In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α), the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR)-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR) and in 28 non-responder(NR) to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

BackgroundThe purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters.MethodsLiver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF.ResultsThe mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity.ConclusionsThe LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.

It has recently been demonstrated that toll-like receptors (TLRs) can recognize structural conserved motifs carried by circulating microbial products and lead to systemic immune responses in individuals infected with HIV-1. TLRs have been detected in CD8(+) T cells at either a protein or RNA level. The role of TLRs on CD8(+) T cells involved in the host's immune responses during HIV-1 infection has not been well characterized. In this study, we analyzed expression of TLR4, TLR5, TLR7, and TLR8 in CD8(+) T cells in HIV-1 infection. All these four TLRs could be detected in CD8(+) T cells, but only TLR7 in CD8(+) T cells from HIV-1-infected individuals showed a higher expression level compared with that from healthy individuals (p < 0.05). The function of TLR7 in CD8(+) T cells was then investigated. We found that TLR7 ligand responsiveness significantly increased the expression of immune activation markers on purified CD8(+) T cells in HIV-1-infected individuals compared with healthy controls. And the levels of these markers were equivalent to those achieved by CD8(+) T cells from peripheral blood mononuclear cells (PBMCs). However, we also observed that TLR7 ligand stimulated significant IFN-gamma production by CD8(+) T cells in an accessory cell-dependent manner. Therefore, although CD8(+) T cells can be directly activated by TLR7, accessory cells must play an essential role in the activation of effective functions such as IFN-gamma production. These findings suggest that the abnormal expression of TLR7 in CD8(+) T cells from HIV-1-infected individuals may contribute to the abnormal immune activation in HIV-1 infection and play an important role in HIV-1 pathogenesis.

A novel role for calcineurin (Cn) has been reported recently regarding the oncogenic potential in pancreatic and colorectal cancer. The aim of this study was to investigate the putative causal role calcineurin could play in the development of lung cancer with bone metastases. We found that CnAalpha, an isoform of calcineurin, was significantly overexpressed in lung cancer tissues with bone metastasis as compared to tumors with non-bone metastases as investigated by RT-PCR. Strong nuclear staining of tumor cells was observed in small cell lung cancer tissues with bone metastasis. Conversely, cytoplasmic staining of tumor cells was observed in small cell lung cancer tissues with non-bone metastasis. Western blots of nuclear proteins from lung cancer tissues indicated that CnAalpha was highly expressed in lung cancer tissues with bone metastases, but not in those with non-bone metastases. In vitro, it was demonstrated that the CnAalpha gene obviously promoted cell proliferation and inhibited cell apotosis. The CnAalpha gene affected the cell cycle and promoted G1[Symbol: see text]S transition in SBC-3 cells. Transfection with the CnAalpha gene promoted cell migration and invasion. These results indicated that CnAalpha may affect the biological behavior of the human small cell lung cancer cell line SBC-3 in vitro and may be a candidate tumor promotor gene for developing bone metastases.

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