This study aims to verify whether rat hepatic stellate cells (HSCs) promote the differentiation of rat adipose-derived stem cells (rADSCs) into endothelial cells (ECs) by activating the bone morphogenetic protein 4 (BMP4) signaling pathway and prepare seed cells for the reendothelialization of decellularized liver scaffold with the HSCs and rADSCs co-culture system. After co-culture of HSCs and rADSCs for 2 w and induction with vascular endothelial growth factor (VEGF), we observed that HSCs promote rADSC-derived ECs to express high levels of EC markers, such as eNOS, and enhance EC migration and DiI-Ac-LDL uptake, resulting in the formation of a vascular network-like structure. Immunofluorescence and western blotting results demonstrated that HSCs promote VEGF-induced differentiation of rADSCs into ECs by enhancing Smad1/5 phosphorylation levels via BMP4 upregulation. Thus, HSCs promote rADSC differentiation into ECs by activating BMP4 signaling, potentially providing reliable theoretical guidance and suggesting an extensive research strategy for reendothelialization of the decellularized liver scaffold and rebuilding the functional vascularization of tissue-engineered liver.
Hepatocellular carcinoma (HCC) is the fifth most common worldwide tumor and is the third most common cause of cancer-related deaths in the world and in China (Cha et al., 2012; Takeuchi et al., 2012; Yang et al., 2012). Various factors have been associated with the initiation and development of HCC,including chronic infection of hepatitis viruses;age;sex;alcohol abuse;aflatoxin; diabetes mellitus and hereditary metabolic liver diseases (Zha et al., 2012). However,there is a lack of sensitive and specific biomarkers in the clinic, the existing early-stage screening strategies have limited benefits to the detection of HCC until multicentric recurrence and intrahepatic metastasis (Li et al., 2012). So even with advanced treatments, such as surgery, chemotherapy, and radiotherapy, HCC still presents a poor prognosis.Therefore, it is critical to identify important prognostic factors and to develop novel therapeutic strategies targeting HCC. Being similar to most other kinds of tumor,hepatocarcinogenesis is a complex process,such as the activation of oncogenes and the inactivation of tumor suppressor genes,involving genic alterations and mutations, which ultimately lead to the malignant transformation of hepatocytes (Zha et al., 2012). The serine–threonine kinase liver kinase B1 (LKB1;
In order to improve the performance of Gigabit Passive Optical Network(GPON) systems, a novel dynamic bandwidth allocation(DBA) scheme called P-DBA based on traffic prediction for GPON is proposed, which can better meet the optical network's technical requirements of high bandwidth, low delay and low packet loss rate. Using the high-order moving average model, P-DBA scheme predicts the amount of high-priority traffic arriving during the waiting period, as a basis for bandwidth allocation, so as to ensure the performance of high priority services. Simulation results show that the P-DBA scheme proposed in this paper has good performances on latency and packet loss rate.
Objective To investigate the effect and the potential mechanism of splenic artery coarctation on the expression of iNOS and Th1/Th2 cytokines in spleen of cirrhotic rats with portal hypertension (PHT). Methods Cirrhotic rats were randomized into 3 groups (n= 10):sham operation group (SOG), splenic artery coarctation group (SAC) and splenic artery ligation group (SAL). Ten normal rats treated with sham operation were employed to serve as normal control group (NCG). Immunohistochemial staining was used to observe iNOS. RT-PCR was used to detect IFN-γ and IL-4mRNA. The Pearson's correlation analysis was used to investigate the relationship between iNOS and IFN-γ or IL-4. Results The expression of iNOS was increased significantly in spleen of cirrhotic rats as compared with NCG(P<0. 01). It was decreased after SAC and SAL compared with SOG (P<0. 01). The expression of IFN-γmRNA and IFN-γ/IL-4 of SOG were decreased but IL-4mRNA increased significantly than that of NCG(P<0.01). IFN-γmRNA was increased after SAC compared with SOG (P<0.05). IL-4mRNA was decreased and IFN-γ/IL-4 increased after SAC and SAL compared with SOG (P<0. 05). The expression of iNOS was negatively correlated with the expression of IFN-γmRNA(r=-0.672, P< 0.01 ) and positively correlated with the expression of IL-4 mRNA (r=0.634,P<0. 01). Conclusion The expression of iNOS is decreased and IFN-γ/IL-4 increased after SAC in spleen of cirrhotic rats with PHT and it may improve Th1/Th2 polarization by reducing the expression of iNOS.
Objective To study a new method of puncturing biliopancreatic duct injection on rat model with severe acute pancreatitis (SAP). Methods Sixty SD rats were randomly divided into two groups: the SAP group (n=30) and the control group (n=30). The SAP model was induced by the new method of retrograde injection of 5% sodium taurocholate into biliopancreatic duct after biliopancreatic duct punctured (to be abbreviated as the new method of puncturing biliopancreatic duct injection). All animals were sacrificed at 1, 3, 6, 12, 24 hours, respectively, after the onset of induction. Then rat mortality, ascites volume, serum amylase and function of liver, kidney, heart were examined in each group. Histological change of pancreas was also evaluated. Results The mortality of SAP group at 24 hours was 16.67% . Levels of ascites volume, serum amylase (AMY), alanine aminotransferase (ALT) , blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CKMB) and histological scoring in SAP group were all significantly higher than those of the control group at each time point (P0.05). And data were in stabile kinetic variance. Conclusion The new method of puncturing biliopancreatic duct injection can establish a simple and reliable SAP with clinical pathogenesis on rats.
We used immunohistochemical staining to assess protein over-expression of glial cell-derived neurotrophic factor (GDNF) and its RET receptor tyrosine kinase in patients with pancreatic cancer and benign pancreatic neoplasm, and assessed correlations with clinicopathological features and prognosis. Surgically resected pancreatic cancer patients (40/58, 68.9%) showed positive GDNF immunostaining, a significantly higher frequency than in patients with benign pancreatic tumour (3/11, 27.3%). Intrapancreatic neural invasion by cancer cells was significantly related to over-expression of GDNF. Strongly positive expression of GDNF was significantly more frequent than lesser grades of expression in patients with severe back pain before and 12 months after surgery. Expression of RET was significantly related to lymphatic invasion, survival rate after tumour resection and degree of tumour cell differentiation. We conclude that GDNF may be important in pancreatic cancer proliferation and metastasis, especially in patients with perineural invasion. Strongly positive expression of GDNF may be an indication for early intensified radiotherapy. RET expression in pancreatic cancer tissues may be a useful prognostic marker.