Most of the SRY-positive cells were observed surrounding the portal area and bile duct

Our findings suggest that hHGF-modified HOC transplantation may provide a valuable approach for the treatment of patients with severe liver damage. Even though liver transplantation is the most efficient means of treating patients with end-stage liver diseases, it is usually associated with postoperative (+)-JQ1 complications, including acute allograft rejection, chronic renal failure, post-transplantation lymphoproliferative disorders, and cardiovascular disease. Among these side-effects, liver allograft rejection is considered to be a severe and major complication associated with significant morbidity and reduced life quality in liver transplant recipients. Furthermore, the use of immunosuppressive agents may also cause a variety of adverse side effects such as inducing diabetes, hypertension, and nephrotoxicity, and therefore needs careful risk assessments before use. Concomitant stem cell transplantation may induce allograft tolerance by modulating immune cell responses. In the present study, administration of HOC following liver transplantation significantly decreased acute liver rejection and prolonged the survival period of recipients. Previous studies revealed that sustained expression of HGF could accelerate the proliferation of HOCs in a rat 2-AAF/PH model, suggesting that modification to the HGF gene may promote in vivo proliferation and differentiation of HOCs, thereby benefitting liver regeneration post transplantation. In this study, a HOC line stably expressing the hHGF gene was successfully established and shown in vitro to efficiently differentiate into large, round hepatocytes or into long spindle-like bile duct epithelial cells consistent with previous reports. Laboratory tests indicated that combined hHGF-HOC transplantation down-regulated ALT, DBil, GGT, ALP levels but upregulated ChE, and ALB expression levels, suggesting that transplantation in combination with the administration of HOCs improved liver function, prevented bile duct damage, and protected against development of chronic hepatocyte injury. Since hHGF-modified HOCs are capable of secreting hHGF, it is possible that secreted hHGF may promote the proliferation, differentiation, and migration of HOCs in injured liver tissues while also enhancing the repair and regeneration of the donor liver.Therefore, it would be reasonable to suggest that these cells contributed to the protection of intrahepatic biliary epithelial cells. The rat acute rejection orthotopic liver transplantation model using DA rat livers transplanted into Lewis rats was used to assess the protective effects of HOC cell administration on acute liver rejection. Without interventions, liver recipients would die of acute rejection, postoperative infections, abdominal bleeding, or respiration and circulation failure within one week post surgery. In this study, liver recipients were treated with tacrolimus 1 day prior to surgery until day 13 post surgery. Animals that died within 7 days post surgery were excluded from subsequent examinations. In the environment vertebrates are constantly exposed to natural but primarily man-made chemicals that can interfere with their endocrine system and thereby adversely affect vertebrate physiology and development especially in aquatic vertebrates. Such chemicals are called endocrine disrupting compounds. Besides affecting the thyroid system, the stress hormone system, and the immune system, EDCs can especially interfere with the hypothalamic-pituitary-gonad axis and affect various aspects of reproduction via estrogenic and androgenic modes of action.

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