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Peroxisome proliferator-activated receptor γ agonist reduces the severity of post-ERCP pancreatitis in rats

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World Journal of Gastroenterology 2006年第40期12卷 6458-6463页

作者： Emma folch-Puy Susana Granell Juan L Iovanna Marc Barthet Daniel Closa Department of Experimental Pathology IIBB-CSIC IDIBAPS Barcelona Spain INSERM U.624 Stress Cellulaire Marseille France

AIM： To determine the effects of prophylactic peroxisome proliferator-activated receptor （PPARy） agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography （post-ERCP） acute pancreatitis. METHODS： Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS： Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity （MPO） in pancreas. This result correlated with the activation of nuclear factor κB （NFκB） and the inducible NO synthase （iNOS） expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression. CONCLUSION： A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.

关键词： Peroxisome proliferator-activated receptor γ Pancreatitis Endoscopic retrograde cholangio pancreatography Inflammation Nuclear factor κB

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

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World Journal of Gastroenterology 2020年第39期26卷 5970-5982页

作者： Ana Ferrero-Andrés Arnau Panisello-Roselló Joan Roselló-Catafau Emma folch-Puy Experimental Pathology Department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasBarcelona 08036CataloniaSpain Experimental Pathology Department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasInstitut d'Investigacions Biomèdiques August Pi i SunyerBarcelona 08036CataloniaSpain

BACKGROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote *** and parenchymal cell death are common pathological features of this condition and determinants of disease *** glycols(PEGs)are nonimmunogenic,non-toxic water-soluble polymers widely used in biological,chemical,clinical and pharmaceutical *** To evaluate the protective effect of a 35-kDa molecular weight PEG(PEG35)on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in *** Wistar rats were assigned at random to a control group,a cerulein–induced AP group and a PEG35 treatment *** was induced by five hourly intraperitoneal injections of cerulein(50μg/kg/bw),while the control animals received saline ***35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/*** AP induction,samples of pancreatic tissue and blood were collected for ***42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factorα(TNFα),staurosporine or *** severity of AP was determined on the basis of plasma levels of lipase,lactate dehydrogenase activity,pancreatic edema and histological *** evaluate the extent of the inflammatory response,the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated ***-induced cell death was also measured in models of in vivo and in vitro pancreatic *** Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP *** increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the *** contr

关键词： Acute pancreatitis Inflammation Polyethylene glycols Cytokines AR42J cells Cell death

Large-scale microfluidic gradient arrays reveal axon guidance behaviors in hippocampal neurons

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Microsystems & Nanoengineering 2017年第1期3卷 302-315页

作者： Nirveek Bhattacharjee alber. folch Department of Bioengineering University of Washington372015th Ave NEFoege N423-ASeattleWA 98195USA

High-throughput quantitative approaches to study axon growth behaviors have remained a *** have developed a 1024-chamber microfluidic gradient generator array that enables large-scale investigations of axon guidance and growth dynamics from individual primary mammalian neurons,which are exposed to gradients of diffusible *** microfluidic method(a)generates statistically rich data sets,(b)produces a stable,reproducible gradient with negligible shear stresses on the culture surface,(c)is amenable to the long-term culture of primary neurons without any unconventional protocol,and(d)eliminates the confounding influence of cell-secreted *** this platform,we demonstrate that hippocampal axon guidance in response to a netrin-1 gradient is concentration-dependent—attractive at higher concentrations and repulsive at lower *** also show that the turning of the growth cone depends on the angle of incidence of the *** study highlights the potential of microfluidic devices in producing large amounts of data from morphogen and chemokine gradients that play essential roles not only in axonal navigation but also in stem cell differentiation,cell migration,and immune response.

关键词： axon guidance microfluidic gradient microjet netrin-1 primary mammalian neuron

Emerging concepts in liver graft preservation

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世界胃肠病学杂志：英文版 2015年第2期21卷 396-407页

作者： Mohamed Bejaoui Eirini Pantazi Emma folch-Puy Pedro M Baptista Agustín García-Gil René Adam Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institute of Biomedical Research of Barcelona-Spanish National Research CouncilCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas08036 BarcelonaCataloniaSpain Universidad de Zaragoza CIBER- ehdAragon Health Sciences Institute50009 ZaragozaSpain AP-HP H?pital Paul Brousse Centre Hépato-BiliaireUniversité Paris-Sud Villejuif75008 ParisFrance

The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion(MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures(hypothermia at 4 ℃, normothermia a t 3 7 ℃ and subnormothermia at 20 ℃- 2 5 ℃). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the "state of the art" and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.

关键词： Static cold preservation Suboptimal liver grafts P

Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury:An update

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World Journal of Gastroenterology 2018年第27期24卷 2984-2994页

作者： Arnau Panisello-Roselló Alexandre Lopez Emma folch-Puy Teresa Carbonell Anabela Rolo Carlos Palmeira René Adam Marc Net Joan Roselló-Catafau Department of Experimental Pathology Institute of Biomedical Research of Barcelona(IIBB)-CSICBarcelona 08036Spain Centre Hepatobiliare AP-HP Hopital Paul BrousseVillejuif 75008France Department of Physiology Faculty of BiologyUniversitat de BarcelonaBarcelona 08036Spain Center for Neuroscience and Cell Biology University of CoimbraCoimbra 3004-517Portugal Institute Georges Lopez Lissieu 69380France

Aldehyde dehydrogenase 2(ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury(IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic "preconditioning" strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation.

关键词： Aldehyde dehydrogenase 2 4-hydroxy-2-nonenal autophagy Apoptosis Ischemia reperfusion injury Preconditioning

Polyethylene glycol rinse solution:An effective way to prevent ischemia-reperfusion injury

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World Journal of Gastroenterology 2014年第43期20卷 16203-16214页

作者： Mohamed Amine Zaouali Mohamed Bejaoui Maria Calvo Emma folch-Puy Eirini Pantazi Gianfranco Pasut Antoni Rimola Hassen Ben Abdennebi René Adam Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit IIBB-CSICCSIC-IDIBAPS08036 BarcelonaSpain Molecular Biology and Anthropology Applied to Development and Health (UR12ES11) Faculty of PharmacyUniversity of Monastir5000 MonastirTunisia Serveis Cientifico-Tècnics Universitat de Barcelona08036 BarcelonaSpain Pharmaceutical and Pharmacological Department University of Padova35122 PadovaItaly Hospital Clínic Networked Biomedical Research Center of Hepatic and Digestive Diseases (Ciber EHD)08036 BarcelonaSpain AP-HP H?pital Paul Brousse Centre Hepato-BiliaireUniv Paris-Sud Villejuif75008 ParisFrance

AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts.

关键词： Liver washout Liver transplantation Rinse solution Ischemia-reperfusion injury Polyethylene glycol 35 Nitric oxide Adenosine monophosphate-activated protein kinase Heme oxygenase 1 Heat shock protein 70 Metalloproteinases

Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第28期22卷 6501-6508页

作者： Gianfranco Pasut Arnau Panisello Emma folch-Puy Alexandre Lopez Carlos Castro-Benítez Maria Calvo Teresa Carbonell Agustín García-Gil RenéAdam Joan Roselló-Catafau Department of Pharmaceutical and Pharmacological University of Padova and Veneto Institute of Oncology IRCCS 35128 Padova Italy Experimental Pathology Department Institute of Biomedical Research of Barcelona 08036 Barcelona Spain Centre Hepatobiliaire AP-HP Hopital Paul Brousse Inserm U935 Universite Paris-Sud Villejuif 75008 Paris France Unitat de Microscopia Optic Avancada CCiTUB Centre Cientifics i Tecnologics Faculty of Medicine University of Barcelona 08036 Barcelona Spain Physiology Department Faculty of Biology Universitat de Barcelona 08036 Barcelona Spain Hospital Clinico de Zaragoza 50009 Zaragoza Spain

Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.

关键词： Ischemia reperfusion injury Polyethylene glycol Liver preconditioning Liver transplantation UW solution IGL-1 solution SCOT solution PEG rinse solution Machine perfusion

Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal

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World Journal of Gastroenterology 2017年第23期23卷 4211-4221页

作者： Mohamed Amine Zaouali Arnau Panisello-Roselló Alexandre Lopez Carlos Castro Benítez Emma folch-Puy Agustín García-Gil Teresa Carbonell RenéAdam Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institut d’Investigacions Biomèdiques de BarcelonaSpanish National Research Council Research Unit of Biology and molecular anthropology applied to development and Health(UR12ES11) Faculty of PharmacyUniversity of Monastir Tunisia and Institute of Biotechnology of Monastir University of Monastir Centre Hépatobiliaire AP-PHHopital Paul Brousse Hospital Clínico de Zaragoza Facultat Biologia Universitat de Barcelona

To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) *** liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to “ex vivo” normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).RESULTSProfiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 *** comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a hig

关键词： Liver proteolysis Proteasome activation Fatty liver preservation Institut Georges Lopez-1 University of Wisconsin High mobility group box 1 Cold ischemia reperfusion injury

Role of sirtuins in ischemia-reperfusion injury

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World Journal of Gastroenterology 2013年第43期19卷 7594-7602页

作者： Eirini Pantazi Mohamed Amine Zaouali Mohamed Bejaoui Emma folch-Puy Hassen Ben Abdennebi Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institut of Biomedical Research of Barcelona-Spanish National Research CouncilBarcelona08036 CataloniaSpain Molecular Biology and Anthropology applied to development and health (UR12ES11) Faculty of PharmacyMonastir 5000Tunisia Experimental Pathology Department Institute of Biomedical Research of Barcelona-Spanish National Research CouncilBarcelona08036 CataloniaSpain

Ischemia-reperfusion injury(IRI)remains an unresolved and complicated situation in clinical practice,especially in the case of organ *** factors contribute to its complexity;the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ ***,the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers,due to their involvement in the modulation of a wide variety of cellular *** are seven mammalian sirtuins and,among them,the nuclear/cytoplasmic sirtuin 1(SIRT1)and the mitochondrial sirtuin 3(SIRT3)are ubiquitously expressed in many tissue *** are known to play major roles in protecting against cellular stress and in controlling metabolic pathways,which are key processes during *** this review,we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress,apoptosis,microcirculatory stress and inflammation during *** present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.

关键词： Sirtuin 1 Sirtuin 3 Ischemia-reperfusion injury oxidative stress Apoptosis