Re-Arterialized Rat Partial Liver Transplantation with an <em>in vivo</em> Vessel-Oriented 70% Hepatectomy

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

The First Affiliated Hospital of Wenzhou Medical University

Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. MicroRNAs have been shown to play a pivotal role in regulating HSC functions such as cell proliferation, differentiation, and apoptosis. Recently, miR-181b has been reported to promote HSCs proliferation by targeting p27. But whether alpha-smooth muscle actin (α-SMA) or collagens could be promoted by miR-181b in activated HSCs is still not clear. Therefore, the understanding of the role of miR-181b in liver fibrosis remains limited. Our results showed that miR-181b expression was increased much higher than miR-181a expression in vitro in transforming growth factor-β1-induced HSC activation as well as in vivo in carbon tetrachloride-induced rat liver fibrosis. Of note, overexpression of miR-181b significantly increased the expressions level of α-SMA and type I collagen, and further promoted HSCs proliferation. Furthermore, phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of PI3K/Akt pathway, were confirmed as a direct target of miR-181b. We demonstrated that miR-181b could suppress PTEN expression and increase Akt phosphorylation in HSCs. Interestingly, the effects of miR-181b on the activation of HSCs were blocked down by Akt inhibitor LY294002. Our results revealed a profibrotic role of miR-181b in HSC activation and demonstrated that miR-181b could activate HSCs, at least in part, via PTEN/Akt pathway.

Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway.

It has been demonstrated that liver microRNA-125a-5p (miR-125a-5p) is correlated with disease progression in different liver diseases, including liver fibrosis and hepatocellular carcinoma (HCC). The present study investigated whether serum miR-125a-5p correlated with the progression of different liver diseases. Serum samples were obtained from healthy individuals, patients with chronic hepatitis B who had undergone a liver biopsy, and patients with HCC and were analyzed for the levels of miR-125a-5p. Compared with the healthy controls, the serum levels of miR-125a-5p were significantly higher in the liver fibrosis serum, and were reduced in HCC. With the development of liver fibrosis, there was a significant increase in the expression of miR-125a-5p (P<0.05). In comparing histological activity index (HAI) scores, higher expression levels of miR125a-5p were observed in the high HAI score group (P<0.05). Furthermore, correlation between serum miR-125a-5p and viral replication (P<0.001) was observed. Notably, miR-125a-5p demonstrated significant correlation with other markers in the liver fibrosis group (P<0.001). In the patients with HCC, lower serum levels of miR-125a-5p were correlated with a poor prognosis, determined by Kaplan-Meier curve analysis (P=0.009). In the liver fibrosis and HCC groups, different expression levels of serum miR-125a-5p were observed, and were correlated with disease progression. The results of the present study suggested that serum miR-125a-5p may be used as a non-invasive biomarker for monitoring disease progression in liver diseases.

Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression.

Tadalafil can restore endothelial function and treat atherosclerosis. However, the effect of tadalafil on transplant arteriosclerosis remains unclear. In this study, we explore the effects of tadalafil on allograft vasculopathy.

Tadalafil attenuates graft arteriosclerosis of aortic transplant in a rat model.

Aberrant Wnt/β-catenin pathway contributes to the development of liver fibrosis. MicroRNAs (MiRNAs) are found to act as regulators of the activation of hepatic stellate cell (HSC) in liver fibrosis. However, whether miRNAs activate Wnt/β-catenin pathway in activated HSCs during liver fibrosis is largely unknown. In this study, we found that Salvianolic acid B (Sal B) treatment significantly inhibited liver fibrosis in CCl4-treated rats, HSC-T6 cells and rat primary HSCs, resulting in the suppression of type I collagen and alpha-smooth muscle actin. Also, Sal B suppressed HSC activation and cell proliferation in vitro. Interestingly, Sal B treatment induced the inactivation of Wnt/β-catenin pathway, with an increase in P-β-catenin and Wnt inhibitory factor 1 (WIF1). We demonstrated that the anti-fibrotic effects caused by Sal B were, at least in part, via WIF1. Moreover, our study revealed that miR-17-5p was reduced in vivo and in vitro after Sal B treatment. As confirmed by luciferase activity assays, WIF1 was a direct target of miR-17-5p. Notably, the suppression of HSCs induced by Sal B was almost inhibited by miR-17-5p mimics. Collectively, we demonstrated that miR-17-5p activates Wnt/β-catenin pathway to result in HSC activation through inhibiting WIF1 expression.

MicroRNA-17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis.

To evaluate the effects on filtration membrane of glomerulus after islet transplantation in a rat model of streptozotocin-induced diabetic nephropathy.

Islet transplantation restores the damage of glomerulus filtration membrane in a rat model of streptozotocin-induced diabetic nephropathy.

                    
. Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN.. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group), the insulin-treated group (IN group), and the untreated group (DN group). Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM) detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels.. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM) were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased.. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.

Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model.

                    
Transplant arteriosclerosis is considered one of the major factors affecting the survival time of grafts after organ transplantation. In this study, we proposed a hypothesis of whether lycopene can protect grafted vessels through regulating key proteins expression involved in arteriosclerosis.Allogeneic aortic transplantation was performed using Brow-Norway rats as donors and Lewis rats as recipients. After transplantation, the recipients were divided into two groups: the allograft group and the lycopene group. Negative control rats (isograft group) were also established. Histopathological staining was performed to observe the pathological changes, and the expression levels of Ki-67, caspase-3, Rho-associated kinases, intercellular adhesion molecules (ICAM-1), and eNOS were assessed. Western blotting analysis and real-time PCR were also performed for quantitative analysis.The histopathological staining showed that vascular stenosis and intimal thickening were not evident after lycopene treatment. The Ki-67, ROCK1, ROCK2, and ICAM-1 expression levels were significantly decreased. However, eNOS expression in grafted arteries and plasma cGMP concentration were increased after lycopene treatment.Lycopene could alleviate vascular arteriosclerosis in allograft transplantation via downregulating Rho-associated kinases and regulating key factor expression through the NO/cGMP pathways, which may provide a potentially effective method for transplant arteriosclerosis in clinical organ transplantation.

Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho-Associated Kinases Expression.

The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats.

The role of sirolimus in proteinuria in diabetic nephropathy rats.

Prostate cancer is the most frequently diagnosed malignancy in men and the second major reason of cancer death in males. Currently, there are no viable options available for the treatment of advanced-stage prostate cancer. Against this backdrop, the present study aimed to study the anticancer effect of panaxatriol against prostate DU-15 cancer cells.

Potential antitumor effects of panaxatriol against DU-15 human prostate cancer cells is mediated via mitochondrial mediated apoptosis, inhibition of cell migration and sub-G1 cell cycle arrest.

Ziqiang Xu

Department of Transplantation

The First Affiliated Hospital of Wenzhou Medical University

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Ziqiang Xu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Transplantation

The First Affiliated Hospital of Wenzhou Medical University

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Department of Transplantation