BackgroundVitamin D is required to maintain the integrity of the intestinal barrier and inhibits inflammatory signaling pathways.ObjectiveVitamin D deficiency might be involved in cirrhosis-associated systemic inflammation and risk of hepatic decompensation in patients with liver cirrhosis.MethodsOutpatients of the Hepatology Unit of the University Hospital Frankfurt with advanced liver fibrosis and cirrhosis were prospectively enrolled. 25-hydroxyvitamin D (25(OH)D3) serum concentrations were quantified and associated with markers of systemic inflammation / intestinal bacterial translocation and hepatic decompensation.ResultsA total of 338 patients with advanced liver fibrosis or cirrhosis were included. Of those, 51 patients (15%) were hospitalized due to hepatic decompensation during follow-up. Overall, 72 patients (21%) had severe vitamin D deficiency. However, patients receiving vitamin D supplements had significantly higher 25(OH)D3 serum levels compared to patients without supplements (37 ng/mL vs. 16 ng/ml, P<0.0001). Uni- and multivariate analyses revealed an independent association of severe vitamin D deficiency with the risk of hepatic decompensation during follow-up (multivariate P = 0.012; OR = 3.25, 95% CI = 1.30–8.2), together with MELD score, low hemoglobin concentration, low coffee consumption, and presence of diabetes. Of note, serum levels of C-reactive protein, IL-6 and soluble CD14 were significantly higher in patients with versus without severe vitamin D deficiency, and serum levels of soluble CD14 levels declined in patients with de novo supplementation of vitamin D (median 2.15 vs. 1.87 ng/mL, P = 0.002).ConclusionsIn this prospective cohort study, baseline vitamin D levels were inversely associated with liver-cirrhosis related systemic inflammation and the risk of hepatic decompensation.
Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.
BackgroundDespite the wide use of implants in dentistry, there is insufficient information about the ideal cement for retention.PurposeTo determine the cement bond strength and marginal leakage of crown and partial denture cemented to implant abutments by four different types of cement.Materials and MethodsEighty‐four direct abutments were divided into eight groups (n = 7). Fifty‐six crown and bridge restorations were cemented using zinc phosphate (ZM), temporary cement (TM), resin‐modified glass‐ionomer cement (GM), and self‐adhesive resin cement (RM). After cementation, thermal cycling and incubation in basic fuchsin dye was applied. The maximum load to failure, marginal leakage, and fracture modes were evaluated.ResultsThe mean of retention strength for the bridges (874 N) was higher than the crown samples (705 N) (P = .005). The mean of retention strength for each cement group was ZM = 1298, RM = 1027, GM = 646, and TM = 187 N (P ≤ .0001). Marginal leakage was recorded in majority of the samples; the highest incidence was detected for ZM samples. The cement fracture was mostly adhesive in nature.ConclusionSelf‐adhesive resin and resin‐modified glass ionomer cement had better mechanical properties to retain implant supported restorations.
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