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Summary New onset diabetes mellitus (NODM) postliver transplantation (LT) is very common and may negatively affect patient and graft survival, but its causative mechanism is still unclear. This study was to analyze the connection between Hepatitis C virus (HCV) infection and NODM after LT by systematically reviewing published medical literature. We electronically searched databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to January 2008. Only retrospective studies could be identified. Seven of them were subjected to the meta‐analysis. Analysis was performed by using revman 4.2 software. We found that HCV increased the prevalence of NODM [OR 2.46; 95%CI (1.44, 4.19)]. Then, we further analyzed the association between HCV and persistent‐NODM (P‐NODM) after LT. The result showed that prevalence of P‐NODM was higher in HCV‐positive group than in HCV‐negative group with marginally statistical significance [OR = 1.39; 95%CI (1.06, 1.83)]. The present meta‐analysis based on retrospective studies suggested a significant relationship between HCV and NODM after LT, and it seems that HCV infection might also increase the prevalence of P‐NODM. Multicenter, large sized prospective studies are still needed to further confirm these results.

BackgroundIt was reported that microRNA-21(miR-21) was differentially expressed in the keratinocytes of psoriasis patients, and it may influence the apoptosis and proliferation of cells. The role of lncRNA maternally expressed gene3 (MEG3), a competing endogenous RNAs of miR-21, in the progression of psoriasis remains unclear. We aimed to unfold the influence of MEG3 and miR-21 on the proliferation and apoptosis of psoriasis epidermal cells.Methods50μg/L TNF-α was used to treat HaCaTs and NHEKs cells for 24 h, and then different experiments were conducted. qRT-PCR were applied for measuring the mRNA level of MEG3, miR-2, and caspase-8, and the protein expression of caspase-8 was measured with western blotting. Flow cytometry was used for assessing apoptosis. Cell proliferation was detected using MTT and colony formation assays. Dual luciferase reporter assay was applied for confirming the binding site between MEG3 and miR-21, miR-21 and Caspase-8.ResultsA cell model for in vitro studying the role of MEG3 in psoriasis pathophysiology was established using HaCaT and HHEKs. MEG3 was significantly down-regulated in HaCaT, HHEKs, and psoriatic skin samples. MEG3 inhibits proliferation and promotes apoptosis of Activated-HaCaT (Act-HaCaT) and Activated-HHEKs (Act- HHEK) by regulating miR-21, and the binding site between MEG3 and miR-21 was identified. We also found that miR-21 could inhibit the level of caspase-8 and identified the binding site between caspase-8 and miR-21. Some down-stream proteins of caspase-8, Cleaved caspase-8, cytc, and apaf-1 were regulated by miR-21 and MEG3.ConclusionMEG3/miR-21 axis may regulate the expression of caspase-8, and further influence the proliferation and apoptosis of psoriasis keratinocyte, Act-HaCaT and Act- HHEK. Therefore, our findings may provide a new thought for the study of pathogenesis and treatment of psoriasis.

Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis. When we analyzed template-DNA strand segregation in trypsin-dissociated human psoriatic keratinocytes using BrdU pulse-chase labeling, we found that the percentage of asymmetric segregation of BrdU was significantly increased in the cell pairs of psoriatic epidermal cells compared with normal epidermal cells. Furthermore, we also examined the effects of both interleukin (IL)-17A and IL-22 cytokines on the differentiation status of cultured human keratinocytes. The results indicated that both cytokines had synergistic effects on passage-one epidermal cell sheets derived from skin explants and also on cultured keratinocytes, were involved in the maintenance of the undifferentiated stem cell phenotype, and these results suggest an efficient mechanism for preventing the premature loss of basal stem-cell pools in the pro-inflammatory cytokine-enriched milieu of the psoriatic epidermis. Our findings suggest that inhibition of hyperactive stem cells represents a potential therapeutic target to combat recalcitrant epidermal hyperplasia in psoriasis.

The cytotoxicity and antioxidant activity on human hepatoma cell line HepG2 of three flavonoids homogenous compounds from tartary buckwheat seeds and bran, namely quercetin, isoquercetin, and rutin, were investigated. The total antioxidant competency detection results indicated that the antioxidant capacity of quercetin was the strongest in a biological response system. A [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay showed that quercetin exhibited the strongest cytotoxic effects against the HepG2 cell line. Flow cytometric analysis indicated that quercetin significantly increased the production of reactive oxygen species, and led to the G 2 /M phase arrest accompanied by an increase of apoptotic cell death after 48 h of incubation. Quercetin-induced cell apoptosis was shown to involve p53 and p21 up-regulation, Cyclin D1, Cdk2, and Cdk7 down-regulation. These results suggested that the induction of G 2 /M arrest, apoptosis, and cell death by quercetin may associate with increased expression of p53 and p21, decrease of Cyclin D1, Cdk2, and Cdk7 levels, and generation of reactive oxygen species in cells. This study will help to better understand and fully utilize medicinal resources of plant flavonoids.