Prognostic performance of a series of model for end-stage liver disease and respective Δ scores in patients with hepatitis B acute-on-chronic liver failure.

The present study aimed to compare the short-term prognostic performance of a series of model for end-stage liver disease (MELD) and respective delta (∆) scores scoring systems in a population with acute-on-chronic hepatitis B liver failure (ACHBLF), and to investigate the potential effects from antivirals. A total of 77 patients with ACHBLF of mean age 46 years, 82% male, with 58.4% receiving antivirals, were recruited for this study. The ∆ scores for MELDs were defined as the changes one week after admission. Thirty­eight (49%) patients (22 treated with antivirals) died within three months. The mean MELD and ∆MELD scores of the survival group were 19.5 ± 4.4 and 0.2 ± 3.7 respectively, and those of the mortality group were 23.5 ± 5.5 and 7.9 ± 6, respectively. The area under the receiver operating characteristic curve (AUC) for MELD, integrated MELD (iMELD), MELD with the addition of serum sodium (MELD-Na), updated MELD (upMELD), MELD excluding the international normalized ratio (INR; MELD-XI), United Kingdom MELD (UKMELD) and their ∆ scores were 0.72, 0.81, 0.77, 0.69, 0.65, 0.77 and 0.86, 0.83, 0.83, 0.82, 0.79 and 0.79, respectively. iMELD and MELD-Na significantly improved the accuracy of MELD (P<0.05). A cut-off value of 41.5 for the iMELD score can prognose 71% of mortalities with a specificity of 85%. In each pair of models, the ∆ score was superior to its counterpart, particularly when applied to patients with MELD ≤ 30. Decreased accuracy was observed for all models in the subset of patients treated with antivirals, although their baseline characteristics were comparable to those of untreated patients, while iMELD, MELD-Na and respective ∆ models remained superior with regard to the predictability. The iMELD and MELD-Na models predicted three-month mortality more accurately, while the ∆ models were superior to their counterparts when MELD ≤ 30; however, their performance was altered by antivirals, and thus requires optimization.

Lentivirus-mediated silencing of rhomboid domain containing 1 suppresses tumor growth and induces apoptosis in hepatoma HepG2 cells.

Rhomboids were identified as the first intramembrane serine proteases about 10 years ago. Since then, the study of the rhomboid protease family has blossomed. Rhomboid domain containing 1 (RHBDD1), highly- expressed in human testis, contains a rhomboid domain with unknown function. In the present study, we tested the hypothesis that RHBDD1 was associated with proliferation and apoptosis in hepatocellular carcinoma using recombinant lentivirus-mediated silencing of RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA levels markedly suppressed proliferation and colony formation capacity of HepG2 human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In summary, it was demonstrated that RHBDD1 might be a positive regulator for proliferative and apoptotic characteristics of hepatocellular carcinoma.

Inhibition of Csn3 expression induces growth arrest and apoptosis of hepatocellular carcinoma cells.

PURPOSE: Csn3 (or CSN3) encodes the third subunit of an eight-subunit complex, the COP9 signalosome (CSN), which acts as a protein kinase and a deneddylase in mammalian cells. Previous studies have shown that Csn3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast and associated with the tumorigenesis process in osteosarcoma. However, its correlation with hepatocellular carcinoma (HCC) has not been explored yet. METHODS: The expression of Csn3 in HCC (n = 30), cirrhosis (n = 30), and normal tissues (n = 30) was detected using immunohistochemical analysis. The impacts of lentivirus-mediated inhibition of Csn3 on HCC cells were detected using MTT, BrdU incorporation assay, and flow cytometric analysis. In addition, the colony formation and tumor growth ability in nude mice were detected to define the role of Csn3 in tumorigenesis. RESULTS: Knockdown of Csn3 expression in HCC cell lines (SMMC-7721 and Hep3B) significantly inhibits the tumor growth both in vitro and in vivo. Further investigation indicates that this growth inhibition effect may be mediated through cell cycle arrest in G0/G1 phase and inductions of pro-apoptotic proteins BIK and Caspase-8. In addition, knockdown of Csn3 expression evidently suppresses tumor growth in a xenograft nude mice model. CONCLUSION: Collectively, this study demonstrates Csn3 as an oncogene that regulates the tumorigenesis process in HCC cells.

[HBcAg-specific CTL response induced by PTD-HBcAg fusion protein to inhibit HBV replication in vitro].

AIM: To investigate the effects of specific cytotoxic T lymphocyte induced by sensitized dendritic cells(DCs)with PTD-HBcAg fusion protein on inhibiting HBV in vitro. METHODS: DCs were cultured and induced maturation by different fusion proteins, and cocultured with allogeneic T cells to detect the secretion level of IL-2, IL-4, IL-10 and INF-gamma in the supernatants of T cells by ELISA. Intracellular cytokine of proliferative T cells was analyzed by flow cytometry and the specific CTL activity was measured by a lactate dehydrogenase (LDH) release assay. The levels of HBsAg and HBV DNA in the supernatant of HepG2.2.15 cells were detected. RESULTS: Sensitized dendritic cells by different fusion proteins could promote cytokine secretion effectively, the levels of IL-2(552.7+/-117.5 ng/L) and INF-gamma(150.6+/-7.945 ng/L)induced by M-PTD-HBcAg were higher than that induced by M-HBcAg (420+/-12.47 ng/L and 107.5+/-12.19 ng/L, respectively).The amount of CTLs induced by PTD-HBcAg fusion protein was more than others by the analysis of intracellular cytokine of proliferative T cells. Specific CTL killing activity could be induced by PTD-HBcAg and HBcAg(P<0.05) and PTD-HBcAg significantly decreased the levels of HBsAg and HBV DNA. CONCLUSION: Sensitised DCs by PTD-HBcAg fusion protein can stimulate cytokine secretion and increase cytotoxic T lymphocytes generation effectively, and also enhance the specific CTL activity to decrease the level of HBsAg and HBV DNA in supernatants of HepG2.2.15 cells.