The Experts below are selected from a list of 3345 Experts worldwide ranked by ideXlab platform

Cecilia Zazueta - One of the best experts on this subject based on the ideXlab platform.

  • ellagic acid pharmacological activities and molecular mechanisms involved in Liver Protection
    Pharmacological Research, 2015
    Co-Authors: Wylly Ramses Garcianino, Cecilia Zazueta
    Abstract:

    Abstract Traditional drugs or therapies rarely have effects on regression of chronic Liver diseases, which result in many cases from sustained oxidative stress. In recent years, ellagic acid (EA) has gained attention due to its multiple biological activities and several molecular targets. This is the first review focused on the pharmacological properties and on the molecular mechanisms activated by EA in terms of Liver Protection. EA possesses antioxidant, antihepatotoxic, antisteatosic, anticholestatic, antifibrogenic, antihepatocarcinogenic and antiviral properties that improves the hepatic architectural and functions against toxic and pathological conditions. The molecular mechanisms that EA activates include the scavenging of free radicals, regulation of phase I and II enzymes, modulation of proinflammatory and profibrotic cytokines synthesis, the regulation of biochemical pathways involved in the synthesis and degradation of lipids as well as the maintenance of essential trace elements levels. EA also inhibits hepatic stellate cells and mast cells activation, the proliferation of transformed cells, as well as viral replication by increasing antioxidant response, induction of apoptosis, downregulation of genes involved in cell cycle and angiogenesis, and stimulation of cellular immune response. Despite the enormous therapeutic potential of EA as an innovative pharmacological strategy, the number of phase I and II trials in patients is scarce, precluding its clinical application. In these sense, the use of new deLivery systems that enhances EA bioavailability would improve the results already obtained. Also it remains to be determined if treatment with urolithins instead of EA would represent a better strategy in hepatic disease treatment.

C Trautwein - One of the best experts on this subject based on the ideXlab platform.

  • the il 6 gp130 stat3 pathway in hepatocytes triggers Liver Protection in t cell mediated Liver injury
    Journal of Clinical Investigation, 2005
    Co-Authors: Christian Klein, Torsten Wustefeld, Ulrike Assmus, Tania Roskams, Stefan Rosejohn, Michael Muller, Michael P Manns, Mattias Ernst, C Trautwein
    Abstract:

    Increasing evidence demonstrates that IL-6 has a protective role during Liver injury. IL-6 activates intracellular pathways via the gp130 receptor. In order to identify IL-6–gp130 pathways involved in mediating Liver Protection, we analyzed hepatocyte-specific gp130 knockout mice in a concanavalin A–induced (Con A–induced) model of immune-mediated hepatitis. We demonstrated that IL-6–gp130–dependent pathways in hepatocytes alone are sufficient for triggering Protection in Con A–induced hepatitis. gp130-STAT3 signaling in hepatocytes mediates the IL-6–triggered protective effect. This was demonstrated by analysis of IL-6–induced Protection in mice selectively deficient for gp130-dependent STAT1/3 or gp130-SHP2-RAS signaling in hepatocytes. To identify IL-6–gp130–STAT1/3 dependently expressed Liver-protective factors, we performed gene array analysis of hepatic gene expression in hepatocyte-specific gp130–/– mice as well as in gp130-STAT1/3– and gp130-SHP2-RAS-MAPK–deficient mice. The mouse IL-8 ortholog KC (also known as Gro-α) and serum amyloid A2 (SAA2) was identified as differentially IL-6–gp130–STAT3–regulated genes. Hepatic expression of KC and SAA2 mediate the Liver-protective potential of IL-6, since treatment with recombinant KC or serum SAA2 effectively reduced Liver injury during Con A–induced hepatitis. In summary, this study defines IL-6–gp130–STAT3–dependent gene expression in hepatocytes that mediates IL-6–triggered Protection in immune-mediated Con A–induced hepatitis. Additionally, we identified the IL-6–gp130–STAT3–dependent proteins KC and SAA2 as new candidates for therapeutic targets in Liver diseases.

Christian Klein - One of the best experts on this subject based on the ideXlab platform.

  • the il 6 gp130 stat3 pathway in hepatocytes triggers Liver Protection in t cell mediated Liver injury
    Journal of Clinical Investigation, 2005
    Co-Authors: Christian Klein, Torsten Wustefeld, Ulrike Assmus, Tania Roskams, Stefan Rosejohn, Michael Muller, Michael P Manns, Mattias Ernst, C Trautwein
    Abstract:

    Increasing evidence demonstrates that IL-6 has a protective role during Liver injury. IL-6 activates intracellular pathways via the gp130 receptor. In order to identify IL-6–gp130 pathways involved in mediating Liver Protection, we analyzed hepatocyte-specific gp130 knockout mice in a concanavalin A–induced (Con A–induced) model of immune-mediated hepatitis. We demonstrated that IL-6–gp130–dependent pathways in hepatocytes alone are sufficient for triggering Protection in Con A–induced hepatitis. gp130-STAT3 signaling in hepatocytes mediates the IL-6–triggered protective effect. This was demonstrated by analysis of IL-6–induced Protection in mice selectively deficient for gp130-dependent STAT1/3 or gp130-SHP2-RAS signaling in hepatocytes. To identify IL-6–gp130–STAT1/3 dependently expressed Liver-protective factors, we performed gene array analysis of hepatic gene expression in hepatocyte-specific gp130–/– mice as well as in gp130-STAT1/3– and gp130-SHP2-RAS-MAPK–deficient mice. The mouse IL-8 ortholog KC (also known as Gro-α) and serum amyloid A2 (SAA2) was identified as differentially IL-6–gp130–STAT3–regulated genes. Hepatic expression of KC and SAA2 mediate the Liver-protective potential of IL-6, since treatment with recombinant KC or serum SAA2 effectively reduced Liver injury during Con A–induced hepatitis. In summary, this study defines IL-6–gp130–STAT3–dependent gene expression in hepatocytes that mediates IL-6–triggered Protection in immune-mediated Con A–induced hepatitis. Additionally, we identified the IL-6–gp130–STAT3–dependent proteins KC and SAA2 as new candidates for therapeutic targets in Liver diseases.

  • The IL-6–gp130–STAT3 pathway in hepatocytes triggers Liver Protection in T cell–mediated Liver injury
    Journal of Clinical Investigation, 2005
    Co-Authors: Christian Klein, Stefan Rose-john, Torsten Wustefeld, Ulrike Assmus, Tania Roskams, Michael Muller, Michael P Manns, Mattias Ernst, Christian Trautwein
    Abstract:

    Increasing evidence demonstrates that IL-6 has a protective role during Liver injury. IL-6 activates intracellular pathways via the gp130 receptor. In order to identify IL-6–gp130 pathways involved in mediating Liver Protection, we analyzed hepatocyte-specific gp130 knockout mice in a concanavalin A–induced (Con A–induced) model of immune-mediated hepatitis. We demonstrated that IL-6–gp130–dependent pathways in hepatocytes alone are sufficient for triggering Protection in Con A–induced hepatitis. gp130-STAT3 signaling in hepatocytes mediates the IL-6–triggered protective effect. This was demonstrated by analysis of IL-6–induced Protection in mice selectively deficient for gp130-dependent STAT1/3 or gp130-SHP2-RAS signaling in hepatocytes. To identify IL-6–gp130–STAT1/3 dependently expressed Liver-protective factors, we performed gene array analysis of hepatic gene expression in hepatocyte-specific gp130–/– mice as well as in gp130-STAT1/3– and gp130-SHP2-RAS-MAPK–deficient mice. The mouse IL-8 ortholog KC (also known as Gro-α) and serum amyloid A2 (SAA2) was identified as differentially IL-6–gp130–STAT3–regulated genes. Hepatic expression of KC and SAA2 mediate the Liver-protective potential of IL-6, since treatment with recombinant KC or serum SAA2 effectively reduced Liver injury during Con A–induced hepatitis. In summary, this study defines IL-6–gp130–STAT3–dependent gene expression in hepatocytes that mediates IL-6–triggered Protection in immune-mediated Con A–induced hepatitis. Additionally, we identified the IL-6–gp130–STAT3–dependent proteins KC and SAA2 as new candidates for therapeutic targets in Liver diseases.

  • 90 Hepatocyte GP130/STAT activation results in Liver Protection in immune medi-ated hepatitis
    Journal of Hepatology, 2004
    Co-Authors: Christian Klein, Torsten Wuestefeld, M. Myiazaki, Stefan Rose-john, M. P. Manns, Christian Trautwein
    Abstract:

    tal HCCs (Hepa 1-6 cells in C57L/J mice). However, tumor vaccination strategies might be limited by low levels of tumor infiltration by effector Tlymphocytes. In the present study we therefore analyzed, if intatumoral cytokine/chemokine expression may enhance the efficiency of mAFP-specific DNA-vaccination in a highly aggressive primary murine HCC model. Materials and Methods: Subcutaneous HCC tumors expressing AFP (BW7756) were generated in C57L/J mice by transplantation of tumor pieces. DNA-vaccination was performed at days 4 and 18 by intramuscular injection of expression vectors encoding mAFP, mIL-12 and mGM-CSF. 9 days after DNA-vaccination tumors were injected with adenoviral vectors expressing mIL-12 (Ad-IL-12) and IP-10 (Ad IP-10) or b-galactosidase (Ad-b-gal) as control. Results and Discussion: DNA-vaccination alone, tumor injections with Ad-b-gal and the combination of DNA-vaccination with Ad-b-gal did not show therapeutic efficiency in mice bearing aggressive BW7756 HCCs. Intratumoral adenoviral mIL-12+IP-10 expression resulted in partial tumor regressions, but did not significantly improve animal survival. In contrast, combination of AFP-specific DNA-vaccination with intratumoral Ad-IL12 and Ad IP-10 injection resulted in tumor regressions in all treated animals and prolonged animal survival. These results demonstrate for the first time, that combination of DNA-vaccination with intratumoral gene therapeutic expression of cytokines and chemokines results in improved therapeutic efficiency. This synergistic effect might be caused by enhanced infiltration of the tumor tissue with effector lymphocytes generated by the DNA-vaccination. 90 HEPATOCYTE GP130/STAT ACTIVATION RESULTS IN Liver Protection IN IMMUNE MEDI-ATED HEPATITIS

Wylly Ramses Garcianino - One of the best experts on this subject based on the ideXlab platform.

  • ellagic acid pharmacological activities and molecular mechanisms involved in Liver Protection
    Pharmacological Research, 2015
    Co-Authors: Wylly Ramses Garcianino, Cecilia Zazueta
    Abstract:

    Abstract Traditional drugs or therapies rarely have effects on regression of chronic Liver diseases, which result in many cases from sustained oxidative stress. In recent years, ellagic acid (EA) has gained attention due to its multiple biological activities and several molecular targets. This is the first review focused on the pharmacological properties and on the molecular mechanisms activated by EA in terms of Liver Protection. EA possesses antioxidant, antihepatotoxic, antisteatosic, anticholestatic, antifibrogenic, antihepatocarcinogenic and antiviral properties that improves the hepatic architectural and functions against toxic and pathological conditions. The molecular mechanisms that EA activates include the scavenging of free radicals, regulation of phase I and II enzymes, modulation of proinflammatory and profibrotic cytokines synthesis, the regulation of biochemical pathways involved in the synthesis and degradation of lipids as well as the maintenance of essential trace elements levels. EA also inhibits hepatic stellate cells and mast cells activation, the proliferation of transformed cells, as well as viral replication by increasing antioxidant response, induction of apoptosis, downregulation of genes involved in cell cycle and angiogenesis, and stimulation of cellular immune response. Despite the enormous therapeutic potential of EA as an innovative pharmacological strategy, the number of phase I and II trials in patients is scarce, precluding its clinical application. In these sense, the use of new deLivery systems that enhances EA bioavailability would improve the results already obtained. Also it remains to be determined if treatment with urolithins instead of EA would represent a better strategy in hepatic disease treatment.

Torsten Wustefeld - One of the best experts on this subject based on the ideXlab platform.

  • the il 6 gp130 stat3 pathway in hepatocytes triggers Liver Protection in t cell mediated Liver injury
    Journal of Clinical Investigation, 2005
    Co-Authors: Christian Klein, Torsten Wustefeld, Ulrike Assmus, Tania Roskams, Stefan Rosejohn, Michael Muller, Michael P Manns, Mattias Ernst, C Trautwein
    Abstract:

    Increasing evidence demonstrates that IL-6 has a protective role during Liver injury. IL-6 activates intracellular pathways via the gp130 receptor. In order to identify IL-6–gp130 pathways involved in mediating Liver Protection, we analyzed hepatocyte-specific gp130 knockout mice in a concanavalin A–induced (Con A–induced) model of immune-mediated hepatitis. We demonstrated that IL-6–gp130–dependent pathways in hepatocytes alone are sufficient for triggering Protection in Con A–induced hepatitis. gp130-STAT3 signaling in hepatocytes mediates the IL-6–triggered protective effect. This was demonstrated by analysis of IL-6–induced Protection in mice selectively deficient for gp130-dependent STAT1/3 or gp130-SHP2-RAS signaling in hepatocytes. To identify IL-6–gp130–STAT1/3 dependently expressed Liver-protective factors, we performed gene array analysis of hepatic gene expression in hepatocyte-specific gp130–/– mice as well as in gp130-STAT1/3– and gp130-SHP2-RAS-MAPK–deficient mice. The mouse IL-8 ortholog KC (also known as Gro-α) and serum amyloid A2 (SAA2) was identified as differentially IL-6–gp130–STAT3–regulated genes. Hepatic expression of KC and SAA2 mediate the Liver-protective potential of IL-6, since treatment with recombinant KC or serum SAA2 effectively reduced Liver injury during Con A–induced hepatitis. In summary, this study defines IL-6–gp130–STAT3–dependent gene expression in hepatocytes that mediates IL-6–triggered Protection in immune-mediated Con A–induced hepatitis. Additionally, we identified the IL-6–gp130–STAT3–dependent proteins KC and SAA2 as new candidates for therapeutic targets in Liver diseases.

  • The IL-6–gp130–STAT3 pathway in hepatocytes triggers Liver Protection in T cell–mediated Liver injury
    Journal of Clinical Investigation, 2005
    Co-Authors: Christian Klein, Stefan Rose-john, Torsten Wustefeld, Ulrike Assmus, Tania Roskams, Michael Muller, Michael P Manns, Mattias Ernst, Christian Trautwein
    Abstract:

    Increasing evidence demonstrates that IL-6 has a protective role during Liver injury. IL-6 activates intracellular pathways via the gp130 receptor. In order to identify IL-6–gp130 pathways involved in mediating Liver Protection, we analyzed hepatocyte-specific gp130 knockout mice in a concanavalin A–induced (Con A–induced) model of immune-mediated hepatitis. We demonstrated that IL-6–gp130–dependent pathways in hepatocytes alone are sufficient for triggering Protection in Con A–induced hepatitis. gp130-STAT3 signaling in hepatocytes mediates the IL-6–triggered protective effect. This was demonstrated by analysis of IL-6–induced Protection in mice selectively deficient for gp130-dependent STAT1/3 or gp130-SHP2-RAS signaling in hepatocytes. To identify IL-6–gp130–STAT1/3 dependently expressed Liver-protective factors, we performed gene array analysis of hepatic gene expression in hepatocyte-specific gp130–/– mice as well as in gp130-STAT1/3– and gp130-SHP2-RAS-MAPK–deficient mice. The mouse IL-8 ortholog KC (also known as Gro-α) and serum amyloid A2 (SAA2) was identified as differentially IL-6–gp130–STAT3–regulated genes. Hepatic expression of KC and SAA2 mediate the Liver-protective potential of IL-6, since treatment with recombinant KC or serum SAA2 effectively reduced Liver injury during Con A–induced hepatitis. In summary, this study defines IL-6–gp130–STAT3–dependent gene expression in hepatocytes that mediates IL-6–triggered Protection in immune-mediated Con A–induced hepatitis. Additionally, we identified the IL-6–gp130–STAT3–dependent proteins KC and SAA2 as new candidates for therapeutic targets in Liver diseases.