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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

A FAS approach for stabilization of generalized chained forms: part 1. Discontinuous control laws

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Science China(Information Sciences) 2024年第2期67卷 118-143页

作者： Guang-ren DUAN Center for Control Theory and Guidance Technology Harbin Institute of Technology Center for Control Science and Technology Southern University of Science and Technology

In this paper, a type of general nonholonomic systems is proposed, which contains both the Brockett’s two example systems, and their extended n-dimensional chained forms, as special cases. For the stabilization of such systems, a stabilizing controller is proposed based on the fully actuated system(FAS)approach, which is discontinuous at the origin but time-invariant when the open-loop system is time-invariant,and drives the feasible trajectories of the system to the origin exponentially. Furthermore, the proposed FAS approach is also extended to the sub-normal system case and the time-delay system case.

关键词： nonholonomic systems feedback stabilization exponential convergence sub-fully actuated systems time-delay systems

A FAS approach for stabilization of generalized chained forms: part 2. Continuous control laws

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Science China(Information Sciences) 2024年第3期67卷 114-135页

作者： Guang-ren DUAN Center for Control Theory and Guidance Technology Harbin Institute of Technology Shenzhen Key Laboratory of Control Theory and Intelligent Systems Southern University of Science and Technology

In this paper, continuous time-varying stabilizing controllers for the type of general nonholonomic systems proposed and treated in part 1 are designed using the fully actuated system(FAS) approach. The key step is to differentiate the first scalar equation, and by control of the obtained second-order scalar system, a proportional plus integral feedback form for the first control variable is obtained. With the solution to this designed second-order scalar system, the rest equations in the nonholonomic system form an independent time-varying subsystem which is then handled by the FAS approach. The overall designed controller contains an almost arbitrarily chosen design parameter, and is proven to guarantee the uniformly and globally exponential stability of the closed-loop system. The proposed approach is simple and effective,and is demonstrated with a practical example of ship control.

关键词： nonholonomic systems feedback stabilization fully actuated systems Lyapunov stability continuous controllers

Impact of body mass index on hepatocellular carcinoma recurrence after liver transplantation through long-term follow-up

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 598-609页

作者： Nada El-Domiaty Faouzi Saliba Vincent Karam Rodolphe Sobesky Wafaa Ibrahim Eric Vibert Gabriella Pittau Khaled Amer Maysaa ASaeed Jihan AShawky Daniel Cherqui renéadam Didier Samuel AP-HP Hôpital Paul Brousse Hepato-Biliary CentreINSERM UMR 1193UniversitéParis SaclayVillejuifFrance Tropical Medicine Department Faculty of MedicineZagazig UniversityZagazigEgypt Statistics Department Faculty of Economics and Political ScienceCairo UniversityCairoEgypt Hepato-Biliary and Liver Transplant Department International Medical CenterCairoEgypt

Background:Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index(BMI)on increased risk of hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)is still *** purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and ***:Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were *** were classified at time of LT according to the World Health Organization BMI classification into 3 groups;group 1:BMIrence rates of HCC after LT in the three groups were 19%,16%and 17%*** 5,10 and 15-year recurrence free survival(RFS)rates were respectively 68.6%,47.3%and 40.8%in group 1,73.3%,66.2%and 49.5%in group 2 and 68.8%,57.5%and 47.7%in group 3(log rank P=0.47).Conclusions:Recipient BMI at time of transplant and during follow-up didn’t impact the incidence of HCC recurrence nor long-term patient survival,irrespective to the status of the patients and their tumor characteristic at time of *** present study clearly confirms that obesity should not be considered,when selecting patients with HCC to LT,as a predictive factor of recurrence.

关键词： Hepatocellular carcinoma(HCC) obesity body mass index(BMI) nutrition liver transplantation(LT) hepatocellular carcinoma recurrence(HCC recurrence)

Resilient control of flexible hypersonic vehicles against unmatched distributed faults

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Chinese Journal of Aeronautics 2024年第5期37卷 60-70页

作者： Dong ZHAO Wenjing ren School of Artificial Intelligence Anhui UniversityHefei 230601China Key Laboratory of System Control and Information Processing Ministry of EducationShanghai Jiao Tong UniversityShanghai 200240China School of Electrical Engineering and Automation Hefei University of TechnologyHefei 230009China

This paper studies a robust fault compensation and vibration suppression problem of flexible hypersonic *** controlled plant is represented by a cascade system composed of a nonlinear Ordinary Differential Equation(ODE)and an Euler-Bernoulli Beam Equation(EBBE),in which the vibration dynamics is coupled with the rigid dynamics and suffers from distributed faults.A state differential transformation is introduced to transfer distributed faults to an EBBE boundary and a longitudinal dynamics is refined by utilizing T-S fuzzy IF-THEN rules.A novel T-S fuzzy based fault-tolerant control algorithm is developed and related stability conditions are *** robust exponential stability and well-posedness are proved by using the modified l_(0)-semigroup based Lyapunov direct approach.A simulation study on the longitudinal dynamics of flexible hypersonic vehicles effectively verifies the validity of the developed theoretical results.

关键词： Flexible hypersonic vehicles ODE-EBBE cascade Robust exponential stability Unmatched distributed fault compensation Vibration suppression