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Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis

World Journal of Gastroenterology 2017年第15期23卷 2673-2684页

作者： Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski nazia selzner Andrzej Chruscinski Gary A Levy Multi Organ Transplant Program University Health Network Department of Laboratory Medicine and Pathology University Health Network Gastroenterology Hepatology and Nutrition DivisionThe Hospital for Sick Children

AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1-/- *** and Teff cells from fgl2-/-, fgl2+/+, and fgl2Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/- *** vitro, fgl2Tg Treg had enhanced immunosuppressive activity, and fgl2Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2+/+) into Rag1-/- mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/- Treg were only partially protective. In mice that received fgl2Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2Tg mice did not produce *** we show that fgl2Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.

关键词： Fibrinogen-like protein 2 Colitis Regulatory T cells Transgenic mouse Inflammatory bowel disease

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Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant:A retrospective cohort study

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World Journal of Gastroenterology 2022年第26期28卷 3218-3231页

作者： Fakhar Ali Qazi-Arisar Raj Uchila Catherine Chen Cathy Yang Shi-Yi Chen Ravikiran Sindhuvalada Karnam Amirhossein Azhie Wei Xu Zita Galvin nazia selzner Leslie Lilly Mamatha Bhat Ajmera Transplant Program Toronto General HospitalUniversity Health NetworkToronto M5G 2N2OntarioCanada Division of Gastroenterology and Hepatology Department of MedicineUniversity of TorontoToronto M5G 2N2OntarioCanada National Institute of Liver and GI Diseases Dow University of Health SciencesKarachi 75330Pakistan Department of Biostatistics Princess Margaret Cancer CenterUniversity Health NetworkToronto M5G 2C1OntarioCanada Division of Biostatistics Dalla Lana School of Public HealthUniversity of TorontoToronto M5G 2C1OntarioCanada

BACKGROUND Non-alcoholic steatohepatitis(NASH)cirrhosis is the second most common indication for liver transplantation(LT).The role of body mass index(BMI)on outcomes of NASH cirrhosis has been *** To compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis,from listing up to post-transplant,having adjusted their BMI for *** We retrospectively reviewed all adult NASH patients listed for LT in our program from 2012 to ***-Gray Competing Risk analyses and Cox Proportional-Hazard Models were performed to examine the cumulative incidence of transplant and survival outcomes *** Out of 265 NASH cirrhosis listed patients,176 were *** age was 61.0 years;46%were females.111 patients underwent *** robust patients had better waitlist survival[hazard ratio(HR):0.12;95%CI:0.05–0.29,P<0.0001]with higher instantaneous rate of transplant(HR:5.71;95%CI:1.26–25.9,P=0.02).Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT(1.2%vs 13.8%,P=0.032)and death post-LT(2.4%vs 17.2%,P=0.029).1-3-and 5-year graft survival was poor for lean NASH(78.6%,77.3%and 41.7%vs 98.6%,96%and 85%respectively).Overall patient survival post-LT was significantly worse in lean NASH(HR:0.17;95%CI:0.03–0.86,P=0.0142)with 83%lower instantaneous rate of death in obese *** Although lean NASH is considered to be more benign than obese NASH,our study suggests a paradoxical correlation of lean NASH with waitlist outcomes,and graft and patient survival post-LT.

关键词： Outcomes Frailty Waitlist Liver transplant Survival

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Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

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World Journal of Translational Medicine 2014年第2期3卷 58-68页

作者： Fateh Bazerbachi nazia selzner John B Seal Markus selzner Department of Medicine University of Minnesota Department of Medicine University of TorontoMultiorgan Transplant Program Toronto General Hospital Department of Surgery University of Toronto Multiorgan Transplant Program Toronto General Hospital

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

关键词： Transplant hepatology Liver transplantation Organ donation Extended criteria donors Donation after cardiac death Ex-vivo liver perfusion Normothermic machine perfusion Hypothermic machine perfusion

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