Intestinal decontamination with non-absorbable antibiotics restored eubiosis, decreased intestinal inflammation and permeability, and reduced

alcoholic liver disease in mice suggesting that alcohol-associated dysbi-osis induces intestinal inflammation and leakiness. To further define the role of TNFα in mediating intestinal barrier dysfunction following alcohol administration, we focused on the main receptor for TNFα, TNF-receptor 1 (TNFR-1). TNFR-1 mutant mice (TNFR-1flxneo/flxneo) were protected from intestinal barrier dysfunction as evidenced by higher levels of fecal albumin and decreased hepatic contents of bacterial products. TNFR-1 mutant mice had less liver disease as shown by lower plasma ALT levels and hepatic triglycerides. To investigate click here whether TNFR-1 on intestinal epithelial cells mediates intestinal barrier dysfunction and liver disease, a functional TNFR-1 was selectively expressed https://www.selleckchem.com/products/icg-001.html on intestinal epithelial cells

by crossing TNFR-1flxneo/flxneo mice with Villin-Cre transgenic mice. Reactivation of TNFR-1 on enterocytes resulted in increased intestinal permeability and liver disease that is similar to wild type mice after alcohol feeding, suggesting that enteric TNFR-1 promotes intestinal barrier dysfunction and mediates alcoholic liver disease. Myosin light chain kinase (MLCK) is a downstream target of TNFα and was phosphorylated in intestinal epithelial cells following alcohol administration. Intestinal barrier loss was reduced in click here MLCK−/− mice after ch ronic alcohol feeding. While hepatic steatosis was lower in MLCK−/− mice as compared with wild type mice, liver injury was not reduced suggesting that intestinal MLCK partially

contributes to intestinal leakiness and liver disease. Conclusion: Dysbiosis-induced intestinal inflammation and TNFR-1 signaling in intestinal epithelial cells are mediating a disruption of the intestinal barrier following chronic alcohol feeding. Therefore, intestinal TNFR-1 is a crucial mediator of alcoholic liver disease. Disclosures: Samuel B. Ho – Consulting: Genentech; Grant/Research Support: Roche The following people have nothing to disclose: Peng Chen, Peter Starkel, Jerrold R. Turner, Bernd Schnabl Alcoholic liver disease is a major health issue worldwide, but effective therapies are currently unavailable. The present study tested the efficacy of Alda-1, an activator of aldehyde dehydrogenase 2, in treating alcoholic liver disease. Male C57BL/6J mice were exposed to alcohol for up to 8 weeks for a time-course study on aldehyde metabolism. The effects of Alda-1 on aldehyde dehydrogenase 2 and aldehyde clearance were determined after acute alcohol intoxication. Mice were exposed to alcohol for 8 weeks with or without Alda-1 administration for the last 10 days to test the therapeutic potential of Alda-1.

Accordingly, a decline of HBV-DNA means reduction of HBV replication. In contrast, HBsAg can be derived from both mature virions and defective particles. Thus serum HBsAg level not only reflects the cccDNA transcription

or mRNA translation, but also host immune control over HBV infection.[54, 55] The relationships between qHBsAg, intrahepatic HBV-DNA, and serum HBV-DNA concentration have been analyzed recently. In HBeAg-positive CHB, qHBsAg positively correlated with intrahepatic HBV-DNA and serum HBV-DNA concentration.[56, 57] On the contrary, qHBsAg correlated poorly with serum HBV-DNA and did not correlate with intrahepatic screening assay HBV-DNA in HBeAg-negative CHB.[57] With regard to clinical phenotypes, qHBsAg was much higher in HBeAg-positive patients with immune tolerance and immune clearance phases than HBeAg-negative patients.[58, 59] An Italian study showed that the combination of qHBsAg < 1000 IU/mL and serum HBV-DNA level < 2000 IU/mL can predict inactive HBV carrier state with a positive predictive value of 88% and negative predictive value of 97% in HBV genotype D patients.[60] Our recent study also showed that low serum levels of HBsAg (< 100 IU/mL), alone or in combination with HBV-DNA levels, at 1 year after HBeAg seroconversion could

predict HBsAg loss in patients with HBV genotype B or C infection.[61] In addition, qHBsAg was better than serum HBV-DNA level for the prediction of spontaneous HBsAg loss in HBeAg-negative carriers with a low viral load (< 2000 IU/mL). HBsAg level < 10 IU/mL was the strongest predictor of HBsAg loss in patients with a low viral C1GALT1 load.[62] The earlier Trichostatin A manufacturer lines of evidence indicate that there exists a correlation between qHBsAg and liver disease progression. In the recent update of REVEAL-HBV study, qHBsAg was analyzed in 3411 HBV carriers. The results showed that both HBsAg and HBV-DNA levels are independent predictors of HCC development. The multivariate-adjusted HR of developing HCC increased significantly from 1.0 (reference) for serum levels of HBV-DNA (IU/mL)/HBsAg (IU/mL) of < 2000/< 100

to 9.22 (95% CI: 4.34–19.58) for serum levels of HBV-DNA (IU/mL)/HBsAg (IU/mL) of ≥ 2000/≥ 100.[63] Our hospital-based Elucidation of Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers (ERADICATE-B) study (Fig. 1) also showed similar findings. A total of 2688 non-cirrhotic Taiwanese CHB patients were followed for a mean of 14.7 years. HCC risk increased when patients had increased HBV-DNA level (HR: 4.7; 95% CI: 2.2–10.0), increased qHBsAg (HR: 7.2; 95% CI: 1.8–28.6), and elevated ALT level (HR: 6.6; 95% CI: 2.2–19.8).[64] Although the incidence of HCC is significantly associated with baseline serum HBV-DNA levels in a dose–response relationship,[6, 49, 64] inactive or low-risk HBV carriers (serum HBV-DNA levels < 2000 IU/mL) still have significantly higher HR for HCC compared with individuals without HBV infection (HR: 4.6; 95% CI: 2.5–8.3).

1C). Given the findings that the absence of HO-1 activity impaired liver regeneration and survival, we next speculated that one of the products of HO-1 activity would likely influence regeneration. We therefore hypothesized that CO, which is known to exert protective effects in the liver, as well as impact cellular proliferation, would modulate liver regeneration and hepatocyte proliferation following hepatectomy. We harvested www.selleckchem.com/GSK-3.html liver samples over time following hepatectomy from mice treated with or without CO and stained multiple sections with anti-phospho histone 3 (pH3) antibody, which exclusively stains proliferating

cells.24 H3 phosphorylation (specifically serine 10) is directly correlated with the induction of immediate-early gene expression and proliferation.25 The percentage of pH3-positive hepatocytes at 24 hours in CO-treated mice (11.0 ± 5.12%) was significantly higher than in air controls (3.74 ± 1.22%; Fig. 1D-G,M), which otherwise peaked at 36-48 hours. To validate our pH3 staining measuring proliferation, we stained the same liver sections as above

with anti-Ki67 as a marker of DNA synthesis. CO-treated mice again showed earlier activation of DNA synthesis 24 hours after PHTx versus control (17.34% ± 2.68% versus 7.34% ± 3.19% in air controls; P < 0.05; Fig. 1H-K). After PF-6463922 purchase PHTx, the percentage of Ki-67-positive cells increased and peaked at 48 hours in both air and CO-treated mice and returned to baseline by 7-10 days (Fig. 1L). Given the higher proliferative rate in CO-treated mice, we next measured alterations in liver function following PHTx by measuring prothrombin time

(PT) and calculating an international normalized ratio (INR) by comparing the PT in naïve animals. The PT-INR was measured in animals after 70% PHTx in the presence Palbociclib or absence of CO. Air-treated animals showed a 2-fold increase in PT-INR 24 hours after PHTx, indicative of a significant loss of function, whereas CO-treated, PHTx animals maintained a normal PT-INR and normal phosphate levels, suggesting overall improved function (Fig. 2A,B). PT-INR returned to baseline levels by day 3 in both groups (data not shown). These findings suggest that CO can prevent loss of liver function after PHTx and contribute in part to maintaining or enhancing early recovery after PHTx (Fig. 1). Serum alanine aminotransferase (ALT) is used as a liver function test assessing hepatocyte damage. We observed an expected increase in ALT in both air and CO-treated animals peaking at 12 hours, with no difference between CO and air at any timepoint evaluated (Fig. 2C). Why CO had no effect on the increase in ALT posthepatectomy is not clear, but the elevation in ALT has been observed by others and is inherent to the model.15 We next examined the effect of CO exposure on the general behavior and health of the mice by monitoring body weight changes following PHTx. Air-treated mice lost weight steadily from days 1 to 3 before beginning to gain starting on days 4-5.

28-0.64-μm size range in mediating ALF syndrome. The direct correlation between MP number and factor VIII levels also suggests that MPs may play a role in vascular endothelial cell activation/injury of ALF, the severity of which directly correlates with mortality.10, 33 Whether MPs serve as mediators of the systemic complications of ALF or are simply biomarkers of inflammation cannot be determined Apoptosis antagonist conclusively from our data; however, it appears likely that they represent both the cause and the effect of systemic inflammation. Recent studies have

also incriminated MPs in the pathogenesis of chronic liver diseases (CLDs).30 Patients with cirrhosis have increased circulating MPs derived from leukocytes, ECs, and hepatocytes, compared to healthy controls, and concentrations of MPs increase with increasing severity of cirrhosis.20 MPs isolated from PPP of subjects with cirrhosis were shown in vitro and in experimental animals to impair Deforolimus manufacturer vasoconstrictor response and may thereby cause the vasoplegia of end-stage liver disease. Similarly, T-lymphocyte-derived CD4+ and CD8+

MP numbers were higher in patients with nonalcoholic fatty liver disease and chronic hepatitis C than healthy controls and correlated with disease activity.34, 35 In contrast to the present work, the number of CD41+ (platelet-derived) MPs in these populations with CLD were not significantly higher than healthy controls nor were they proportional to the severity of disease. However, both of these studies were performed using flow cytometry and

may have thereby missed a possible effect of platelet-derived MPs, most of which (as shown herein) are below the limit of detection by flow cytometry. These studies and the present work suggest that increased production of platelet MPs may be restricted to acute conditions characterized by a prominent SIRS. In addition to systemic effects of MPs implied by the association of MP concentrations and systemic complications of ALF, procoagulant MPs may also Cytidine deaminase serve to exacerbate the primary liver injury. In a mouse model of APAP hepatotoxicity, activation of coagulation within the necrotic liver increases the primary APAP-induced injury and is greatly ameliorated by heparin administration.7 Furthermore, the prothrombotic effect of APAP is also greatly ameliorated in mice expressing low levels of TF, providing indirect evidence that liver-derived TF may mediate the activation of coagulation.7 Other experimental models also support a role for secondary activation of coagulation within the acutely injured liver in the pathogenesis of liver failure.36, 37 Because thrombin generation requires exposure of anionic phospholipids on cellular and/or MP surfaces, intrahepatic MPs would be reasonable candidate platforms on which coagulation occurs. MP-TF assays have also shown that the population of circulating MPs is highly procoagulant in a TF-dependent manner.

Thus, iPSCs could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient-specific disease modeling. Here, we describe an efficient

and rapid three-step protocol that is able to rapidly generate hepatocyte-like cells from human iPSCs. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC-derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme Y-27632 cell line activity, secreted urea, uptake of low-density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocyte-like cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficient mouse model. Conclusion: We have established a rapid

and efficient differentiation protocol that is able to generate functional hepatocyte-like cells from human iPSCs. This may offer an alternative option for treatment of liver diseases. (Hepatology 2012) Viral hepatitis or drugs often cause liver injury and cirrhosis. Fenbendazole Liver transplantation is the only effective treatment for end-stage liver diseases1; however, serious side effects of chronic immunosuppression https://www.selleckchem.com/products/poziotinib-hm781-36b.html and lack of suitable donor livers are major obstacles to liver transplantation. Reprogramming of mouse and human somatic cells to become induced pluripotent stem cells (iPSCs) has recently been achieved by viral transduction using four transcription factors.2 Unlike human embryonic stem (ES) cells, human iPSCs provide an alternative approach that

avoids the controversies associated with the use of human embryos to obtain pluripotent ES cells. Although their gene expression pattern is not identical to human ES cells,3 human iPSCs are pluripotent and able to differentiate into most, if not all, cell types of the body. Therefore, human iPSC-derived somatic cells, such as hepatocytes, would be able to serve as an alternative source for liver transplantation, as well as help with toxicity screening during drug discovery. During embryonic development, epiblast cells receive sequential developmental cues and undergo epithelial-to-mesenchymal transition to generate mesoderm or definitive endoderm.4 Several studies have successfully generated hepatocyte-like cells from human ES cells5-11 and human iPSCs12-17in vitro. Most of these studies have focused on how to develop an efficient differentiation protocol with which to generate functional hepatocyte-like cells.

Then we validated the implicated variants in expanded additional cases including patients with CD, UC and healthy controls. Results: We uncovered 294 shared complete identical variants in four Chinese CD patients, of which 26 were validated with Sanger sequencing. Further analyzed the differences of genotype frequency between cases and controls, we detected 3 variants (IFNA10 c.60 T > A, IFNA4 c.60 T > A, PMS2P3 c.67 C > T) are associated

with susceptibility to CD. The variants of IFNA10 and IFNA4 were significantly associated Alvelestat with resistance of steroids treatment in CD patients. Conclusion: We performed the exome-wide screening for the causative germline variants in Chinese Crohn’s disease patients, identified

three of new candidate gene variants of CD. These candidate genes may provide a clue to understand the genetic heterogeneity of CD and lead to better screening and improvement of treatment. Key Word(s): 1. CD; 2. exome sequencing; 3. susceptible gene; Presenting Author: METIN BASARANOGLU Corresponding Author: METIN BASARANOGLU Affiliations: TC Ankara Yüksek Ihtisas Hospital Objective: The development of colonic stenosis is a complication of Crohn’s disease (CD). We, here, presented a case with a long right colon and 2 short segment colonic stenosis diagnosed by barium follow through and colonoscopy and treated by 18 months adalimumab injection therapy and find more followed-up by clinically and radiologically. Methods: A 24-year-old male was admitted to our inflammatory bowel diseases clinic 11 years ago. His complaints were abdominal Calpain pain and bloody diarrhea. Further investigations showed Crohn’s ileo-colitis. Oral mesalazine 4 g/day and azotiopürine 125 mg/day was started. However, a few months later, he stopped to use azotiopürine. Nine

years ago, he was re-admitted with abdominal pain and diarrhea without bleeding. Careful examinations were performed. Then, oral mesalazine, azotiopürine plus short term steroid were started. Results: Four years ago, he stopped to use azotiopürine because of sperm quality and number. Three years ago, he defined abdominal with fever. His condition was not good. Colonoscopy failed because of active mucosal inflammation and non-obstructive stenosis in sigmoid colon. He again refused to use immunosüpresive agents. Two years ago, he was hospitalized because of abdominal pain, fever and bloody diarrhea. Abdominal tomograpy showed that the wall of the colon was thickened, particularly in the right colon with 22 mm, 12 mm in transvers colon and 9 mm in sigmoid colon. Small bowel contrast examination tickened distal ileum wall. Double contrast examination of the colon showed 3 strictures which involved in transvers, right and sigmoid colon (fig. 1 and fig. 2). The lenghts of the stricture were 3 cm, 6 cm and 2 cm, respectively.

38 Transcomplementation of HBx protein with hydrodynamic injection restored HBV infectivity in mice. Interestingly, all revertant viruses show a restored ability to express HBx.38 By infecting chimeric mice with genotype A, B and C, differing proliferative capacity has been shown between HBV genotypes.37 In mice infected for a relatively short time, there are no morphological changes in HBV infected mice livers in https://www.selleckchem.com/products/MDV3100.html studies.13,36 In contrast, the occurrence of liver cell damage has been reported after long-term infection of chimeric mice with HBV39 or with specific strains of HBV;40 these findings are consistent with direct cytopathic effects of HBV under certain conditions. The biological properties of a newly

identified unique strain of HBV, genotype G, which replicates only in the presence of another genotype, were confirmed using the chimeric mouse.41 Infectivity of another

novel HBV strain, identified from a Japanese patient, that is divergent from known human and ape HBV has also been confirmed.42 Titration of HBV infectivity, which previously could only be carried out using chimpanzees, can be carried out effectively using chimeric mice.43 Taking advantage of the absence of human immune cells in the chimeric mice, Noguchi et al.44 showed that hypermutation of HBV increases in human hepatocytes under interferon treatment. Dandri et al. measured viral half-life in human and chimeric mice repopulated with wooly monkey hepatocytes.45 The results clearly showed that viral half-life is shortened by immunological

mechanisms in humans with low viral levels, but not in chimeric mice where functional selleck chemicals llc immunity is absent. Hiraga et al.46 showed an absence of interference between HBV and HCV. Evaluation of therapeutic agents is the most important role for this mouse model. Tsuge et al.13 assessed the effect of interferon and lamivudine using chimeric mice. Similarly, Dandri et al.47 showed the effects of adefovir using uPA/scid mice repopulated with tupaia hepatocytes, which also support replication of human HBV. Oga et al.48 identified a novel lamivudine-resistant variant that has an amino acid substitution outside of the YMDD motif. They showed that lamivudine was ineffective against the novel mutant Calpain strain. It is thus apparent that this mouse/human liver chimeric model is ideal to study the susceptibility of mutant strains to various drugs, because mutant viruses can easily be made and infected into chimeric mice.13 The model has also been utilized to evaluate viral entry inhibitors derived from the large envelope protein.49 As observed in studies on HBV, HCV infection efficiency was poor and levels of viremia were low in mice where the repopulation rate of the mouse liver with human hepatocyte was low.17,50 As shown in Figure 3, human albumin levels in mouse serum were significantly higher in mice in which measurable viremia developed (Hiraga et al. unpublished data).

Extracts were prepared from snap-frozen liver by homogenization in lysis buffer

(Tris-HCl 50 mM, NaCl 150 mM, ethylenediaminetetraacetic acid 1 mM, 1% Triton X-100, 0.5% Tween-20, and 0.1% sodium dodecyl sulphate), containing a protease-inhibitor cocktail (Roche), followed by centrifugation at 14,000×g for 15 minutes at 4°C. Supernatants were collected and activated with acetic acid/urea before analysis. Transforming growth factor β (TGFβ1) content of liver protein extracts were measured using a mouse TGFβ1 enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems, Inc., Minneapolis, MN). Plates were read using the Bio-Rad (Hercules, DAPT research buy CA) microplate reader at 450 nm (with a 540-nm reference filter), and TGFβ1 concentrations were calculated from the standard

curve by the plate-reader software. Immortalized human HSCs (LX-2 cells; a gift from Dr. Scott Friedman) were seeded for 3 days into six-well plates at a density of 1 × 105 cells per well in M199 medium (Gibco, Grand Island, NY) with 5% fetal calf serum. Media were changed at day 3, and human PAR-1 agonist hexapeptide SFLLRN-NH2 (Sigma-Aldrich) and/or human PAR-2 agonist hexapeptide SLIGKV (Sigma-Aldrich) were added at varying concentrations. A scrambled hexapeptide (Auspep, Melbourne, Victoria, Australia) was used as a control. A further dose of either agonist or scrambled peptide was added at 24 and 48 hours, and culture medium and cells were harvested after 72 hours of peptide exposure. The collagen content of the cell-culture supernatant was measured using Dapagliflozin the Sircol Sirius red Apoptosis Compound high throughput screening dye colorimetric assay (Biocolor, Newtown Abbey, Northern Ireland), as previously described,11 and TGFβ1 content was measured by ELISA. LX-2 cells were seeded onto 96-well plates at a density of 1 × 104 per well in 5% FCS/M199 media and

cultured overnight. The PAR-2 agonist peptide, SLIGKV, was added at concentrations from 0 to 100 μM at 24 and 48 hours. Human platelet-derived growth factor (PDGF)-BB (R&D Systems, Minneapolis, MN) was used as a positive control at a concentration of 25 ng/mL. Proliferation of activated HSCs was assessed using a colorimetric bromodeoxyuridine ELISA (Roche), according to the manufacturer’s instructions. Data are expressed as mean ± standard error of the mean. Statistical significance was determined by one-way analysis of variance with the Newman-Keuls post-test for multiple comparisons or the Student’s t test for comparisons between two groups, as appropriate, using GraphPad Prism 5.03 for Windows (GraphPad Software, Inc., La Jolla, CA). WT mice developed significant hepatic collagen deposition in response to CCl4 administration (Fig. 1A). No fibrosis was observed in WT mice given olive oil alone (data not shown). Quantitative analysis of histological fibrosis by computer-assisted morphometry in CCl4-treated WT mice showed marked fibrosis at 5 weeks (1.97% ± 0.

Scott Publication Fund. Many thanks to everyone at DOC who assisted in the field and with sampling of carcasses, especially C. Duffy, G. Hickman, K. Hillock, C. Lilley, K. MacLeod, and B. Williams; to N. Gibbs for collecting the Wellington Harbour biopsy sample; BKM120 mouse to those involved with the current and baseline labwork: A. Alexander, E. Carroll, D. Heimeier, S. Lavery, F. Pichler, K. Russell, D. Steel, K. Thompson, and M. Vant; and to V.

Ward for the Hector’s dolphin drawing. We are grateful for support from local iwi and DOC Area Offices and Conservancies. We also thank M. Schwartz and three anonymous reviewers for comments to improve the manuscript. Biopsy samples were collected under permit RNW/HO/2009/03 issued to CSB from DOC and the protocol AEC/02/2008/R658 approved by the University of Auckland Animal Ethics Committee. “
“Humpback whales (Megaptera novaeangliae) migrate long distances each year on a return journey from low-latitude breeding grounds to high-latitude feeding grounds. Migration is influenced selleck inhibitor by subtle and complex social behaviors

and the assumption that whales transit directly through the migratory corridor off the east coast of Australia requires further investigation. From 2003 to 2005, we followed the movements of 99 individual whales within one migratory cycle from three locations, off Byron Bay during the whales’ northern migration and in Hervey Bay and at Ballina during the southern migration. The median sighting interval of whales between Byron Bay and Hervey Bay (n = 26) was 52 d (IQR = 42.5–75.5); between Byron Bay and Ballina (n = 21) was 59 d (IQR = 47.0–70.0); and between Hervey Bay and Ballina (n = 33) was 9 d (8.0–14.0). The overall pattern observed from these resightings suggests that Group E1 humpback whales spend approximately two months in the northern quarter of their range during the austral winter months. Intraseason resightings of whales at Ballina (n = 13, median sighting interval = 7 d) also suggest that some individuals,

particularly adult males, may circle back north during their general southward journey along this part of the coast, perhaps in an attempt to increase mating opportunities. “
“South Australian Museum, Adelaide, South Australia , Australia CHIR-99021 “
“We studied life history characteristics of the Hong Kong/Pearl River Estuary population of Indo-Pacific humpback dolphins (Sousa chinensis), based on data from 120 specimens stranded between 1995 and 2009, 40 individuals biopsied at sea, and a long-term (14+ yr) photo-identification study. Ages were determined for 112 specimens by thin-sectioning teeth and counting growth layer groups. Estimated length at birth was 101 cm. Longevity was at least 38 yr, and there was little difference in growth patterns of males and females. Growth was described by a Bayesian two-phase Gompertz model; asymptotic length was reached at 249 cm. The tooth pulp cavity filled at an average of 18.

Recent advances provide additional support for the liver TISC concept and, importantly, may aid therapeutic decision making by allowing risk assessment. Targeted anti-TISC therapies hold significant promise, but a better understanding of the origin and phenotype of Rapamycin these cells appears necessary. Significant progress has been made in liver stem cell and liver cancer

stem cell research in the last 2 years. Although normal and cancerous liver stem cells or LPCs naturally share many characteristics and markers, on most accounts, the two fields have been moving forward independently. The dual focus of the conference provided an opportunity to gather insight or update one’s knowledge of the other field. In addition, the conference

identified commonalities that may serve as a basis for future advances. For selleck screening library example, new markers of normal LPCs may be useful for further fractionation of heterogeneous TISC populations. Conversely, signaling pathways and transcription factors regulating TISC characteristics may also play a role in noncancerous liver regeneration. In addition, new cell-culture or in vivo cell-delivery systems will likely benefit research on both normal and cancerous liver stem cells or LPCs. The hope is that increased exchange and collaboration between the two fields will accelerate the development of therapies for patients with liver disease and liver cancer. The American Association for the Study of Liver Disease Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” was held in Atlanta, GA, March 19-20, 2011. The meeting provided an overview and update on ongoing research efforts seeking to obtain a detailed

understanding of stem cell biology in liver disease and cancer for the development of new therapies. This review is dedicated to Nelson Fausto, a leader in the field. “
“Ischemia-reperfusion injury (IRI) is a major limiting event for successful GPCR & G Protein inhibitor liver transplantation, and CD4+ T cells and invariant natural killer T (iNKT) cells have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect liver grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) and wildtype (WT) mouse livers were transplanted into WT recipients after 18 hours cold storage and pathological analysis was performed 6 hours after transplantation. Serum levels of alanine aminotransferase and interleukin (IL)-6 were significantly reduced in recipients of CD39tg livers compared to recipients of WT livers. Furthermore, less severe histopathological injury was demonstrated in the CD39tg grafts. Immune analysis revealed that CD4+ T cells and iNKT cells were significantly decreased in number in the livers of untreated CD39tg mice.