Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

Background And Aim: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.

Interferon-α-induced CD100 on naïve CD8 T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction.

Objectives We investigated the effects of CD100 on naïve CD8 T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8 T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8 T cells were determined with ELISAs and an MTT cytotoxicity assay.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

Background: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions.

Methods: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs).

Competitive binding between miR-122 and p68 onto hepatitis C viral RNA.

Background: Liver-specific microRNA (miR)-122 has been shown to be involved in regulating translation of hepatitis C viral (HCV) RNA. This study aimed to explore the molecular mechanism of miR-122 in regulating HCV RNA translation initiation.

Material/methods: In human liver hepatocellular carcinoma cell line HepG2, UV cross-link assay was performed on a large scale to identify RNA-binding proteins with gradient concentrations of miR-122.

[Clinical characteristics of pediatric hemorrhagic fever with renal syndrome].

Objective: To study the clinical characteristics of pediatric hemorrhagic fever with renal syndrome (HFRS), and to improve its understanding so as to reduce the misdiagnosis.

Methods: A retrospective analysis was performed on the clinical data of 26 children with HFRS between January 2009 and December 2012.

Results: The age of disease onset was mainly distributed between 7 and 14 years (23 cases, 88%), and the male-to-female ratio was 1.

[Generation of six genotypes of infectious HCV pseudo-particles and detection of neutralizing antibodies in HCV patients].

Objective: To generate hepatitis C virus pseudo-particles (HCVpp) containing the complete E1-E2 envelope glycoprotein, in order to establish a HCVpp database covering the six major genotypes of HCV (1b, 2a, 3b, 4, 5, and 6) and to develop a simple and effective method for detection of neutralizing antibodies in HCV patients.

Methods: HCVpp were generated for the six genotypes by co-transfecting 293T cells with a plasmid expressing the respective E1-E2 (p HR, CMVA 8.2 construct) and a MLV-GFP plasmid.

Identification of peptides that bind hepatitis C virus envelope protein E2 and inhibit viral cellular entry from a phage-display peptide library.

Hepatitis C virus (HCV) envelope protein E2 is required for the entry of HCV into cells. Viral envelope proteins interact with cell receptors in a multistep process, which may be a promising target for the development of novel antiviral agents. In this study, a heptapeptide M13 phage-display library was screened for peptides that bind specifically to prokaryotically expressed, purified truncated HCV envelope protein E2.

S100A14 promotes the growth and metastasis of hepatocellular carcinoma.

Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC).

Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed.

Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice.

To develop a vaccine against hepatitis C virus (HCV), a multi-epitope peptide was synthesized from nonstructural proteins containing HLA-A2 epitopes inducing mainly responses in natural infection. The engineered vaccine candidate, VAL-44, consists of multiple epitopes from the HCV NS5A, NS4B and core proteins. Immunization with the VAL-44 peptide induced higher CTL responses than those by the smaller VL-20 peptide.

[Peg-IFNa-2a/RBV antiviral efficacy in cirrhotic hepatitis C patients after splenectomy or partial splenic embolization].

To investigate the antiviral efficacy of combination therapy with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) in hepatitis C patients with liver cirrhosis after splenectomy or partial splenic embolization. Forty-nine hepatitis C patients with liver cirrhosis who were unable to use antiviral therapy because of hypersplenism were recruited for study and treated with splenectomy or partial splenic embolization. Three months later, a regimen of antiviral combination therapy was initiated with peg-IFNa-2a (once-weekly subcutaneous injection: 135 μg or 180 μg) and RBV (daily oral: 800 to 1200 mg), and was maintained for 48 weeks.

Prohibitin is overexpressed in Huh-7-HCV and Huh-7.5-HCV cells harboring in vitro transcribed full-length hepatitis C virus RNA.

Background: Currently, up-regulated proteins and apoptosis in hepatitis C is a hot topic in exploring the pathogenic mechanism of Heptitis C Virus(HCV). Some recent studies shows that prohibitin is overexpressed in cells expressing HCV core proteins, and up-regulated prohibitin is also found in human hepatoma cell line HCC-M, lung cancer, prostate cancer, and other cancers. Prohibitin is an important member of the membrane protein superfamily, and it plays a role of molecular chaperones in mitochondrial protein stability.

Association of parvovirus B19 infection with acute icteric hepatitis in adults.

Infection by human parvovirus B19 is widespread and can be associated with a wide range of different pathologies and clinical manifestations. However, parvovirus B19 infection associated with hepatitis or hepatic dysfunction in adults is rarely reported. We describe two cases of acute icteric hepatitis associated with parvovirus B19 infection in adults.

[Preparation of anti-ASNS monoclonal antibody and detection of ASNS expression in tumor].

Aim: To prepare and characterize monoclonal antibodies against ASNS for the research of ASNS function.

Methods: To induce the expression of the fusion protein MS2-ASNS, Hybridomas were generated by the fusion with Sp2/0 myelomas and spleen cells, which were obtained from mice immunized with MS2-ASNS recombinant proteins. The specificity and titer of mAb were identified by ELISA methods, and then used to detect the affinity of ASNS in cancer cells by Western blot.

Analysis of the immune response to Hantaan virus nucleocapsid protein C-terminal-specific CD8(+) T cells in patients with hemorrhagic fever with renal syndrome.

Hantaan virus (HTNV), the prototype member of the Hantavirus genus in the family Bunyaviridae, causes hemorrhagic fever with renal syndrome (HFRS), which is characterized by capillary leakage, hemorrhage, and renal injury, and is an important public health problem in China. Some kinds of immune cells, particularly CD8(+) T cells, are involved in the pathogenesis of Hantavirus infection. The nucleocapsid protein (NP) of the Hantavirus is the most conserved structural protein and the most abundant viral protein produced during infection.

Down-regulation of CXCR4 expression by SDF-KDEL in CD34(+) hematopoietic stem cells: An anti-human immunodeficiency virus strategy.

CXCR4 plays an essential role as the first discovered coreceptor for the entry of T cell tropic isolates of HIV-1. Blocking the surface expression of this receptor may be a potential strategy to prevent HIV-1 infection. A lentiviral vector, pLenti6/V5-S-K, expressing a SDF-KDEL fusion protein was constructed and a replication-incompetent lentiviral stock was produced.

Lipopolysaccharide-induced maturation of bone marrow-derived dendritic cells is regulated by notch signaling through the up-regulation of CXCR4.

Dendritic cells (DCs) are professional antigen presenting cells to initiate immune response against pathogens, but mechanisms controlling the maturation of DCs are unclear. Here we report that, in the absence of recombination signal binding protein-Jkappa (RBP-J, the transcription factor mediating Notch signaling), lipopolysaccharide-stimulated monocyte-derived DCs are arrested at a developmental stage with few dendrites, low major histocompatibility complex II (MHC II) expression, and reduced motility and antigen presentation ability. RBP-J null DCs had lower expression of CXCR4.

Inhibition of hepatitis C virus infection by interferon-gamma through downregulating claudin-1.

Hepatitis C virus (HCV) is a serious global health threat and current medical treatment options are limited. Interferon (IFN)-gamma is an important proinflammatory cytokine with antiviral activity. However, the mechanism of IFN-gamma in anti-HCV infection remains unclear.

Hantaan virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon, interleukin-6 and tumor necrosis factor-alpha.

Hantaan virus (HTNV) infects endothelial cells and is associated with increased vascular permeability during hemorrhagic fever with renal syndrome (HFRS). The pattern of increased vascular permeability is mediated by immune response. Therefore, it is necessary to characterize the mechanism of HTNV involvement in the host's innate immune.

[Construction of the eukaryotic expression vector pEGFP-claudin-1 and its expression in 293T cells].

Aim: To construct the eukaryotic expression vector pEGFP-claudin-1 and to make it express expressed in 293T cells.

Methods: Claudin-1 ORF was amplified by reverse transcription polymerase chain reaction (RT-PCR). The eukaryotic expression vector pEGFP-claudin-1 was constructed by introducing claudin-1 DNA fragment into the sites of Xho I and BamH I of pEGFP-C3 vector.

[TLR7 protein expression induced by bacterial lipopolysaccharide in DC2.4 cells].

Aim: To investigate the role of bacterial Lipopolysaccharide (LPS) in inducing TLR7 protein expression in DC2.4 cells.

Methods: DC2.

[Isolation of exosomes derived from dendritic cells by ultrafiltration centrifugalization and their morphologic characteristics].

Aim: To investigate a method for isolating exosomes by ultrafiltration centrifugalization based on their physical size and density so as to advance traditional method and promote recovery rate.

Methods: The culture supernatant of murine dendritic cells line (DC2.4) was collected and clarified through a hollow fiber cartridge to remove cells and their debris.

Toll-like receptor 4 siRNA attenuates LPS-induced secretion of inflammatory cytokines and chemokines by macrophages.

Toll-like receptor 4 (TLR4) is critical for activation of macrophages by Lipopolysaccharide (LPS). In this study, we investigated the silencing effects of TLR4-specific 21-nt small interfering RNAs (siRNA) on TLR4 expression in RAW264.7 cells.