The Experts below are selected from a list of 14106 Experts worldwide ranked by ideXlab platform
Yuan Zhai - One of the best experts on this subject based on the ideXlab platform.
-
the dichotomy of endoplasmic reticulum stress response in Liver Ischemia reperfusion injury
Transplantation, 2016Co-Authors: Haomming Zhou, Ronald W. Busuttil, Jerzy W Kupiecweglinski, Jianjun Zhu, Shi Yue, X Wang, Yuan ZhaiAbstract:Endoplasmic reticulum (ER) stress plays critical roles in the pathogenesis of Liver Ischemia-reperfusion injury (IRI). As ER stress triggers an adaptive cellular response, the question of what determines its functional outcome in Liver IRI remains to be defined. In a murine Liver partial warm Ischemia model, we studied how transient (30 minutes) or prolonged (90 minutes) Liver Ischemia regulated local ER stress response and autophagy activities and their relationship with Liver IRI. Effects of chemical chaperon 4-phenylbutyrate (4-PBA) or autophagy inhibitor 3-methyladenine (3-MA) were evaluated. Our results showed that although the activating transcription factor 6 branch of ER stress response was induced in Livers by both types of Ischemia, Liver autophagy was activated by transient, but inhibited by prolonged, Ischemia. Although 3-MA had no effects on Liver IRI after prolonged Ischemia, it significantly increased Liver IRI after transient Ischemia. The 4-PBA treatment protected Livers from IRI after prolonged Ischemia by restoring autophagy flux, and the adjunctive 3-MA treatment abrogated its Liver protective effect. The same 4-PBA treatment, however, increased Liver IRI and disrupted autophagy flux after transient Ischemia. Although both types of Ischemia activated 5' adenosine monophosphate-activated protein kinase and inactivated protein kinase B (Akt), prolonged Ischemia also resulted in downregulations of autophagy-related gene 3 and autophagy-related gene 5 in ischemic Livers. These results indicate a functional dichotomy of ER stress response in Liver IRI via its regulation of autophagy. Transient Ischemia activates autophagy to protect Livers from IRI, whereas prolonged Ischemia inhibits autophagy to promote the development of Liver IRI.
-
Innate Immune Regulations and Liver Ischemia-Reperfusion Injury.
Transplantation, 2016Co-Authors: Haoming Zhou, Xuehao Wang, Ronald W. Busuttil, Jerzy W. Kupiec-weglinski, Yuan ZhaiAbstract:Liver Ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations. Additionally, tissue injury milieu activates PRR-independent receptors which also regulate inflammatory disease processes. Thus, the innate immune mechanism of Liver Ischemia-reperfusion injury involves diverse molecular and cellular interactions, subjected to both endogenous and exogenous regulation in different cells. A better understanding of these complicated regulatory pathways/network is imperative for us in designing safe and effective therapeutic strategy to ameliorate Liver Ischemia-reperfusion injury in patients.
Luis H. Toledo-pereyra - One of the best experts on this subject based on the ideXlab platform.
-
Selectins in Liver Ischemia and Reperfusion Injury
Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2015Co-Authors: Ryan T. Jones, Luis H. Toledo-pereyra, Kelly QuesnelleAbstract:Liver Ischemia reperfusion injury is mediated by a complex system of signaling cascades and inflammatory response resulting in organ damage. Selectins are a group of cell adhesion glycoproteins that play a key role in the initial immunological response. L-selectins, found on leukocytes, initiate the original adhesion and rolling phase of leukocyte extravasation upon Liver sinusoidal endothelial cells (LSECs). P-selectins, found on platelets and tissue-specific endothelial cells, further increases leukocyte-endothelial adhesion and rolling. P-selectin-ligand binding also initiates intracellular signals that produce adhesion molecules to start firm adhesion and increase local chemokine production. L-selectin-ligand binding on the leukocytes increases adhesion molecule expression and chemokines, but also initiate changes in intracellular structural actin. E-selectin expression occurs with the presence of TNF-α and/or IL-1β. E-selectin-ligand binding decreases leukocyte rolling velocity and increases adhesion molecules. Together, these glycoproteins transition the leukocyte response from original margination and rolling to firm adhesion and eventually migration.
-
Pentoxifylline in Liver Ischemia and Reperfusion
Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2013Co-Authors: Patricia Genovés, David Garcia, Dolores Cejalvo, Antonio Martin, C. Zaragoza, Alexander H. Toledo, Luis H. Toledo-pereyra, José Miguel Lloris-carsíAbstract:Pentoxifylline is a methylxanthine compound which was first filed in 1973 and registered in 1974 in the United States by Sanofi-Aventis Deustchland Gmbh for the treatment of intermittent claudication for chronic occlusive arterial disease. This methylxanthine was later discovered to be a phosphodiesterase inhibitor. Furthermore, its hemorheological properties and its function as an inhibitor of inflammatory cytokines, like TNF- α, allowed researchers to study its effects in organ Ischemia and reperfusion and transplantation. Although this drug has demonstrated beneficial effects, the mechanisms by which Pentoxifylline exerts a protective effect are not fully understood. This paper focuses on reviewing the literature to define the effect of Pentoxifylline when used in Liver Ischemia and reperfusion injury. Our research shows different animal models in which Pentoxifylline has been used as well as different doses and time of administration, as the ideal dose and timing have not yet been ascertained in Liver Ischemia and reperfusion. In conclusion, Pentoxifylline has shown positive effects in Liver Ischemia and reperfusion injury, and the main mechanism seems to be associated with the inhibition of TNF-α.
-
Allopurinol and xanthine oxidase inhibition in Liver Ischemia reperfusion
Journal of Hepato-Biliary-Pancreatic Sciences, 2011Co-Authors: Stephanie Peglow, Alexander H. Toledo, Roberto Anaya-prado, Fernando Lopez-neblina, Luis H. Toledo-pereyraAbstract:Introduction Allopurinol was first introduced, in 1963, as a xanthine oxidase inhibitor when it was investigated for concomitant use with cancer chemotherapy drugs. Today it is used in gout and hyperuricemia. Due to its additive benefit in preventing oxidative damage, attention has shifted towards the use of allopurinol in organ Ischemia and reperfusion. Current status Currently, the mechanism by which allopurinol exerts a protective benefit in Ischemia reperfusion related events is not fully understood. There are various theories: it may act by inhibiting the irreversible breakdown of purine substrates, and/or by inhibiting the formation of reactive oxygen species, and/or by protecting against damage to the mitochondrial membrane. Aim This work focuses on Liver Ischemia and reperfusion injury in an effort to better understand the mechanisms associated with allopurinol and with this pathological entity. Review of literature The current research, mainly in animal models, points to allopurinol having a protective benefit, particularly if used pre-ischemically in Liver Ischemia reperfusion injury. Furthermore, after reviewing allopurinol dosing and administration, it was found that 50 mg/kg is statistically the most effective dose in attenuating Liver Ischemia reperfusion injury. Owing to the limited number of samples, the time of administration did not show statistical difference, but allopurinol was often beneficial when given around 1 h before Ischemia. Conclusion In conclusion, allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the Liver during Ischemia and reperfusion.
-
Role of p38 and JNK in Liver Ischemia and reperfusion
Journal of hepato-biliary-pancreatic surgery, 2009Co-Authors: Lashonda A. King, Alexander H. Toledo, Fernando A. Rivera-chavez, Luis H. Toledo-pereyraAbstract:Background/purpose The signal transduction of mitogen-activated protein kinases (MAPKs) has appeared to be an important mediator of ischemic-related events. Because of this, we analyzed the participation of p38 and JNK in Liver Ischemia and reperfusion, as two individual members of the MAPK family of proteins.
-
Inflammatory mediators of Liver Ischemia-reperfusion injury.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2009Co-Authors: Kyle B. Walsh, Alexander H. Toledo, Fernando Lopez-neblina, Fernando A. Rivera-chavez, Luis H. Toledo-pereyraAbstract:Liver Ischemia and reperfusion--which cause Liver damage that is significant in a variety of diseases, injuries, and procedures (including but not limited to trauma and transplant)--have been the focus of many investigations in recent years. Although the mechanisms of Ischemia-reperfusion injury are numerous and complex, many advances in treatment have been made. The following review considers recent advances in the understanding of hepatic Ischemia-reperfusion injury and focuses on inflammatory mediators of significance. To provide a unique analysis and evaluation, we emphasized the most recent pertinent investigations of the last decade. Specific topics addressed include reactive oxygen species, nitric oxide, toll-like receptors, ischemic preconditioning, T cells, heme oxygenase-1, heat shock proteins, erythropoietin, selectins, protein kinases, matrix metalloproteinases, and cytokines.
Marcel Cerqueira Cesar Machado - One of the best experts on this subject based on the ideXlab platform.
-
timing dependent protection of hypertonic saline solution administration in experimental Liver Ischemia reperfusion injury
Surgery, 2010Co-Authors: Estela Regina Ramos Figueira, Telesforo Bacchella, Ana Maria M Coelho, Sandra N Sampietre, Nilza A T Molan, Regina Maria Cubero Leitao, Marcel Cerqueira Cesar MachadoAbstract:Background During Liver Ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during Liver transplantation, Liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental Liver Ischemia/reperfusion. Methods Rats underwent 1 hr of warm Liver Ischemia followed by reperfusion. Eighty-four rats were allocated into 6 groups: sham group, control of Ischemia group (C), pre-Ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-reperfusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion. Results HTS showed beneficial effects in prevention of Liver Ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-Ischemia group. No differences in IL-6 and IL-10 levels were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The Liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-Ischemia HTS group. Conclusion HTS ameliorated local and systemic injuries in experimental Liver Ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results.
-
Timing-dependent protection of hypertonic saline solution administration in experimental Liver Ischemia/reperfusion injury
Surgery, 2009Co-Authors: Estela Regina Ramos Figueira, Telesforo Bacchella, Ana Maria M Coelho, Sandra N Sampietre, Nilza A T Molan, Regina Maria Cubero Leitao, Marcel Cerqueira Cesar MachadoAbstract:Background During Liver Ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during Liver transplantation, Liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental Liver Ischemia/reperfusion. Methods Rats underwent 1 hr of warm Liver Ischemia followed by reperfusion. Eighty-four rats were allocated into 6 groups: sham group, control of Ischemia group (C), pre-Ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-reperfusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion. Results HTS showed beneficial effects in prevention of Liver Ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-Ischemia group. No differences in IL-6 and IL-10 levels were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The Liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-Ischemia HTS group. Conclusion HTS ameliorated local and systemic injuries in experimental Liver Ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results.
-
Rosiglitazone-enriched diet did not protect Liver Ischemia-reperfusion injury in a rat model
Acta cirurgica brasileira, 2008Co-Authors: Antonio Roberto Franchi Teixeira, Telesforo Bacchella, Ana Maria M Coelho, Nilza A T Molan, Marta Bellodi-privato, Katia R. M. Leite, Antonio Carlos Seguro, Marcel Cerqueira Cesar MachadoAbstract:PURPOSE: To determine whether rosiglitazone-enriched diet offer protection in a classical model of Liver Ischemia-reperfusion injury in rats. METHODS: Two days before the experiment, rats were divided into 2 groups: Control Group (n=13) rats fed with standard diet; Rosi Group (n=13): rats fed with a powdered standard diet supplemented with rosiglitazone. The animals were submitted to Liver Ischemia-reperfusion by clamping the pedicle of median and left anterolateral lobes. After 1 hour of partial hepatic Ischemia, the clamp was removed for reperfusion. After 2 or 24 hours (Control and Rosi Groups), blood was collected for enzymes and cytokines analysis. Ischemic and non-ischemic Liver were collected for malondialdehyde analysis and histological assessment. Lungs were removed for tissue myeloperoxidase quantification. RESULTS: There were no statistical differences between groups for all analysed parameters. CONCLUSION: In this model, rosiglitazone-enriched diet did not protect Liver against Ischemia-reperfusion injury.
Lianbao Kong - One of the best experts on this subject based on the ideXlab platform.
-
miR-146a ameliorates Liver Ischemia/reperfusion injury by suppressing IRAK1 and TRAF6.
PloS one, 2014Co-Authors: Weiwei Jiang, Liang-liang Kong, Wen-zhou Ding, Guo-qing Liu, Weibing Tang, Lianbao KongAbstract:A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor– associated factor 6(TRAF6), in the pathogenesis of Liver Ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and Liver I/R injury in vivo and in vitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a in vivo, protected against Liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates Liver Ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6.
-
mir 146a ameliorates Liver Ischemia reperfusion injury by suppressing irak1 and traf6
PLOS ONE, 2014Co-Authors: Weiwei Jiang, Liang-liang Kong, Wen-zhou Ding, Guo-qing Liu, Weibing Tang, Lianbao KongAbstract:A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor– associated factor 6(TRAF6), in the pathogenesis of Liver Ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and Liver I/R injury in vivo and in vitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a in vivo, protected against Liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates Liver Ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6.
X Wang - One of the best experts on this subject based on the ideXlab platform.
-
the dichotomy of endoplasmic reticulum stress response in Liver Ischemia reperfusion injury
Transplantation, 2016Co-Authors: Haomming Zhou, Ronald W. Busuttil, Jerzy W Kupiecweglinski, Jianjun Zhu, Shi Yue, X Wang, Yuan ZhaiAbstract:Endoplasmic reticulum (ER) stress plays critical roles in the pathogenesis of Liver Ischemia-reperfusion injury (IRI). As ER stress triggers an adaptive cellular response, the question of what determines its functional outcome in Liver IRI remains to be defined. In a murine Liver partial warm Ischemia model, we studied how transient (30 minutes) or prolonged (90 minutes) Liver Ischemia regulated local ER stress response and autophagy activities and their relationship with Liver IRI. Effects of chemical chaperon 4-phenylbutyrate (4-PBA) or autophagy inhibitor 3-methyladenine (3-MA) were evaluated. Our results showed that although the activating transcription factor 6 branch of ER stress response was induced in Livers by both types of Ischemia, Liver autophagy was activated by transient, but inhibited by prolonged, Ischemia. Although 3-MA had no effects on Liver IRI after prolonged Ischemia, it significantly increased Liver IRI after transient Ischemia. The 4-PBA treatment protected Livers from IRI after prolonged Ischemia by restoring autophagy flux, and the adjunctive 3-MA treatment abrogated its Liver protective effect. The same 4-PBA treatment, however, increased Liver IRI and disrupted autophagy flux after transient Ischemia. Although both types of Ischemia activated 5' adenosine monophosphate-activated protein kinase and inactivated protein kinase B (Akt), prolonged Ischemia also resulted in downregulations of autophagy-related gene 3 and autophagy-related gene 5 in ischemic Livers. These results indicate a functional dichotomy of ER stress response in Liver IRI via its regulation of autophagy. Transient Ischemia activates autophagy to protect Livers from IRI, whereas prolonged Ischemia inhibits autophagy to promote the development of Liver IRI.
-
remote ischemic preconditioning protects against Liver Ischemia reperfusion injury via heme oxygenase 1 induced autophagy
PLOS ONE, 2014Co-Authors: Yun Wang, Jian Shen, Xuanxuan Xiong, Hai Zhang, Changjun Huang, Yuan Tian, Chengyu Jiao, X WangAbstract:Background Growing evidence has linked autophagy to a protective role of preconditioning in Liver Ischemia/reperfusion (IR). Heme oxygenase-1 (HO-1) is essential in limiting inflammation and preventing the apoptotic response to IR. We previously demonstrated that HO-1 is up-regulated in Liver graft after remote ischemic preconditioning (RIPC). The aim of this study was to confirm that RIPC protects against IR via HO-1-mediated autophagy.