Most studies concerning the relationships between lifestyle or dietary factors and FD are based on symptom intensities evaluated by questionnaire or on physiological studies involving particular foods or components. Further prospective studies are necessary to clarify the details of these pathogenetic factors and the role of dietary therapy in the management of FD. Statement 22. An integrated approach

addressing physiological, biological, psychological and social factors is recommended for all patients with functional dyspepsia. (SeeFig. 2) Grade of evidence: low. Strength of recommendation: probably do it. Level of SAHA HDAC agreement: a: 84.2%; b: 10.5%; c: 5.3%; d: 0%; e: 0%; f: 0%. As the pathogenesis of FD is multi-factorial, treatment should be individualized, with an effort to identify as many possible putative factors as possible. There have been no direct data to support this approach to managing FD in general. On the other hand, there have been studies on IBS that demonstrate a favorable response to treatment when physicians make an effort to address possible contributing factors such as past GI infection (biological), psychosocial stressors (psychological) and dietary changes (social), to reassure the patient by providing reasonable evidence that he or she does not have a life-threatening condition, and to explain the diagnosis with appropriate

pathophysiological (physiological) models. In view of the overlap in symptoms, patient demographics and putative pathophysiology, it is reasonable to recommend a similar approach to FD, as was recommended in the recent Selleck LY2606368 Asian IBS Consensus.137–139 There is a study to support adopting a combination of intensive medical therapy with psychological intervention in patients with refractory FD. Haag et al.,140 in a prospective randomized, controlled trial, compared the long-term outcome of intensive medical therapy (with or without cognitive-behavioral or muscle relaxation therapy) versus standard medical therapy in patients with refractory FD and found that in FD patients with refractory symptoms, intensified medical management involving function testing and psychological

intervention yielded superior long-term outcomes. There is also a study from China that showed psychological intervention to be superior to prokinetic therapy.141 very Statement 23. Where socio-economic conditions allow, Helicobacter pylori testing and eradication should be part of the management strategy for all patients in Asia who present with dyspepsia. (SeeFig. 2) Grade of evidence: high. Strength of recommendation: do it. Level of agreement: a: 58.0%; b: 42.0%; c: 0%; d: 0%; e: 0%; f: 0%. Helicobacter pylori eradication has a statistically significant effect on symptom relief in patients with FD. Cochrane meta-analysis on 17 randomized controlled trials (n = 3566) found a small but statistically significant benefit of H.

14,100,101 In an extensive and influential review (see Table 2), it was suggested that neural activation releases vasoactive neurotransmitters from their afferent processes, which in turn provokes inflammatory changes in peripheral target tissues (in this instance, cerebral blood vessels).14 In addition, the data suggested that the release of substance

P (a vasodilator) from sensory fibers is important in mediating changes in vessel permeability. The finding in animals explains the unilateral distribution of migraine pain and could challenge the concept that the pain of vascular headache is due to dilating blood vessels. Finally, it Nutlin3a was suggested that there is a sterile inflammation of cranial blood vessels during migraine JNK inhibitor order attacks. Moskowitz concluded that “the relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.”14 Studies along this line were carried out in the subsequent year and in 1987 a model of intracranial neurogenic inflammation was presented for use in rat.102 Electrical stimulation of the trigeminal ganglion resulted in ipsilateral

increase of tracers in the dura. In contrast, there was no extravasation in the brain.102 The neurogenic inflammation model was then used to demonstrate that ergot alkaloids, ergotamine, and dihydroergotamine, inhibited plasma extravasation and it was suggested “that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura.103 Similar results

were obtained for indomethacin and aspirin104 and sumatriptan.105 It was suggested that the effect was mediated by 5-HT1B/1D receptors located on sensory trigeminal neurons.106,107 Up to now all effective, acute antimigraine drugs have indeed been proven to inhibit neurogenic protein extravasation (NPE).105,107,108 Bupivacaine However, inhibition of NPE was not predictive for the antimigraine effect of all investigated new drug-groups. Thus, in 5 placebo-controlled clinical studies, drugs (eg, endothelin and NK-1 receptor antagonists) with potent inhibitory effect on dural NPE were not effective for acute migraine treatment.109-113 Because specific NPE inhibitors are without an effect in migraine, it has been difficult to find a pivotal role for dural neurogenic inflammation in migraine. It was shown, however, that valproate, which is effective in migraine prophylaxis, blocked plasma extravasion in the meninges.

CXCR2-targeted mutant mice

were generated by the mating of heterozygote C.129S2(B6)-Il8rbtm1Mwm/J (Il8rbtm1Mwm/Il8rb+) mice (Jackson Laboratory, Bar Harbor, MN) in the University of Michigan animal facility. CXCR2 mutant (Il8rbtm1Mwm/Il8rbtm1Mwm) mice and CXCR2 wild-type (Il8rb+/Il8rb+) Belnacasan mice were used in all experiments; wild-type and mutant mice were based on the mouse 129 strain. All experiments were performed in compliance with the standards for animal use and care set by the University of Michigan’s committee on the use and care of animals. Animals were fasted overnight, and APAP or an equal volume of phosphate-buffered saline (PBS) was administered intraperitoneally.9 For mortality experiments, animals received 750 or 1000 mg/kg APAP; for all other experiments, 375 mg/kg was used. On the basis of previous experiments with this strain of mouse, 750 mg/kg APAP is approximately the median lethal dose, and 375 mg/kg

is approximately the 25% lethal dose. To confirm that apoptosis is important in the APAP-induced liver injury in this model, additional experiments were performed with the pancaspase inhibitor Q-VD-OPh. Q-VD-OPh is more effective at preventing GSK2118436 mouse apoptosis than other inhibitors, such as ZVAD-fmk and Boc-D-fmk, and is nontoxic to cells, even at high doses.10 This compound prevents apoptosis mediated by the three major apoptotic pathways: RG7420 price caspase-9/3, caspase-8/10, and caspase-12.10 Q-VD-OPh (50 mg/kg; R&D Systems, Minneapolis, MN) was administered

1 hour before APAP injection; control animals received an equivalent dose of vehicle. Animals were then sacrificed according to protocol, and apoptosis was measured by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and DNA fragmentation assay. Serum AST and ALT were measured in CXCR2 knockout and wild-type mice 24, 48, and 72 hours after APAP or PBS administration. Animals were sacrificed, their blood was collected, and the serum was separated from the clotted blood by centrifugation at 4000 rpm for 15 minutes at 4°C. ALT and AST were measured with a Diagnostics ALT and AST test kit from Sigma Chemical Co. (St. Louis, MO). Mouse livers were perfused with a perfusion medium (Gibco, Grand Island, NY) to remove intravascular blood.

As shown in Supporting Fig. 9, the mRNA levels of GPx2, GCLC, and GCLM were increased in cells treated with tBHQ. Furthermore, we investigate whether AIB1 is involved in the transactivation of Nrf2. Overexpression of AIB1 enhanced Nrf2-mediated ARE reporter activity (Fig. 6B, left panel), whereas knockdown of AIB1 significantly

reduced Nrf2-mediated ARE reporter activity (Fig. 6B, right panel). In addition, overexpression of AIB1 also significantly increased Nrf2-mediated GPx2-promoter activity (Supporting Fig. 10). To further confirm that AIB1 regulates these genes through the Nrf2 pathway, knockdown of Nrf2 was performed in QBC939 cells. As expected, knockdown of Nrf2 reduced the expression of GPx2, GCLC, and GCLM (Fig. 6C). Nrf2 knockdown resulted in increased ROS levels in cells and

increased sensitivity of cells to cisplatin-induced apoptosis (Fig. 6B,C). In addition, Nrf2 knockdown reduced cell proliferation C59 wnt and resulted in G2/M arrest (Supporting Fig. 11). These phenotypic changes highly resembled that in AIB1-knockdown cells. Collectively, these results indicate that AIB1 is an essential coactivator of Nrf2 and the effects of AIB1 on CCA cell proliferation and chemoresistance are at Fluorouracil ic50 least in part mediated through the Nrf2 pathway. In addition to up-regulation of antiapoptotic genes to evade apoptosis, up-regulation of drug transporters to accelerate drug efflux is commonly used by cancer cells to resist chemotherapeutic drugs. ATP-binding cassette transporters such as ABCC2 and ABCG2, two targets of Nrf2, have been implicated in the multidrug resistance of cancer cells through enhancing drug efflux.14 Knockdown of Nrf2 reduced the expression of ABCC2 and ABCG2 (Fig. 7A), confirming that the expression of ABCC2 and ABCG2 is regulated by Nrf2. Consistent with the notion that AIB1 is an essential coactivator for Nrf2 activation, Rebamipide AIB1 knockdown reduced the expression of ABCC2 and ABCG2, but not ABCC1 and ABCC3 (Fig. 7B), and overexpression of AIB1 significantly increased Nrf2-mediated

ABCC2-promoter activity (Fig. 7C). Furthermore, the effects of AIB1 in drug efflux were determined by measuring intracellular content of the autofluorescent drug mitoxantrone (MTX) in CCA cells. AIB1 knockdown significantly increased drug accumulation in QBC939 cells (Fig. 7D), whereas overexpression of AIB1 significantly decreased drug accumulation in HCCC9810 cells (Fig. 7E). These results suggest that AIB1 promotes drug efflux by increasing the expression of ABCC2 and ABCG2. To determine whether AIB1 physically interacts with Nrf2 to conduct its coactivating function, Flag-tagged AIB1 and HA-tagged Nrf2 were coexpressed in 293T cells, then Co-IP assays were performed. As shown in upper panel of Fig. 8A, anti-Flag antibodies, but not control IgG, immunoprecipitated Nrf2 from cell lysates. Reciprocally, anti-HA antibodies could also immunoprecipitate AIB1 from cell lysates (Fig. 8A, lower panel).

279, n = 13, NS) and SPL (rS = −0.022, n = 13, NS) were not significantly correlated to seahorse height. Moreover, no differences were found between males and females in these sound characteristics (t-test; P > 0.05 in all cases; see Table 1). These comprised short single pulses with mean duration

of 19.4 ms (Table 1; Fig. 1b), main energy between 100 Lumacaftor price and 800 Hz and SPL (re: 2 cm) of 105.0 dB. The SPLs of courtship clicks were lower than of feeding clicks but did not differ from distress growls (see next topic) (Kruskal–Wallis test: H = 12.9; n = 20, P < 0.01; Dunn's post hoc: P < 0.001). Male courtship clicks had higher SPLs than clicks of females [t-test: t = 5.10, degrees of freedom (d.f.) = 11, P < 0.01; Table 1], but with similar duration and dominant frequency (t-tests, P > 0.05 in both cases; Table 1). Sex differences in SPL were not due to differences in size as the sound characteristics of courtship clicks were not correlated to body height (SPL: r = 0.490; duration: r = 0.276; dominant frequency: r = 0.468; in all cases, n = 10, P > 0.05). Hippocampus reidi’s courtship lasted for 3 days and encompassed a sequence of behaviours accompanied by sound production (Table 2). The behaviour pouch pumping was the most frequently associated with clicks (63.6%), followed by

promenading (25.0%), brightening (9.1%) and raising (2.3%), whereas no sounds were emitted during circling, quivering, NVP-LDE225 in vitro pointing, attempting to copulate and copulating. Both males and females produced click sounds during courtship, and sound production mostly (86.1%) took place when the distances between the fishes were <15 cm. The number

of sounds produced by males and females during courtship did not differ significantly from one another, neither considering all days together (U-test: U = 6.0, n = 10, NS) nor separately (U-tests, n = 10 in all cases: day 1, U = 10.0, NS; day 2, U = 9.5, NS; day 3, U = 7.0, NS). A considerable O-methylated flavonoid increase in click production was observed on the last (third) day of courtship (Friedman test: χ2 = 15.2, d.f. = 2, P < 0.001, Dunn’s post hoc: P < 0.05; Fig. 2). When considering sexes separately, differences in click production among courtship days were detected for both females (Friedman test: χ2 = 7.176, d.f. = 2, P < 0.05, Dunn’s post hoc: NS) and males (Friedman test: χ2 = 8.588, d.f. = 2, P < 0.05, Dunn’s post hoc: P < 0.05), both of which produced more clicks on the last day in comparison with the first day. Seahorses emitted low-frequency growling sounds while handheld. Growls consisted of series of sound pulses often lasting as long as the fish were handheld (maximum duration: 260 s) (Fig. 1c). The mean duration of sound pulses was 35.6 ms, with a mean pulse period of 111.2 ms. The mean SPL was 115.0 dB and the main energy was concentrated below 200 Hz (see Table 1). During production of growling sounds the seahorse’s body vibrated. Growls could not be recorded during feeding or courtship.

Our data on 103 field-collected toads (53 of which contained lungworms) support this prediction. Exercise induced a greater increase in heartbeat rate in infected toads than in uninfected conspecifics, but no shift in oxygen saturation of the haemoglobin. “
“Rostral appendages occur in a very small number of species spread across the entire clade of iguanian lizards. The five species of Sri Lankan agamid lizards of the poorly known endemic genus Ceratophora show

remarkable variation in the morphology and development of rostral appendages, which are absent in two species and present in the other three. Parsimony and Bayesian comparative methods do not robustly resolve whether the appendage evolved once (with two losses), twice (with one loss) or thrice independently. The appendage in C. tennentii is leaf-shaped, present in juveniles and monomorphic in adults. It is Roxadustat Fulvestrant mouse quite dissimilar to the appendages in C. aspera and C. stoddartii which are horn-shaped, absent in juveniles and dimorphic in adults. Ceratophora stoddartii is more closely related to C. erdeleni, which

lacks the rostral appendage, than it is to C. aspera. The combined morphological, allometric and phylogenetic evidence suggests rostral appendages evolved three times within Ceratophora: perhaps once as a result of natural selection for crypsis (in C. tennentii) and twice as a result of sexual selection (in C. aspera and C. stoddartii). Our results suggest that these unusual ornaments can evolve by more than

one mechanism and more readily than is suggested by their low frequency among iguanian lizards. “
“Activity and behavior patterns are important Y-27632 2HCl components of a given species’ ecological strategy, as they have profound implications for its survival and reproduction. Here, we studied the activities, movements and secretive behavior of the thin-spined porcupine Chaetomys subspinosus (Rodentia: Erethizontidae), a threatened arboreal folivore in the Brazilian Atlantic rainforest. We aimed to ascertain the behavioral strategies used by this species as well as its responses to seasonal and daily climatic changes. Four radio-collared individuals were followed continuously for 72-h in the summer and winter, as well as during 146 half-night sessions conducted from April 2005 to September 2006 in forest remnants in southern Bahia. The thin-spined porcupines were nocturnally active (17:30–05:40 h), with peaks in activity and movement from 19:00 to 20:00 h and 03:00 to 04:00 h. Animals followed a circadian rhythm of activity during both the summer and winter. During the diel cycle, porcupines spent 74% of their time resting, 14% feeding, 11% traveling and 2% performing other activities. Distance traveled during the diel cycle averaged 277.5 ± 117.9 m sd. The mean movement rate during the night was 21.6 ± 30.1 m/h sd.

2A,B, respectively. The TCR-L/IFNα fusion proteins were expressed transiently in HEK293 human embryonic kidney cells and purified by two chromatographic steps to greater than 95% purity and an aggregate content below 1%. Purity, absence of aggregates, and correct composition of the tetrameric cTCR-L/IFNα were analyzed by reducing and nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Fig. 2C,D) and analytical size-exclusion chromatography (data not shown). The migration of the antibodies under nonreducing

conditions in SDS-PAGE was consistent with the molecular masses expected from the assembly of the four protein chains that together form the TCR-L/IFNα fusion protein (Fig. 2C). The molecular masses of the cTCR-L/IFNα and sTCR-L/IFNα as predicted

from the amino acid sequences are 184998 Da and 184242 Da, respectively. SDS-PAGE analysis of DNA Damage inhibitor the TCR-L/IFNα under reducing conditions further revealed a band for the TCR-L/IFNα heavy chain with an apparent molecular mass of ≈74 kDa in comparison to the parental antibody heavy chain with an apparent molecular mass of ≈55 kDa, reflecting the increased mass from IFNα addition and expected glycosylation heterogeneity caused by N-linked antibody Fc-glycosylation and potential O-linked glycosylation of the IFNα moiety. The identity and integrity of the protein sequences of the antibody fusion proteins were verified by mass spectrometry after removal

of N- and O-glycans https://www.selleckchem.com/products/gdc-0068.html by enzymatic treatment with peptide-N-glycosidase (50 mU), neuraminidase (50 mU), and O-glycosidase (2.5 mU) as described for HEK293-derived CrossMab antibodies15 (data not shown). Fusion of IFNα to large molecules, like polyethylene glycol (Peg) or albumin, increases its plasma half-life dramatically16-18 but the effect of such modifications on the IFNα biological activity remains difficult to predict. Different Peg-IFNα or albumin/IFNα conjugates showed 1%-30% of the biological activity of the native IFNα,18, 19 whereas IL-2 fused to an antitumor antibody retained its full biological activity.20 The biological in vitro activity of our two TCR-L/IFNα fusion proteins in comparison Adenosine to native unconjugated IFNα was initially tested using Mardin-darby bovine kidney (MDCK) cells infected with vesicular stomatitis virus (VSV). MDCK cells do not express HLA-A*02 and, therefore, inhibition of VSV replication mediated by IFNα conjugates reflects the intrinsic IFNα activity of the protein conjugates in the absence of targeting. TCR-L/IFNα were much less active in suppressing VSV replication than IFNα2a (Roferon A) and retained only about 3% of IFNα activity on a molar basis (data not shown). We then tested the IFNα biological activity of TCR-L/IFNα on HepG2 cells by analyzing the expression of selected ISGs (MX1, OAS1) by q-PCR or by using an ISRE luciferase reporter system transiently expressed in HepG2 cells.

34 Several strains find more that developed the most pronounced liver injury, C57BL/10J and NZW/LacJ, also exhibited increased levels of Grp78 and Chop and an increase in Chop transcript. Notably, these ER stress markers were not induced consistently in other strains with high liver injury, which suggests that ER stress may not be a requisite event in alcoholic liver disease. Alternatively, it is also likely that selective persistence of ER chaperone and CHOP expression is evidence of failure to adapt to chronic unfolded protein response,42 thus serving as a prodeath factor that exacerbates liver injury caused by alcohol.

ER stress has also been implicated as one of the regulatory mechanisms in hepatocyte lipid metabolism.28 A key interconnectedness between hepatic steatosis and ER stress, including the physiological role of the ER stress protein click here sensors in lipid homeostasis, has been demonstrated in several recent publications.43 In this study we observed an unexpected down-regulation of Srebf1 and lack of induction of Cebpa in strains with high liver injury and liver steatosis. In prior work, up-regulation of SREBP1 and lipogenesis

has been observed, albeit in a mouse strain not studied here. The difference may be related to the severity of ER stress or other unknown factors. A down-regulation of transcription factors involved in lipid synthesis has also been suggested as a sign of failure to adapt to chronic ER stress. For example, steatosis develops in the liver of tunicamycin-treated mice and is associated with unresolved ER stress, prolonged up-regulation of Chop, and inhibition of metabolic master regulators.28 In addition, silencing of SREBP1 in vitro has led to dramatic loss of cell viability by way of induction of apoptosis.44 Most recent studies demonstrated that the decreased SAM/SAH ratio as a consequence of hyperhomocysteinemia appears to have a key role, as it can affect the ratio of phosphatidylcholine to phosphatidylethanolamine in ER membrane that could either lead to increased processing of SREBP145 or ER stress response.46 In Caenorhabditis elegans, decreased

SAM/SAH leads to decreased phosphatidylcholine/phosphatidylethanolamine ratio in ER, resulting in transcription-independent activation of SREBP1 and induction Tenofovir of lipogenesis and one-carbon metabolism.45 However, the latter compensatory attempt to correct SAM/SAH may be impaired by the effects of alcohol. Although the precise mechanism of alcohol-induced effects on one-carbon metabolism remain to be determined and additional studies are needed to further investigate the differences in the role of ER stress in apoptosis and steatohepatitis among susceptible and resistant strains, our data clearly point to the genetic factors that may control adaptation to ER stress as one of the key events in the predisposition to alcoholic liver disease.

2% versus 48.5% in those randomized to 48 weeks). Thus, if an extended 72-week regimen is being contemplated for an individual patient, the decision should be informed by rs12979860 genotype status and should only be generally considered for slow responders who carry a T allele. EPZ 6438 Interest in extended-duration therapy

is waning with the approval of the first direct-acting antiviral agents (DAAs). However, because slow virologic responders have suboptimal response rates to peginterferon/ribavirin/DAA triple therapy,28-31 response-guided therapy remains an important treatment strategy. A response-guided approach was used in the phase 3 studies of protease inhibitors by extending treatment to 48 weeks in patients with detectable HCV RNA at week 4 (telaprevir) or 8 (boceprevir).27,

28 These trials confirmed the potential for these agents to increase overall SVR rates and decrease treatment duration for many genotype 1 patients. A treatment extension beyond week 48 was not investigated so far. It is not clear, however, whether all patients will require a DAA to optimize treatment outcomes. For example, the addition of boceprevir after 4 weeks Selleck Alvelestat of treatment with peginterferon plus ribavirin improved SVR rates only in individuals with a <2-log10 drop in HCV RNA after the 4-week run-in period in a phase 2 study in treatment-naive genotype 1 patients.29 Furthermore, as shown in the present study, regardless of the IL28B genotype more than 80% of patients with an RVR on peginterferon/ribavirin achieve an SVR after just 24 weeks of treatment. Thus, the benefit of adding a DAA to standard peginterferon plus ribavirin therapy in these patients requires further evaluation. Like all published studies on the role of IL28B polymorphism, this analysis was carried out Cytidine deaminase retrospectively. Patients were

recruited for the parent trial between 2003 and 2008, long before the importance of the IL28B genotype in the treatment of chronic hepatitis C was established. Therefore, not all patients who were enrolled in the study were represented in the genotype analysis; thus, the results must be regarded with caution. Patients were recalled and asked to participate in this analysis; thereby only 62.3% of the study participants could be tested. This compares well with other retrospective trials (i.e., 65% in the study by Mangia et al.32 and 52.2% in the study by Thompson et al.17). The overall results of the parent study were not different from this subanalysis. Furthermore, patients were not stratified by rs12979860 genotype. It is reassuring that a similar proportion (≈60% to 67%) of patients were genotyped in each group, and that the relapse rates reported in groups A and B in the original study (33% and 17%, respectively) are generally similar to those reported in this analysis (38% and 19%, respectively).

The studies provided adjusted overall OR estimates for current statin use versus non-use, leading to a pooled OR of 0.86 (95% confidence interval [CI], 0.77–0.97; P < 0.001). The overall OR of population-based case–control studies and cholecystectomy Talazoparib solubility dmso due to gallstone disease were

0.83 (95% CI, 0.73–0.95; P = 0.0131) and 0.78 (95% CI, 0.74–0.82; P = 0.615), respectively. There is evidence that current statin use lowers the risk of gallstone disease compared with non-use, especially for cholecystectomy due to gallstone disease. Low statin use (1–4 prescriptions) did not decrease the risk of gallstone disease, but moderate and high statin use significantly decreased the risk. Further multicenter and better controlled studies are needed to confirm these findings. “
“There are over 500–750 000 deaths per year because of hepatitis B virus (HBV)-related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity NVP-BEZ235 datasheet and a very high prevalence of

smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet

needs for improving HBV prevention and control in the region are highlighted. “
“Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, PR China, 100850 Multipotent stem/progenitors are present in peribiliary glands of extrahepatic acetylcholine biliary trees from humans of all ages and in high numbers in hepato-pancreatic common duct, cystic duct, and hilum. They express endodermal transcription factors (e.g., Sox9, SOX17, FOXA2, PDX1, HES1, NGN3, PROX1) intranuclearly, stem/progenitor surface markers (EpCAM, NCAM, CD133, CXCR4), and sometimes weakly adult liver, bile duct, and pancreatic genes (albumin, cystic fibrosis transmembrane conductance regulator [CFTR], and insulin). They clonogenically expand on plastic and in serum-free medium, tailored for endodermal progenitors, remaining phenotypically stable as undifferentiated cells for months with a cell division initially every ≈36 hours and slowing to one every 2-3 days.