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| 1 | Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis显示文摘Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments. | Yaron Ilan | 2012 | World Journal of Gastroenterology2012，18，21： | 17 |
| 2 | Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: Results of a phase Ⅰ clinical trial显示文摘AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins(CEP) in Crohn's disease (CD) subjects.METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels.RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CDS+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period.CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation. | Eran Israeli Eran Goldin Oren Shibolet Athalia Klein Nilla Hemed Dean Engelhardt Elazar Rabbani Yaron Ilan | 2005 | World Journal of Gastroenterology2005，11，20： | 8 |
| 3 | Point-of-care continuous ^(13)C-methacetin breath test improves decision making in acute liver disease: Results of a pilot clinical trial显示文摘AIM: To assess the role of the 13C-methacetin breath test (MBT) in patients with acute liver disease. METHODS: Fifteen patients with severe acute liver disease from diverse etiologies were followed-up with 13C-MBT during the acute phase of their illnesses (range 3-116 d after treatment). Patients fasted for 8 h and ingested 75 mg of methacetin prior to the MBT. We compared results from standard clinical assessment, serum liver enzymes, synthetic function, and breath test scores. RESULTS: Thirteen patients recovered and two patients died. In patients that recovered, MBT parameters improved in parallel with improvements in lab results. Evidence of consistent improvement began on day 3 for MBT parameters and between days 7 and 9 for blood tests. Later convergence to normality occurred at an average of 9 d for MBT parameters and from 13 to 28 d for blood tests. In both patients that died, MBT parameters remained low despite fluctuating laboratory values. CONCLUSION: The 13C-MBT provides a rapid, noninvasive assessment of liver function in acute severe liver disease of diverse etiologies. The results of this pilot clinical trial suggest that the MBT may offer greater sensitivity than standard clinical tests for managing patients with severe acute liver disease. | Gadi Lalazar Tomer Adar Yaron Ilan | 2009 | World Journal of Gastroenterology2009，15，8： | 6 |
| 4 | Gastric stimulation for weight loss显示文摘The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation(GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity. | Meir Mizrahi Ami Ben Ya'acov Yaron Ilan | 2012 | World Journal of Gastroenterology2012，18，19： | 4 |
| 5 | Oral administration of a non-absorbable plant cellexpressed recombinant anti-TNF fusion protein induces immunomodulatory effects and alleviates nonalcoholic steatohepatitis显示文摘AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein(PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS.RESULTS The orally administered non-absorbable PRX-106 w a s b i o l o g i c a l l y a c t i v e. A l t e r e d d i s t r i b u t i o n o f CD4+CD25+Fox P3+ between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4+CD25+Fox P3+ ratio and a decrease in the intrasplenic-to-intrahepatic CD8+CD25+Fox P3+ ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic-to-intrahepatic NKT ratio were noted. Assessment of the CD4-to-CD8 ratios showed sequestration of CD8+ lymphocytes in the liver. These effects were associated with a decrease in serum triglyceride levels, decrease in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice.CONCLUSION Orally administered PRX-106 shows biological activity and exerts an immunomodulatory effect, alleviating liver damage. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis. | Yaron Ilan Ami Ben Ya'acov Yehudit Shabbat Svetlana Gingis-Velitski Einat Almon Yoseph Shaaltiel | 2016 | World Journal of Gastroenterology2016，22，39： | 3 |
| 6 | Oral mixture of autologous colon-extracted proteins for the Crohn's disease: A double-blind trial显示文摘AIM: To evaluate the safety and efficacy of oral administration of AlequelTM, an autologous proteincontaining colon extract.a randomized,placebo-controlled,double-blind trial.Patients were orally administered with autologous protein-containing colon extract three doses of autologous study drug per week for 15 wk,for a total of45 doses.Patients were followed for safety parameters.Remission was defined as a Crohn’s disease activity index(CDAI)score of less than or equal to 150.All patients were followed for changes in subsets of T cells by fluorescence-activated cell sorting analysis.RESULTS:Analysis was performed on a total number of evaluable patients of 14 in the study drug group and15 in the placebo group.Treatment was well tolerated by all patients.No major treatment-related adverse events were reported or observed in any of the treated patients during the feeding or follow-up periods.Between weeks 6 and 9 of the study,six of the 14(43%)evaluable subjects who received the study drug achieved a CDAI of 150 or lower.In contrast,five of the 15(33%)evaluable subjects in the placebo group achieved remission.Between weeks 9 and 12,the remission rates were 50%and 33%for the drug group and placebo group,respectively.Among the drug-treated subjects who achieved remission,the effect of the drug was judged as stable in eight of the 14 subjects as measured by at least two CDAI scores indicating remission in the 15-wk treatment period.A decreased percentage of peripheral natural killer T regulatory cells(a decrease of 28%vs an increase of 16%)and an increased ratio of CD4+/CD8+T lymphocytes(an increase of 11%vs a decrease of9%)were noted in subjects with a significant clinical response.CONCLUSION:Oral administration of the autologous colonic extract could be a safe and effective for the treatment of patients with moderate to severe Crohn’s disease. | Eran Israeli Ehud Zigmond Gadi Lalazar Athalia Klein Nilla Hemed Eran Goldin Yaron Ilan | 2015 | World Journal of Gastroenterology2015，21，18： | 3 |
| 7 | Antioxidant therapy for chronic hepatitis C after failure of interferon:Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial显示文摘AIM:TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus(HCV) infection. METHODS:One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo,or oral treatment alone. Primary end points were liver enzymes,HCV-RNA levels and histology. RESULTS:Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo(P= 0.05).Histology activity index(HAI)score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo(P=0.21).HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo(P=NS).In partⅡof the trial,oral administration of antioxidants was not associated with significant alterations in any of the end points. CONCLUSION:Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients. | Ezra Gabbay Ehud Zigmond Orit Pappo Nila Hemed Mina Rowe George Zabrecky Robert Cohen Yaron Ilan | 2007 | World Journal of Gastroenterology2007，13，40： | 2 |
| 8 | A Novel 13C-Urea Breath Test Device for the Diagnosis of Helicobacter pylori Infection: Continuous Online Measurements Allow for Faster Test Results With High Accuracy显示文摘 | Eran Israeli Yaron Ilan Shimon Bar Meir Claudia Buenavida Eran Goldin | 2003 | Journal of Clinical Gastroenterology2003，，： | 1 |
| 9 | Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis显示文摘Natural killer T lymphocytes (NKT) have been implicated in the regulation of autoimmune processes in both mice and humans. In response to stimuli, this subset of cells rapidly produces large amounts of cytokines thereby provoking immune responses, including protection against autoimmune diseases. NKT cells are present in all lymphoid compartments, but are most abundant in the liver and bone marrow. They are activated by interaction of their T-cell receptor with glycolipids presented by CD1d, a nonpolymorphic, major histocompatibility complex class I-like molecule expressed by antigen presenting cells. Several possible ligands for NKT cells have recently been suggested. β-glucosylceramide, a naturally occurring glycolipid, is a metabolic intermediate in the anabolic and catabolic pathways of complex glycosphingolipids. Like other β-glycolipids, β-glucosylceramide has an immunomodulatory effect in several immune mediated disorders, including immune mediated colitis. Due to the broad impact that NKT cells have on the immune system, there is intense interest in understanding how NKT cells are stimulated and the extent to which NKT cell responses can be controlled. These novel ligands are currently being evaluated in animal models of colitis. Here, we discuss strategies to alter NKT lymphocyte function in various settings and the potential clinical applications of natural glycolipids. | Madi El Haj Ami Ben Ya'acov Gadi Lalazar Yaron Ilan | 2007 | World Journal of Gastroenterology2007，13，44： | 1 |
| 10 | Treatment of Chronic Hepatitis C Virus Infection via Antioxidants: Results of a Phase I Clinical Trial显示文摘 | Alla Melhem Mirela Stern Oren Shibolet Eran Israeli Zvi Ackerman Orit Pappo Nilla Hemed Mina Rowe Hana Ohana George Zabrecky Robert Cohen Yaron Ilan | 2005 | Journal of Clinical Gastroenterology2005，，8： | 1 |
| 11 | Reduced liver cell death using a bandage of alginate scaffold: A novel approach for liver reconstruction after extended partial hepatectomy显示文摘 | Eyal Shteyer Ami Ben Ya’acov Lidia Zolotaryova Avital Sinai Yoav Lichtenstein Orit Papoo Olga Kryukov Tsiona Elkayam Smadar Cohen Yaron Ilan | 2014 | Acta Biomaterialia2014，，： | 1 |
| 12 | Late cytomegalovirus disease following liver transplantation显示文摘 | Oren Shibolet Yaron Ilan Yosef Kalish Rifaat Safadi Yaffa Ashur Ahmed Eid Daniel Shouval Dana Wolf | 2002 | Transplant International2002，，12： | 1 |
| 13 | Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC显示文摘 | Alaa Melhem Nidal Muhanna Amal Bishara Carlos E. Alvarez Yaron Ilan Taiser Bishara Amjad Horani Mithal Nassar Scott L. Friedman Rifaat Safadi | 2006 | Journal of Hepatology2006，，1： | 1 |
| 14 | Reduced dose and duration of peginterferon alfa-2b and weight-based ribavirin in patients with genotype 2 and 3 chronic hepatitis C显示文摘 | Michael Manns Stefan Zeuzem Ajit Sood Yoav Lurie Markus Cornberg Hartwig Klinker Peter Buggisch Martin R?ssle Holger Hinrichsen Ismail Merican Yaron Ilan Stefan Mauss Saif Abu-Mouch Andryes Horban Thomas H. Müller Christoph Welsch Rongdean Chen Rab Faruqi | | Journal of Hepatology0，，： | 1 |
| 15 | NK 1.1+ T Cell: A Two-Faced Lymphocyte in Immune Modulation of the IL-4/IFN-γ Paradigm显示文摘 | Shivti Trop Yaron Ilan | 2002 | Journal of Clinical Immunology2002，，5： | 1 |
| 16 | Assessment of liver function in acute or chronic liver disease by the methacetin breath test: a tool for decision making in clinical hepatology显示文摘 | Gadi Lalazar Yaron Ilan | 2009 | Journal of Breath Research2009，，4： | 1 |
| 17 | Intrahepatic CD8^+ lymphocyte trapping during tolerance induction using mushroom derived formulations:A possible role for liver in tolerance induction显示文摘AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis. METHODS: Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay. RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by signifi cant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8+ lymphocyte trapping,demonstratedby an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction. CONCLUSION: Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis. | Mony Shuvy Tiberiu Hershcovici Lidya Zolotarov Yaron Ilan Cristina LulI-Noguera Harry Wichers Ofer Danay Dan Levanon | 2008 | World Journal of Gastroenterology2008，14，24： | 0 |
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