Plasma sphingolipids: potential biomarkers for severe hepatic fibrosis in chronic hepatitis C.

The plasma profile of sphingolipids in hepatic fibrosis patients with chronic hepatitis C (CHC) is rarely considered at present. The association between plasma sphingolipids and severe fibrosis in CHC remains an obscure area of research. The aim of the present study was to assess the plasma profile of sphingolipids and to examine the association between plasma sphingolipids and severe fibrosis in CHC, in order to identify potential novel markers of severe fibrosis in CHC. A cohort of 120 treatment-naïve patients with CHC were included in the present study. Liver biopsies were performed and routine serological indicators were measured. Plasma sphingolipids were detected using high performance liquid chromatography tandem mass spectrometry. A total of 44 plasma sphingolipids were detected. Plasma hexosylceramide (HexCer; d18:1/12:0), HexCer (d18:1/16:0) and HexCer (d18:1/22:0) were shown to be significantly different in patients with CHC between those with and without severe fibrosis (Metavir F ≥ 3; P < 0.05). HexCer (d18:1/12:0) was observed to be closely associated with severe fibrosis in CHC [odds ratio (OR)=1.03] following adjustment for confounding variables in a multivariate analysis. HexCer (d18:1/12:0) had diagnostic value for severe fibrosis in CHC [area under the curve (AUC)=0.69]. In patients with CHC who had developed significant fibrosis (Metavir F ≥ 2), HexCer (d18:1/12:0) remained closely associated with severe fibrosis (OR=1.08) in this subgroup. In addition, HexCer (d18:1/12:0) had sufficient diagnostic ability (AUC=0.73) to distinguish severe fibrosis in patients with CHC with significant fibrosis. In conclusion, the present study indicated that plasma HexCer (d18:1/12:0) exhibits a close correlation with severe hepatic fibrosis in CHC, particularly in patients who have significant fibrosis. Additionally, HexCer (d18:1/12:0) may be a potential marker of severe hepatic fibrosis in CHC.

Plasma sphingolipids as potential indicators of hepatic necroinflammation in patients with chronic hepatitis C and normal alanine aminotransferase level.

Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00-1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01-1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.

[Synthesis, crystal structure and luminescent properties of a dysprosium coordinaation polymer based on pyridine-2, 6-dicarboxylic acid].

2-D layered Dy coordination polymer [Dy(PDA) (HPDA)I]n (1)(H2PDA = pyridine-2,6-dicarboxylic acid) with (4.8(2)) topological network was synthesized under hydrothermal conditions and was characterized by elemental analysis, IR spectrum, and single-crystal X-ray diffraction. X-ray diffraction analysis reveals that compound 1 is monoclinic, space group P2(1)/c. In the structure of compound 1, metal-centered Dy is connected via O atoms of H2PDA ligands to form a (4.82) topology network. The 3-D supramolecular structure of 1 is constructed through pi--pi stacking interactions between the adjacent layers. The luminescence properties of 1 were determined by UV-Vis and fluorescence spectrum in solid state at room temperature. The H2PDA and 1 exhibit the similar broad maximum absorption peak at 280 nm, which are attributed to ligand-centered pi--pi* transition. The fluorescence emission band based on ligand-center and characteristic emission of Dy3+ at the same maximum excitation wavelength of 280 nm were observed in 1. The fluorescence decay curve of complex 1 indicated that the processes of decay consists of two components, of which corresponding lifetimes tau1 = 3.61 micros and tau2 = 12.81 micros.

[Establish a transgenic mice model harboring structural genes of hepatitis C virus].

OBJECTIVES: To establish an animal model of HCV transgenic mice to elucidate the pathogenesis of hepatitis C virus infection and function of the viral structural proteins. METHODS: Structural gene of HCV were amplified and recombined into eukaryotic expression vectors, pcDNA4HisMax and pMT/BiP/V5-His A, after their expressive activity was confirmed to detect the structural protein in the transfected COS7 and S2 cells by Western blot. The fertilized expression element, which contained CMV or pMT promoter, structural gene of HCV and polyadenylation signal sequence, was microinjected into 1736 C57BL/6 mouse fertilized ova. The ova were then replanted into the oviducts of 69 pseudopregnant recipient mice. RESULTS: Twenty-five recipient mice were impregnated and later produced 105 newborns; 49 of them died from unknown causes and 57 survived. After the specific HCV structural genes were identified by PCR and Southern blot hybridization, 26 founders were obtained; among them 10 were stable expression mice and 16 were the inducible ones. The rate of founders developed from implanted embryos was only 1.50%. Through hybridization with normal mice, 58 hybrid mice have been obtained at present. CONCLUSION: Two kinds of different transgenic mice of HCV were developed; one is of stable expression, and the other is inducible. This transgenic mice model may create an opportunity for studying the function of the structural gene of HCV and elucidate its pathogenicity.