0001 in risk allele cases and P < 0.0001 in non-risk allele cases; TNIP3: P = 0.050 in risk allele cases and P = 0.026 in non-risk allele cases). Table 4 shows the average expression level of genes in each SNP genotype. Of the Alisertib cell line 10 genes, IGF2R was the only gene with an expression level that was significantly lower in the non-risk allele cases than in the risk allele cases (P = 0.012). In this study, the expression of IGF2R varied with the genotype of the SNP, rs6983267, at 8q24, which suggested that the carcinogenesis of CRC associated with diabetes mellitus or metabolic syndrome occurs via loss of IGF2R expression in the non-risk allele of 8q24. Additionally,

we analyzed the association between IGF2R downregulation and diabetes mellitus in 8q24 non-risk allele CRC cases by gene set enrichment analysis.12 First, we divided 85 non-risk allele cases into nine cases with diabetes and 76 cases without diabetes. Although positive correlation was not found in any gene set, negative correlation was observed in nine gene sets including IGF2R related to cancer in diabetic cases. Table 5 shows the nine gene sets. In this study, we investigated the association between the SNP at 8q24 and important genes of environmental risk factors of CRC (diabetes mellitus, hyperlipidemia, and metabolic syndrome) using array-CGH and cDNA microarray. IGF2R

was the only molecule associated with CRC in non-risk allele cases with diabetes in this study. Ivacaftor With respect to the mechanism of colorectal carcinogenesis from diabetes or metabolic syndrome, hyperglycemia, hyperinsulinemia, and insulin

resistance are causal factors of CRC.5 Although it is widely known that IGF1R mediates carcinogenesis of various cancers, including CRC, IGF2R, which encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis, has also proven to be associated with cancer. IGF2R is considered a tumor suppressor, and the loss of IGF2R has been described in many human malignancies, including CRC.13 Moreover, MCE IGF2R is located at chromosome 6q26, a region that has been shown to be related to insulin resistance and obesity-related metabolic phenotypes.14 In principle, IGF2R downregulation should be validated, but Western blotting could not be performed because of the difficulty of sample collection. However, our data and gene set enrichment analysis indicated a correlation between the genotype of rs6983267 at 8q24 and IGF2R expression level, which is associated with carcinogenesis and diabetes, not in risk allele but non-risk allele cases with diabetes mellitus. This result suggests that the SNP at 8q24 makes diabetes a risk factor for colorectal carcinogenesis via IGF2R especially in non-risk allele cases, even though the way the SNP at 8q24 works on diabetes or the relation of IGF2R to CRC carcinogenesis is not clear.

Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future. “
“MicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV)

infection. Herein, we demonstrate see more that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models. Overexpression of the HCV proteins core and NS4B independently activates miR-27 expression. Furthermore, we establish that miR-27 overexpression in hepatocytes results in larger and more abundant lipid droplets, as observed by coherent anti-Stokes Raman scattering (CARS) microscopy. This hepatic lipid droplet accumulation coincides with miR-27b’s repression of peroxisome proliferator-activated receptor (PPAR)-α and angiopoietin-like protein 3 (ANGPTL3), known regulators of triglyceride homeostasis. We further demonstrate

that treatment with a PPAR-α agonist, bezafibrate, is able to reverse the miR-27b-induced lipid accumulation in Huh7 cells. This miR-27b-mediated repression of PPAR-α signaling represents a novel mechanism of HCV-induced hepatic steatosis. This link was further demonstrated in vivo through the correlation between miR-27b expression levels and hepatic lipid accumulation in HCV-infected SCID-beige/Alb-uPa mice. Conclusion: Collectively, our results highlight HCV’s up-regulation of miR-27 expression as a novel mechanism contributing to the development MCE公司 of hepatic steatosis. (Hepatology 2014;58:98–108) Sotrastaurin mw Hepatitis C virus (HCV) is a positive sense RNA virus from the Flaviviridae family[1] that currently infects ∼2.35% of the global population.[2] HCV encodes three structural proteins (core, E1, and E2) and seven nonstructural proteins (p7,

NS2, NS3, NS4A, NS4B, NS5A, and NS5B), and relies on host pathways to facilitate its lifecycle.[3] HCV-associated host factors include both coding and noncoding genes, such as microRNAs (miRNAs), which are small RNAs, ∼20-25 nucleotides in length, which posttranscriptionally regulate virtually every cellular pathway.[4] Unlike synthetic silencing RNAs that are designed to target individual genes, miRNAs have evolved to regulate many targets, thereby exerting greater regulatory control. Several viruses modulate the host miRNAs for their pathogenesis.[5] HCV displays interactions with components of the RNA silencing pathway,[6-8] and direct interactions with a liver-abundant miRNA, miR-122.[5, 9] Hepatic miRNAs can influence HCV either through direct interactions with the viral genome or regulation of HCV-associated host pathways.[6] MicroRNA-27 (miR-27) represents a liver-abundant miRNA[10] whose role in HCV pathogenesis is poorly understood. miR-27 regulates lipid metabolism in adipocytes and macrophages and is implicated in atherosclerosis.

24 In addition, social factors, such as income, education, employment, and access to health care, may contribute to disparities in survival. For example, a U.S. study of area-level median household income found better survival among treated HCC patients from high- versus low-income counties.19 In this study, the proportion of HCC diagnoses that were histologically confirmed decreased with time. Possible reasons could include changes in etiology or comorbidities of HCC cases.24 Histologic confirmation is also likely to be affected by guidelines 5-Fluoracil price affirming the use of noninvasive diagnostic5 and clinical management procedures under specified circumstances.5,

8 This study had strengths, including availability of trend data for stage and treatment as well as HCC survival data with sufficient counts to estimate survival within race and treatment subgroups. Caution is, however, recommended when interpreting the findings because of limited information on the method of diagnosis, as well as patient comorbidities, HCC etiology, and treatment. Though the favorable survival associated with curative therapy selleck in this report is thought to be meaningful, lead-time bias resulting from earlier diagnosis should not be dismissed as a contributory factor.25 Furthermore, the SEER-13

registries include only 14% of the U.S. population, with racial and economic attributes that differ in several meaningful ways from those of the entire nation. For example, large Asian or Pacific 上海皓元医药股份有限公司 Islander populations are found in the Hawaii, Seattle, and California registries of SEER-13, whereas Hispanic populations in Florida and Texas are not. The SEER-13 population is more urban than the United States. Although SEER-13 contains 14% of the nation’s population, it contains 22% of U.S. liver transplant centers.26 Despite these limitations, the

findings suggest that HCC diagnosis and management are changing in the SEER-13 population, with favorable results on stage, treatment, and survival. In summary, the detection of early stage HCC among at-risk persons may enable the use of potentially curative therapies. This is likely to contribute to the improving survival described in this report. The small percentage of cases receiving either liver surgery or ablation therapy (22%) suggests that the potential exists for further improvement in survival, with ongoing implementation of the HCC control efforts already improving the prognoses of HCC cases. We thank Carol Johnson, Leon Sun, Kathleen Cronin, Carol Kosary, Lynn Ries, Jennifer Ruhl, Susan Devesa, Nadia Howlader (critical review), Neil Neyman (coding), the U.S. Census Bureau (population data), SEER registries (population-based surveillance) and IMS, Inc. (data file).

The ethnic Malays of northeastern Peninsular Malaysia RAD001 nmr have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence.

Contrary to predictions, in Malays, erosive esophagitis, Barrett’s esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori-infected non-Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection

in see more Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane. “
“In developing countries, more than 50% of children have serological evidence of Helicobacter pylori infection. However, serological tests for H. pylori did not differentiate between active and past infection.

The objectives of this study were to estimate the frequency of active and past H. pylori infection utilizing functional urea breath test (UBT) and serological tests and evaluate factors associated with the infection. A total of 675 school children, 6–13 years of age, participated. UBT was performed to detect active H. pylori infection. Blood samples were obtained to determine iron status and Immunoglobulin G (IgG) responses to the H. pylori whole-cell and to Cag A antigens by antigen-specific enzyme-linked immunosorbent assays. 上海皓元 Weight, height, and sociodemographic characteristics were recorded. A total of 37.9% (95% Confidence Intervals (CI): 34.2–41.6) of school children had active or past H. pylori infection; of them, 73.8% (CI95% 68.4−79.2) were carrying CagA-positive strain, 26.5% (CI95% 23.2–29.8) had active infection, and 11.4% (95%CI: 9.0–13.8) had evidence of past H. pylori infection. School children with iron deficiency and low height for age had higher risk of H. pylori infection: [OR to active or past infection was 2.30 (CI 95% 1.01–5.23) and to active infection it was 2.64 (CI 95% 1.09–6.44)] compared to school children with normal iron status and height for age or with normal iron status but low height for age or with iron deficiency and normal height for age. The estimated prevalence of infection depends of the test utilized. Frequency of H.

Suppression of the PI3K–AKT–HIF-1α pathway

interfered with p28GANK-mediated EMT and invasion. Consistently, we detected a significant correlation between p28GANK expression and p-AKT levels in a cohort of HCC biopsies, and the combination of these two parameters is a more powerful predictor of poor prognosis. Conclusion: These results present novel mechanistic insight into a critical role of p28GANK in HCC progression and metastasis. (HEPATOLOGY 2011) Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, and the second in China.1, 2 HCCs that grow rapidly with early vascular invasion are highly resistant to chemotherapy.3-5 The extremely poor prognosis of patients with HCC is largely due to the high frequency of tumor recurrence or distant metastasis after GSK1120212 chemical structure surgical resection.6 Extensive epidemiological studies have identified major risk factors of HCC, and significant advances have

been made in understanding the pathogenesis.7 However, little is known about molecular mechanisms underlying recurrence or metastasis. Therefore, a most critical issue is to search for molecular markers FK228 nmr related to metastasis, which will provide new targets for intervention of metastatic recurrence of HCC. p28GANK (also known as gankyrin, PSMD10, or p28) was identified as an oncoprotein that is frequently overexpressed in human liver cancers.8, 9 Up-regulation of p28GANK MCE公司 correlates well with cell cycle progression in human hepatocytes.10, 11 Gankyrin overexpression confers tumorigenicity to NIH3T3 cells and inhibits apoptosis in cultured human tumor cells exposed to chemotherapeutic agents.8, 12 The tumorigenic effect of p28GANK might be associated with its antiapoptotic property,11–14 and down-regulation of p28GANK-induced apoptosis inhibits tumor growth.11, 12, 14 The antiapoptotic activity is attributable, at least in part, to increased degradation of p53, resulting in reduced expression of p53-dependent proapoptotic genes.12

Additionally, p28GANK was shown to bind v-rel reticuloendotheliosis viral oncogene homolog A (RelA)/nuclear factor κB (NF-κB) and suppress NF-κB activity.15, 16 Therefore, p28GANK may play a complex role in hepatocarcinogenesis, which is yet to be elucidated. In this study, we extensively investigated p28GANK expression pattern and determined its contribution to HCC invasion and metastasis. We also dissected the molecular mechanisms by which p28GANK mediates tumor metastasis. Results presented here suggest that p28GANK overexpression promotes HCC aggression via modulation of phosphoinositide 3-kinase (PI3K)–v-akt murine thymoma viral oncogene homolog 1 (AKT)–hypoxia-inducible factor-1α (HIF-1α) signaling.

Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient’s human lysosomal acid lipase activity was 0.020 nM/min per 106 cells, corresponding to 5.9% of that

MK0683 clinical trial in healthy subjects (0.332 ± 0.066 nM/min per 106 cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported. “
“Bile acid synthesis not only produces physiological detergents required for intestinal nutrient absorption, but also plays a critical role in regulating hepatic and whole-body metabolic homeostasis. We recently reported that overexpression of cholesterol 7α-hydroxylase (CYP7A1) Selleckchem Anti-infection Compound Library in the liver resulted in improved metabolic homeostasis in Cyp7a1 transgenic (Cyp7a1-tg) mice. This study further investigated the molecular links between bile acid metabolism and lipid homeostasis. Microarray gene profiling revealed that CYP7A1 overexpression

led to marked activation of the steroid response element-binding protein 2 (SREBP2)-regulated cholesterol metabolic network and absence of bile acid repression of lipogenic gene expression in livers of Cyp7a1-tg mice. Interestingly, Cyp7a1-tg mice showed significantly elevated

hepatic cholesterol synthesis rates, but reduced hepatic fatty acid synthesis rates, which was accompanied by increased 14C-glucose-derived acetyl-coenzyme A incorporation into sterols for fecal excretion. Induction of SREBP2 also coinduces intronic microRNA-33a (miR-33a) in the SREBP2 gene in Cyp7a1-tg mice. Overexpression of miR-33a in the liver resulted in decreased bile acid pool, increased hepatic cholesterol content, and lowered serum cholesterol in mice. Conclusion: This study suggests that a CYP7A1/SREBP2/miR-33a axis plays a critical role in regulation of hepatic cholesterol, MCE公司 bile acid, and fatty acid synthesis. Antagonism of miR-33a may be a potential strategy to increase bile acid synthesis to maintain lipid homeostasis and prevent nonalcoholic fatty liver disease, diabetes, and obesity. (Hepatology 2013;53:1111–1121) Bile acids are synthesized from cholesterol exclusively in the liver.[1] The rate of bile acid synthesis is mainly controlled by transcriptional regulation of cholesterol 7α-hydroxylase (CYP7A1),[1] which encodes the rate-limiting enzyme in the classic bile acid synthesis pathway. When bile acid levels increase, bile acids repress their own synthesis and stimulate biliary lipid secretion.

Furthermore, miR-19a/b decreased PTEN but increased AKT phosphorylation in gastric cancer cells. Conclusion: miR-19a/b find more promote MDR of gastric cancer cells by targeting PTEN, leading to drug efflux acceleration and drug induced apoptosis suppression. This novel miR-19a/b-PTEN-AKT axis sheds new light on the mechanisms underlying MDR and may provide future therapeutic targets for the treatment of gastric cancer. Key Word(s): 1. microRNA-19a/b; 2. gastric cancer; 3. multidrug resistance; 4. PTEN; Presenting Author: LI WANG Additional Authors: LIYA ZHOU, YUAN LI, ZHU JIN, YAJING HAN Corresponding

Author: LIYA ZHOU Affiliations: peking university third hospital Objective: Gastrin and its target cell constitute an important neuroendocrine axis of the stomach and it physiologically has trophic effect on the mucous cell. Nowadays these neuroendocrine factors are considered correlated with the development of gastric carcinoma. Our research aimed to explicit the different levels of neuroendocrine markers between gastric cancer and other gastric diseases, and to explore the potential contribution of these factors in the development of gastric cancer Methods: 56 consecutive operation samples of gastric cancer patients from General Selleck PD0325901 Surgery in our hospital were

obtained, and endoscopic specimen of 80 including gastritis, intestinal metaplasia, atypical hyperplasia and gastric cancer patients as well, 20 cases in each subgroup. The levels of gastrin, chromograninA (CgA), histidine decarboxylase (HDC) and cholecystokinin-2 receptor (CCK2R) were detected by immunohistochemical analysis. Analyzing the staining results of gastrin with IPP (Image pro plus) software. SPSS 16.0 for statistic calculation Results: Gastrin and HDC levels were higher MCE公司 in antrum (P=0.000 and 0.033, respectively) but CCK2R level was higher in corpus (P=0.013). During the steps of gastritis, intestinal metaplasia, atypical hyperplasia and cancer, there was a fluctuation of these markers and the tendency of gastrin,

CgA, HDC were decrease-increase-decrease, but for CCK2R it was increase-decrease-decrease, and the tendency was only located at antrum but not corpus. Gastrin, CgA and HDC levels were all higher in signet-ring cell carcinoma group than glandular carcinoma group (P=0.005, 0.000 and 0.001 respectively). Finally, the sources of these differences were enterochromaffin like cell instead of other neuroendocrine cells (P=0.000) Conclusion: Neuroendocrine factors present a series of changes in the steps of cancer, which indicated that these factors had a certain relationship with gastric cancer development. What’s more, the higher levels in signet-ring cell carcinoma showed a closer involvement in this pathologic type, and the mechanism still needs further investigation Key Word(s): 1. gastric cancer; 2. gastrin; 3. ECL cell; 4.

8 In addition to the ability of HCV to trigger the TLR3 pathway,9, 10 the increased number of Th17 cells appears to be associated with the severity of liver inflammation in chronic HCV patients and treatment of infected patients with pegylated selleck chemicals llc interferon (IFN)-α and ribavirin reduced the level of Th17-related cytokines.11 As one of the crucial factors for Th17 differentiation, thymic stromal lymphopoietin (TSLP), a member of the common γ-chain cytokine, is capable of activating (conditioning) DCs, thereby stimulating naïve T cells to differentiate into Th2 cells.12 In addition, DCs treated with both TSLP and poly (I:C) activate naïve T cells and

differentiate into Th2 and Th17 cells.8, 13 Thus, TSLP-activated DCs, which are known to be strong inducers of Th2 responses, can simultaneously induce Th17 cells under certain pathological conditions. In this report CHIR-99021 concentration we demonstrate that the infection of hepatic cells in vitro by HCV triggers robust TSLP production and this HCV-induced production of TSLP is regulated in an nuclear factor kappa B (NFκB)-dependent manner. TSLP secreted by HCV-infected cells activates and conditions human

monocyte-derived DCs to enhance the production of Th17 differentiating cytokines, TGF-β, IL-6, and IL-21 by the DCs. Moreover, the addition of TSLP neutralizing antibody to the coculture of monocytes/DCs with HCV-infected hepatocytes blocks the production of these cytokines. Consistent with these data, we find that the hepatocyte-derived TSLP is readily detected in liver biopsies from chronic HCV patients. Our studies suggest a novel role for the hepatocyte-derived TSLP in the generation of CD4+ Th17 effector T cells through its ability to condition DCs to drive CD4+ Th17 differentiation. The potential implications of these findings in the development of HCV-induced chronic progressive liver disease are discussed. DC, dendritic

cell; HCV, hepatitis C virus; TSLP, thymic stromal lymphopoietin. Human MCE公司 hepatoma cell lines, Huh 7.5.1, were maintained in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 μg/mL). THP-1 cells purchased from the American Tissue Culture Collection (ATCC) were cultured in RPMI 1640 and supplements as recommended by ATCC. Liver biopsies and peripheral blood samples from chronic HCV or control patients were obtained from Dr. Hugo Rosen (University of Colorado). Blood samples were also obtained from the Virginia Blood Services. All information of age, gender, and HCV genotype were previously described.14, 15 For infection of cells with secreted HCV, Huh 7.5.1 permissive cells were seeded at 3 × 106 cells in a T75 plate for 24 hours. Cells were infected with 4 × 104 FFU (multiplicity of infection [MOI] of 0.01) of JFH-1 producing cell supernatant and cultured for 10 days in DMEM-10% FCS media.

If we need to study every problem as if it were a new issue from first principles, then we will always be behind the curve and never be much use at giving advice to managers, sociologists, economists, planners and politicians. As zoologists,

our work is highly relevant to societal needs. The Journal of Zoology is encouraging more interdisciplinary dialogue in order to provide those responsible for developing conservation, management and population recovery plans with access to the specialized knowledge that only zoologists possess about their study animals. Today, papers that focus on a single species and do not elucidate general trends are likely to be sent to a taxon-specific journal. Papers that are primarily about conserving a particular population or managing a specific problem are more likely to be sent to specialized conservation or management journals. This traditional separation of disciplines muddies the interface between zoology and conservation CCI-779 chemical structure selleck and prevents us from exploring the wider implications of basic zoological research. An integrative approach to zoological studies that tell us how we think things generally work for a variety of species – from otters to seals to blue whales

– will improve our ability to face new situations in which relatively little basic information is available. This interim advice, along with an honest appraisal of the resulting uncertainty in our predictions, will allow us to proactively design conservation and management measures that make some scientific sense. Indeed, this is exactly what the Journal aims to address by promoting the synthesis of specialized disciplines and welcoming papers that encompass a wide range of topics and that are truly integrative. “
“Animals must balance their energy budgets even when confronted with

periodic food shortages and/or adverse environmental conditions. Especially, small endothermic animals require large amounts of energy to maintain high and stable body temperatures (Tb) via endogenous heat production. To deal with energetic challenges, many small endotherms are heterothermic, abandon regulation of high Tb and enter a state of torpor resulting in large energy savings. Torpor is used by many bat species because they are small, have high rates of heat loss and 上海皓元 rely on fluctuating food resources (e.g. insects, fruit, nectar). Many bats use torpor all year, but the expression of temporal heterothermy can be strongly seasonal especially for temperate and subtropical species, which may hibernate for long periods. Recent advances in our understanding of torpor expression in bats have been made using temperature telemetry for remote data collection of Tb in free-ranging wild individuals from all climate zones. This new knowledge on free-ranging bats has revealed the importance of torpor expression not only for energy conservation but also for other benefits, such as reduction of extrinsic mortality (e.g. predation).

For now, check details these data conclusively show that parent and clonal EpCAM+CD49f+ cells can organize into organotypic structures that mimic the morphology, ultrastructure, and function of the native gallbladder, both invitro and invivo. Spence et al.7 have recently showed that IHBD cells and EHBD cells develop from separate precursors. However, there are no reports describing their similarities or differences in the adult. We found that expression of CD49f, CD49e, CD81, CD26, CD54, and CD166 was different between primary IHBD cells and gallbladder cells. The aim of our experiment was to evaluate the differences,

if any, between gallbladder stem cells and IHBD cells. Expanded EpCAM+CD49f+ gallbladder cells (>p0) represent a purer stem cell population than primary EpCAM+CD49fhi cells. The latter forms both flat and glandular colonies, and only a fraction of the flat see more colonies can self-renew. Therefore, we ran microarray analyses on expanded EpCAM+CD49f+ cells (>p1) and expanded IHBD cells. The major groups of differentially expressed genes were CYP genes, GST, and the solute carrier family genes. Also, interferon (IFN)-inducible protein 27 was differentially expressed between gallbladder cells and IHBD cells. Interestingly, the expression of CD54 is known to be

immunologically mediated.36 The immunologic properties of bile duct cells have long been considered. They are MCE the primary site of damage in inflammatory diseases, such as primary biliary cirrhosis37 and biliary atresia9 and in liver allograft rejection.38 The differential expression of an IFN-inducible protein and CD54 indicates that the immunologic properties of IHBD cells and gallbladder cells could be different. Studies of IHBD cells are hindered by a technical inability to isolate and expand them from primary tissue.2, 39 We circumvented this hurdle by using LA7 feeder cells that allow for a robust expansion of IHBD epithelial (EpCAM+) cells.

This expansion assay, along with the 3D Matrigel assay, could serve as interchangeable, technically easy tools to study bile duct cells. In all, the complete elucidation of the differences between IHBD cells and gallbladder cells belongs to another study, as does the evaluation of the stem cell characteristics of expanded IHBD cells. The focus of this article was to isolate and characterize gallbladder stem cells. We postulate that this study will have important clinical significance. Gallbladder stem cells could be used to treat biliary atresia, as has been noted with hepatic progenitor cells.40 These cells could also be reprogrammed into hepatocytes or endocrine cells. There have been recent reports of the differentiation of gallbladder epithelial cells into hepatocytes,34, 41 and ectopic endocrine cells have been observed in the EHBD cells of Hes1−/− deficient mice.