 83-year-old man with hepatocellular carcinoma was found to have a low-echoic and low-density tumor measuring 7.2 cm × 5.6 cm. Caroli’s disease was absent. Clinical diagnosis was intrahepatic cholangiocarcinoma. Three cores of liver biopsy were obtained from the tumor. Histologically, it consisted of

liver cysts, ductal plate malformations, peribiliary glands, hepatocytes, portal tracts and mesenchymal tissue. Apparent features of cirrhosis were not found. The liver cysts were lined by a layer of cuboidal cells with multiple papillary protrusions. The ductal plate malformations resembled fetal ductal plates. The peribiliary glands were seromucous glands. Immunohistochemically, these abnormal ductal structures showed positive reaction to biliary type cytokeratins, namely, cytokeratin (CK)7, CK8, CK18 and CK19. Mucin gene expression showed that these biliary structures are positive for fetal antigen MUC1. MUC6 is also positive in them. Aberrant expression of CD10 was observed in these biliary structures. MUC2, MUC5AC and CDX2 were negative.

This group included, among

others, the regulatory genes CCAAT/enhancer binding protein beta (Cebpb), methyl-CpG binding domain protein 1 (Mbd1), and P450 (cytochrome) oxidoreductase (Por) and genes involved in lipid metabolism such as angiopoietin-like 4 (Angptl4), lipin 1 (Lpin1), and Lpin2 (Supporting Table 3). The pathway analysis of differentially expressed genes revealed that the following Gene Ontology (GO) terms JQ1 order were specific to the Mdr2-KO/FVB strain: regulation of immune response, regulation of cell proliferation, regulation of cell cycle, lipid biosynthesis process, and response to oxidative stress (Table 1). The most interesting and statistically significant genes that were differentially expressed in Mdr2-KO livers from both murine strains are shown in Supporting Tables 2 and 3. The expression of the selected genes in the livers of Mdr2-KO/B6 males at the age of 3 months was validated by reverse-transcription polymerase chain reaction (RT-PCR; Fig. 4C). We confirmed the up-regulation of the defensin beta 1 (Defb1), inhibin beta E (Inhbe), Jun, lectin galactoside-binding Vemurafenib concentration soluble 1 (Lgals1), neurotrophic tyrosine kinase receptor type 2 (Ntrk2), regulator of G-protein signaling 5 (Rgs5), and serine peptidase inhibitor Kazal

type 1 (Spink3) transcripts and the down-regulation of the Lpin1 transcript. Remarkably, the allograft inflammatory factor 1 (Aif1), Cd36, and prostaglandin D2 synthase (Ptgds) genes, which were highly up-regulated in the livers of Mdr2-KO/FVB mice,4 were not differentially expressed in the Mdr2-KO/B6 livers (Fig. 4C). We also tested the expression of the selected immune regulators, which play important roles in shaping the inflammatory response, but they were not detected by the Affymetrix microarrays. We selleck screening library found that for both strains, the expression of the genes tumor necrosis factor α (Tnfa), interleukin-2 (Il-2), and Il-10 was significantly up-regulated in the livers of 3-month-old Mdr2-KO

mice (Fig. 4D). We aimed to validate at the protein level the differential expression of 2 regulatory genes among those 14 genes that were reversely differentially expressed in two Mdr2-KO strains: Lpin1 and Mbd1. The Lpin1 gene encodes Lipin-1, one of the key regulators of lipid metabolism.12 The relevance of alterations in lipid metabolism for the pathogenesis and progression of chronic liver disease in Mdr2-KO mice was recently demonstrated.13 The expression patterns of Lipin-1 in Mdr2-KO livers versus control Mdr2+/− livers at the age of 3 months were confirmed at the protein level and showed up-regulation in FVB mice but down-regulation in the B6 strain (Fig. 5A). Mbd1, the gene encoding Mbd1, was significantly down-regulated in the Mdr2-KO/B6 liver, whereas it was significantly up-regulated in the Mdr2-KO/FVB liver (Supporting Table 3).

Intragroup divergence ranged from 0.8 ± 0.5 (%  standard deviation) for subgenotype D6 to 3.0 ± 0.3 for D8. Inter-subgenotype divergence mostly ranged 4–7.5%. Phylogenetic analysis of genotype D showed separation into six distinct clusters (subgenotypes D1,

D2, D3/D6, D4, D5 and D7/D8) with good bootstrap support. The mean intergroup divergence between D3 and D6 was the lowest and fell below the threshold of 4%, which is required to define a subgenotype, suggesting that subgenotypes D3 and D6 belong to one subgenotype. “D8” is a genotype D/E recombinant, which clusters with D7. A number of signature amino acids were found selleck products in all four open reading frames that could differentiate the subgenotypes, which also showed distinct geographical distribution. There are six and not eight subgenotypes of D, D1–D6, which can be differentiated by distinct clustering with high bootstrap support and signature amino acids. Subgenotypes D3 and “D6” should be reclassified as a single subgenotype D3 and it would be more correct to classify “D8” as a genotype D/E recombinant rather than a subgenotype. “
“Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized

by progressive destruction of the interlobular bile ducts that eventually leads to cirrhosis. Due to its hallmark serological signature, the antimitochondrial antibody (AMA) and similarly associated disease-specific T cell response, PBC is often selleck screening library considered a model autoimmune disease. Despite this, immunosuppressive therapies are ineffective for PBC and the only approved medical treatment is the hydrophilic bile acid, ursodeoxycholic acid (UDCA).1 A biochemical response to UDCA with normalization of alkaline phosphatase (ALP) is not achieved in some 30–40% of patients with PBC. Whilst it is established that responders to UDCA have a normal life expectancy, non-responders are at an increased risk of progression to liver transplantation or death.2,3 For this reason, the impetus for the discovery of adjuvant or alternative medical therapies for PBC persists. The potential efficacy of

farnesoid X (FXR) receptor agonists such as obeticholic acid (OCA) are currently being evaluated in international multi centre trials with promising results in this group of refractory PBC patients.4 OCA is the first-in class agonist see more of the nuclear receptor farnesoid X, which controls bile acid synthesis and bile flow in the liver. The potential role of fibrate therapy in PBC first became evident in the early 1990s when patients receiving fibrates for hypercholesterolemia were noted to have a reduction in their serum total ALP. In 1993, Day and colleagues demonstrated that this change resulted from reduced hepatic production of ALP.5 More recently, fibrates have been shown to activate peroxisome proliferator-activated receptor α (PPARα) and upregulate the expression of multiple drug resistance gene-3 (MDR3), both of which potentially ameliorate hepatic inflammation.

“
“Summary.  In this study,

we describe a flow cytometry (FC) system for detecting antibodies to factor VIII (FVIII) and compare its results with those of enzyme-linked immunosorbent assay (ELISA) that detects both inhibitory (I-Ab) and non-inhibitory (NI-Ab) antibodies and the Nijmegen modification of the Bethesda method, detecting I-Ab. FC was set up in our laboratory. Recombinant FVIII (rFVIII) was coupled to microspheres (FVIII-m) and reacted with different plasma dilutions. Microspheres without rFVIII were used as control (control-m). Captured anti-FVIII antibodies were detected using anti-human IgG. Plasma samples buy Small molecule library from the following patients with severe haemophilia A (SHA) patients were evaluated: 17 P (patients without I-Ab, <0.5 BU mL−1); 13 PI (patients with I-Ab, 1.1–8200 BU mL−1). Of these 13, two PI were referred during immune tolerance induction (ITI), and plasmas from 12 healthy donors (HD) were evaluated. Semiquantitative results were given as an index

(the highest mean fluorescence intensity ratio between FVIII-m and control-m multiplied by the inverse of the corresponding plasma dilution). Both plasma and serum were suitable for the test. FC agreed with the Bethesda method (r = 0.8; P = 0.0001). FC and ELISA had 80% of coincidence. Four of 17 patients (23.5%) had NI-Ab by FC, and two of them developed high levels of I-Ab later on. This test provides a useful alternative for measuring FVIII antibodies I-BET-762 supplier supplementing Bethesda assay. FC is fast and easy to perform. No more than 200 μL of plasma or serum is required especially making it useful for paediatric patients. “
“Summary.  Inhibitor development remains a challenge to appropriate haemophilia treatment. This challenge is being addressed, in part, by an expanding knowledge of the

mechanisms that drive inhibitor development including how elements of the innate immune response play a role in inhibitor development. There are promising therapies that may suppress an active immune response. Models to assess the immune responses are becoming ever more sophisticated. Newer models learn more can be used at the preclinical level to evaluate the role of MHC-class II presentation of antigens in both in vitro cell culture studies and in vivo in transgenic mice that express either the protein to be studied or that express human MHC-class II proteins. Parallel to work designed to reduce or reverse inhibitors is development of improved therapies including bypassing agents to treat patients with inhibitors. With these new treatment modalities comes the problem of assessing efficacy at the preclinical level. Models to evaluate bleeding are being developed that may give a more subtle assessment of bypassing agents. These models represent in part an attempt to incorporate the role of ongoing bleeding into the evaluation.

13-16 Two major types of signals have been described to regulate targeting and trafficking of a number of receptor proteins: (1) a tyrosine-based YXXØ sequence in which Ø is an amino acid with a bulky hydrophobic group; and (2) dileucine-based LL motifs in which the latter leucine may be replaced by a hydrophobic amino acid residue.16-19 Depending on the primary sequence context and the selleck chemicals llc relative position of

the motif relative to the membrane, these motifs serve as plasma membrane targeting signals.20, 21 They are also used for efficient sorting to the endosomal system where the protein may be recycled or transported to the lysosome for degradation.22 Adaptin 2 (AP2) is a plasma membrane–localized clathrin adaptor whose subunits bind directly to tyrosine-based YxxØ or NPXY internalization motifs within cytoplasmic or transmembrane regions of proteins to mediate clathrin-dependent endocytosis.23-27 For example, the cytosolic domain of another ABC transporter, cystic fibrosis transmembrane regulator (CFTR) has numerous consensus endocytic motifs that regulate the clathrin-dependent endocytosis.14, 28 However, the presence

of discrete sorting signals in the cytosolic tail of BSEP has not been elucidated. In this study, we tested whether the C-terminus of human BSEP has a targeting/trafficking signal and whether it contributes to the cell surface expression of BSEP. We demonstrated Ku-0059436 manufacturer by domain swapping using the C-terminal region of BSEP attached to Tac (interleukin-2 receptor α [IL-2Rα]) that an internalization motif is present in BSEP. Tac is a cell surface type 1 transmembrane

protein that is targeted to the plasma membrane by default. Tac chimeras have been extensively used for the identification of trafficking signals because of the monomeric nature of the Tac protein and the existence of highly specific N-terminal antibodies to track the chimeric protein.29 We identified by mutagenesis analysis the exact motif in BSEP as a YYKLV sequence. By transferring this YYKLV motif directly to Tac, we further showed that this learn more motif is sufficient for internalization. Finally, we demonstrated that this motif is functional in the full-length human BSEP. ABC, ATP-binding cassette; AP, adaptin; ATP, adenosine triphosphate; ATPase, adenosine triphosphatase; BSA, bovine serum albumin; BSEP/Bsep, bile salt export pump; cAMP, cyclic adenosine monophosphate; CFTR, cystic fibrosis transmembrane regulator; ELISA, enzyme-linked immunosorbent assay; ER, endoplasmic reticulum; GTPase, guanosine triphosphatase; HRP, horseradish peroxidase; IL-2R α, interleukin-2 receptor α; Leu, leucine; MDCK, Madin–Darby canine kidney; MDR1, multidrug resistant 1 P.