The efficacy and safety of entecavir in patients with chronic hepatitis B- associated liver failure: a meta-analysis.

BACKGROUND: The effectiveness of nucleoside analogue (NA) treatment in patients with chronic hepatitis B (CHB) -associated liver failure is still controversial. Severe lactic acidosis has been reported during entecavir (ETV) treatment in patients with impaired liver function. AIM: To investigate the rescuing efficacy and safety of ETV in patients with CHB-associated liver failure. MATERIAL AND METHODS: A literature search was carried out to collect articles dated up to December, 2013 on ETV therapy for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was used as the primary efficacy measure. The safety of ETV was assessed. RESULTS: Six randomized controlled trials were selected. The overall analysis revealed ETV significantly improved survival at 4 weeks (RR = 1.35; 95% CI [1.16, 1.57]; p < 0.0001), 8 weeks (RR = 1.33; 95% CI [1.07, 1.64]; p = 0.009), 12 weeks (RR = 1.68; 95% CI [1.24, 2.28]; p = 0.0008). Pooled data also showed beneficial effects of antiviral therapy compared with control for HBV DNA negative change (RR = 5.35; 95% CI [2.06, 13.88]; p = 0.0006), TBIL and PTA improvement (TBIL: MD = -69.36; 95% CI [-134.37, -4.36]; p = 0.04. PTA: MD = 16.26; 95% CI [8.59, 23.94]; p < 0.0001). No adverse effect was identified in the examined studies. CONCLUSION: Our results showed that antiviral therapy with ETV improved the short-term survival of patients with CHB-associated liver failure. In addition, ETV was well tolerated during the treatment period. Further studies are still needed to strengthen these results.

Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Saikosaponins B2 (SSB2) is one of the main active components isolated from Radix Bupleuri (Bupleurum chinense DC.), a herb widely used of traditional Chinese medicine. It has been used for the treatment of depression for more than two thousand years. However, the molecular mechanisms remain to be determined. AIM OF THE STUDY: In this study, we evaluated the anti-inflammatory effect and elucidated underlying molecular mechanisms of SSB2 in LPS-induced primary microglia and CUMS-induced mice model of depression. METHOD: The effects of SSB2 treatment were investigated both in vitro and in vivo. The chronic unpredictable mild stimulation (CUMS) procedure was applied to establish the animal model of depression. Behavioural tests were used to evaluate the depressive-like behaviors in CUMS-exposed mice, including sucrose preference test, open field test, tail suspension test, and forced swimming test. The GPX4 gene of microglia was silenced using shRNA, and inflammatory cytokines were determined by Western Blot and immunofluorescence analysis. Endoplasmic reticulum stress and ferroptosis-related markers were detected by qPCR, flow cytometry and confocal microscopy. RESULT: SSB2 reversed depressive-like behaviours in CUMS-exposed mice and relieved central neuroinflammation and ameliorated hippocampal neural damage. SSB2 alleviated LPS-induced activation of microglia through the TLR4/NF-κB pathway. LPS-induced ferroptosis, with increased levels of ROS, intracellular Fe2+, mitochondrial membrane potential, lipid peroxidation, GSH, SLC7A11, FTH, GPX4 and Nrf2, and decreased transcription levels of ACSL4 and TFR1, was attenuated with SSB2 treatment in primary microglia cells. GPX4 knockdown activated ferroptosis, induced endoplasmic reticulum (ER) stress, and abrogated the protective effects of SSB2. Further, SSB2 attenuated ER stress, balanced calcium homeostasis, reduced lipid peroxidation and intracellular Fe2+ content by regulating the level of intracellular Ca2+. CONCLUSIONS: Our study suggested that SSB2 treatment can inhibit ferroptosis, maintain calcium homeostasis, relieve endoplasmic reticulum stress and attenuate central neuroinflammation. SSB2 exhibited anti-ferroptosis and anti-neuroinflammatory effects through the TLR4/NF-κB pathway in a GPX4-dependent manner.

[Study of blood compatibility on TiO2 coated biomedical Ni-Ti shape memory alloy].

We coated a thin TiO2 film on the surface of Ni-Ti shape memory alloy by activated sputter method in the present work. The blood platelet adherence and antithrombogenicity of the TiO2-coated Ni-Ti alloy were evaluated. The results showed that the platelets on the TiO2-coated Ni-Ti alloy were fewer than those on 316L stainless steel, and no agglomeration or distortion for the platelets on the coated alloy was found, which means less probability of blood coagulation for the alloy. The coagulation time on the coated Ni-Ti shape memory alloy was longer than that on the 316L. Compared with that on the 316L stainless steel, the TiO2 coated Ni-Ti shape memory alloy showed better blood compatibility, indicating that the Ni-Ti alloy with TiO2 coating is a kind of ideal biomedical materials with high clinical value.

Different mutations at position 562 of the hepatitis E virus capsid proteins exhibit differential effects on viral neutralizing activity.

The hepatitis E virus (HEV) capsid protein pORF2 comprises three potential N-linked glycosylation sites. One site, N562, is located at the cell attachment and neutralizing antigenic regions. The present study performed detailed analyses of the effects of specific amino acid substitutions at position 562 in the homodimerization, glycosylation, antigenicity, immunogenicity and neutralization activities of HEV pORF2. Recombinant HEV pORF2 glycoprotein E1 (amino acids 439-617) and three mutant variants (N562L, N562C and N562K) were expressed in Pichia pastoris (P. pastoris) and SDS-PAGE, Western blot analysis, tunicamycin assay, double-antibody sandwich ELISA and in vitro PCR-based neutralization assay were performed to characterize the different constructs. All proteins were indicated to be secreted by P. pastoris and formed homodimers. Tunicamycin assay revealed the glycosylated status of the wild-type protein, but the mutants were indicated to be non-glycosylated. All proteins were immunoreactive with a neutralizing monoclonal antibody but were not recognized by the antibody after denaturation into monomers. An in vitro PCR-based neutralization assay using mouse antibodies indicated efficient neutralization against N562L, whereas antibodies against N562C and N562K were revealed to be non-neutralizing. Collectively, the present study indicated that specific amino acid substitutions at position 562 serve crucial roles in the activity of the HEV neutralizing epitope.

[Preparation of anodic oxidation layer on the surface of pure titanium and its biological activity study].

This paper introduces how TiO2 film was prepared on pure titanium by anodic oxidation. Surface morphology and composition of the oxide film were analyzed by SEM coupled with EDAX. The deposition ability of hydroxyapatite of the anodized titanium in simulated body fluid (SBF) at 37 degrees C was evaluated. The results indicated that the oxide film was rough and honeycomb holes, connecting with each other, could be found on the surface. The holes with the diameter of 1-2 microm were distributed uniformly, which was typical for anodic oxidation. After alkaline treatment, hydroxyapatite deposition on the oxidized specimens in SBF was improved significantly.

Intracellular levels of hepatitis B virus DNA and mutational patterns of the polymerase gene of hepatitis B virus in peripheral blood mononuclear cells of patients with lamivudine or telbivudine resistance.

Studies are limited regarding the association between the quantity of hepatitis virus B (HBV) DNA loads in serum and peripheral blood mononuclear cells (PBMCs) in patients with drug resistance and few studies focus on the mutational pattern of the polymerase gene of HBV in PBMCs of patients with drug resistance. The aim of the present study was to investigate the association between the quantity of HBV DNA loads in serum and PBMCs in patients with lamivudine (LAM) or telbivudine (LdT) resistance and to explore the mutational pattern of the polymerase gene of HBV in PBMCs of these patients. A total of 51 patients underwent antiviral therapy with LAM or LdT for at least half a year. The present study applied quantitative polymerase chain reaction for the quantification of total HBV DNA, and direct sequencing was used to detect the mutation. In total, 31 patients (60.78%) were detected to have drug resistance. The mean serum HBV DNA levels were significantly higher than the HBV DNA levels of PBMCs, whether in patients with LAM or LdT resistance. The PBMCs HBV DNA loads were correlated with the serum HBV DNA loads in the two groups. Three and two mutational patterns were found in the serum of patients with LAM and LdT resistant, respectively. In total, 85.71% of patients with LAM resistance and 75.00% of patients with LdT resistance presented the same mutational pattern in paired PBMCs and serum. The HBV DNA levels in the PBMCs of patients with LAM or LdT resistance were significantly lower than those in serum and there were positive correlations between them. The majority of the mutational patterns of the polymerase gene of HBV DNA in PBMCs were the same as those in the paired serum. These findings may help to increase knowledge regarding HBV drug resistance.