Specimens and clinical data were collected from 243 hand, foot and mouth disease patients in Beijing in 2013. In total, 130 stool specimens were genotyped for enterovirus. Hand, foot and mouth disease was mainly detected in suburban areas and at the edges of urban areas between May and August. Coxsackievirus (CV) A6 replaced enterovirus (EV) 71 and CVA16, becoming the main causative agent of hand, foot and mouth disease. CVA6 infection led to significantly reduced fever duration and glucose levels compared with EV71 infection.

This study was designed to investigate the role of serum GP73 for diagnosing significant fibrosis in patients with chronic hepatitis B virus (HBV) infections. Two populations were enrollment. All subjects were patients with chronic HBV infections. First population included 761 patients, who received liver stiffness measurement; the second population included 633 patients, who undertaken liver biopsy, in which 472 patients with nearly normal ALT. All patients received serum GP73 test. The effect of GP73 recombinant protein to HepG2 cells and LX2 cells were observed in vitro. Results showed that serum GP73 concentration is correlated with liver stiffness (r = 0.601). The area under ROC curve is 0.76. The sensitivity and specificity of GP73 for significant fibrosis (≥F2) diagnosis were 62.81%, 80.05% respectively (cut off: 76.6 ng/ml). Serum GP73 concentration was significantly correlated with the grading of fibrosis (r = 0.32, and 0.35, in 633 and 472 patients, respectively.) GP73 had a striking performance for diagnosing S2 in patients with chronic HBV infections. In 472 patients with nearly normal ALT, the sensitivity and specificity of GP73 for S2 diagnosis were 62.5% and 80.0% respectively, where the cut-off was set at 82 ng/ml. GP73 recombinant protein may prompt LX2 cells proliferation at the concentration 10–100 ng/ml. The present results indicated that GP73 may be a marker for diagnosing significant fibrosis in patients with chronic HBV infections, and may be a new contributor to fibrogensis.

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PurposeDiammonium glycyrrhizinate (DG) is a replacement for glycyrrhizic acid, which is used as a hepatic protector in clinical practice for most liver diseases. The potential role of immune response during autoimmune hepatitis—induced by concanavalin A (Con A)—remains to be elucidated.MethodsC57BL/6J mice were treated with two different doses of DG (75 and 200 mg/kg) 2 hrs before administering Con A. The mice were sacrificed after administering Con A for 0, 6, and 24 hrs. Liver damage grade and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin levels were evaluated. The expression level of cleaved-caspase 3 in liver was detected by Western blotting. Inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon γ (IFN-γ) in liver were detected by RT-PCR. Thymus, peripheral blood, spleen, and liver tissues were collected to analyze the percentages of NKT cells, subsets of CD4+CD25−CD69+ and CD8+CD69+ T cells, and subsets of regulatory T cells (Tregs).ResultsOur results revealed that DG pre-treatment significantly decreased the serum ALT and AST levels and improved the histological damage in Con A-induced autoimmune liver injury. Pre-treatment with DG down-regulated the inflammatory cytokines upon challenge with Con A. The DG pre-treatment inhibited the apoptosis of T lymphocytes in the thymus. Further, it effectively suppressed the proliferation of CD4+CD25−CD69+ and CD8+CD69+ subsets in the peripheral blood and spleen. In addition, the DG pretreatment significantly downregulated the frequency of NKT cells, while upregulating the frequency of Tregs in the liver.ConclusionWe believe that the potential protective effect of DG against Con A-induced hepatitis may be partially attributed to its inhibitory activities on inflammatory cytokines in the livers, lymphocyte apoptosis in the thymus, NKT cells proliferation, and activation of CD8+T cells; further, there may also be a possibility of DC promoting Tregs proliferation.

Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation in hepatocytes. Very low density lipoprotein (VLDL) is a major secretory product of the liver that transports endogenously synthesized TG. Disrupted VLDL secretion may contribute to the accumulation of TG in hepatocytes. ApoB100 (apolipoprotein B100) is a glycoprotein and an essential protein component of VLDL. Its glycosylation may affect VLDL assembly and secretion. However, which glycosyltransferase catalyzes apoB100 glycosylation is unknown. In this study, we cloned the GLT8D2 (glycosyltransferase 8 domain containing 2) gene from HepG2 cells and generated a series of plasmids for in vitro studies of its molecular functions. We discovered that GLT8D2 was localized in the ER, interacted with apoB100, and positively regulated the levels of apoB100 protein in HepG2 cells. Based on these results, we propose that GLT8D2 is a glycosyltransferase of apoB100 that regulates apoB100 levels in hepatocytes.

Hepatitis B virus (HBV), a major causative agent of hepatocellular carcinoma (HCC), encodes an oncogenic X protein (HBx) that transcriptionally activates multiple viral and cellular promoters. The present study aimed to identify the specific gene mutation related to the clinical outcome of HCC. Seventy-two HBV-infected patients (38 with chronic HBV infection and 34 with HCC) with well-characterized clinical profiles were enrolled. The HBx region was amplified from patient serum samples and analyzed by sequencing. Genotypes were determined using the National Center for Biotechnology Information genotype tool. All isolates were genotype B or C. Enhancer II nucleotide substitutions in the HCC group were significantly different from those in the chronic hepatitis B (CHB) group (Ρ < 0.05). HCC patients with genotype C had a higher risk of harboring the 1762/1764 double mutation than those with genotype B. The incidence of the 1762/1764 double mutation was higher in the high viral load group (>10(6) copies/ml) than in the low viral load group (≤10(6) copies/ml) (P = 0.03). The 1762/1764 double mutations may be related to the genotype and viral load. We found significantly more direct repeat sequence 1 (DR1) nucleotide substitutions in the HCC group (32.4%, 11/34) than in the CHB group (10.5%, 4/38) (Ρ < 0.05). Patients with higher viral load and genotype C had a higher incidence of 1762/1764 double mutations, which may not be related with development of HCC. Enhancer II and DR1 may play an important role in HCC development via nucleotide substitution.

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BackgroundRecent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver.MethodsRat model of NAFLD was established by induction with high-fat-diet. The GLT8D2 expression in rat liver was examined using immunohistochemistry. Oil Red O staining and triglyceride assay were used to measure the effect of abnormal GLT8D2 expression on lipid accumulation in HepG2 cells. The expression levels of lipid metabolism-related key molecules, namely sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-coA desaturase (SCD), carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP), in HepG2 cells with abnormal GLT8D2 expression were determined by western blot analyses.ResultsThe expression of GLT8D2 was higher in the liver of rats with NAFLD than in the control rats, and GLT8D2 was mainly located around lipid droplets in hepatocytes. GLT8D2 expression increased in steatosis HepG2 cells compared with that in normal HepG2 cells. GLT8D2 positively regulated lipid droplet accumulation and triglyceride content in HepG2 cells. Upregulation or knockdown of GLT8D2 had no effect on the expressions of SREBP-1c, SCD or CPT-1 proteins in HepG2 cells. However, GLT8D2 expression negatively regulated the expression of MTP protein in HepG2 cells.ConclusionGLT8D2 participated in NAFLD pathogenesis possibly by negatively regulating MTP expression. Specific inhibition of GLT8D2 via an antagonistic strategy could provide a potential candidate approach for treatment of NAFLD.