Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, Ecadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAgpositive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of b-catenin in the cytoplasm and/ or nuclei in tissues and cell lines, which is characteristic of activated b-catenin. Additional work showed that HBxAg-activated b-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of b-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.

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Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA-DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV-infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA-DRB1*03 [10.6% of HBV-infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA-DRB1*07 (17.6% of HBV-infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV-infected group. But the allele frequencies of HLA-DRB1*15 (6.9% of HBV-infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA-DRB1*03 and HLA-DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV-infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high-risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.

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Three-dimensional (3D) highly porous poly (DL-lactic-co-glycolic acid)/tricalcium phosphate (PLGA/TCP) scaffolds were fabricated using a rapid prototyping technique (RP). The biopolymer carriers (4mm×4mm×4mm) subsequently were coated with collagen type I (Col) to produce PLGA/TCP/Col composites and utilized as an extracellular matrix for a cell-based strategy of bone tissue engineering. Autologous bone marrow stromal cells (BMSCs) harvested from New Zealand white rabbits were cultured under an osteogenic condition (BMSCs-OB) followed by seeding into the structural highly porous PLGA/TCP/Col composites (i.e. PLGA/TCP/Col/BMSCs-OB). Scanning electron microscopy observation found that the RP-based scaffolds had appropriate microstructure, controlled interconnectivity and high porosity. Modification of the scaffolds with collagen type I (PLGA/TCP/Col) essentially increased the affinity of the carriers to seeding cells, and PLGA/TCP/Col composites were well biocompatible with BMSCs-OB. The PLGA/TCP/Col/BMSCs-OB constructs were then subcutaneously implanted in the back of rabbits compared to controls with autologous BMSCs suspension and carriers alone. As a result, histological new bone formation was observed only in the experimental group with PLGA/TCP/Col/BMSCs-OB constructs 8 weeks after implantation. In the control group with scaffold alone only biodegradation of the carriers was found. Therefore, these results validate our bio-manufacturing methods for a new bone graft substitute.