miR-194 Up-Regulates Cholesterol 7 Alpha-Hydroxylase Expression via ß-Catenin Signaling and Aggravates Cholestatic Liver Diseases.

miR-194 is abundantly expressed in hepatocytes, and its depletion increases hepatic resistance to acetaminophen-induced acute injuries. In this study, the biological role of miR-194 in cholestatic liver injury was investigated by using miR-194/miR-192 cluster liver-specific knockout (LKO) mice, in which no liver injuries or metabolic disorders were predisposed. Bile duct ligation (BDL) and 1-naphthyl isothiocyanate (ANIT) were applied to LKO and matched control wild-type (WT) mice to induce hepatic cholestasis. Periportal liver damage, mortality rate, and liver injury biomarkers in LKO mice were significantly less than in WT mice after BDL and ANIT injection. Intrahepatic bile acid level was significantly lower in the LKO liver within 48 hours of BDL- and ANIT-induced cholestasis compared with WT. Western blot analysis showed that ß-catenin (CTNNB1) signaling and genes involved in cellular proliferation were activated in BDL- and ANIT-treated mice. The expression levels of cholesterol 7 alpha-hydroxylase (CYP7A1), pivotal in bile synthesis, and its upstream regulator hepatocyte nuclear factor 4α were reduced in primary LKO hepatocytes and liver tissues compared with WT. The knockdown of miR-194 using miRNA inhibitors reduced CYP7A1 expression in WT hepatocytes. In contrast, the knockdown of CTNNB1 and overexpression of miR-194, but not miR-192, in LKO hepatocytes and AML12 cells increased CYP7A1 expression. In conclusion, the results suggest that the loss of miR-194 ameliorates cholestatic liver injury and may suppress CYP7A1 expression via activation of CTNNB1 signaling.

Electrochemical fabrication of nickel phosphide/reduced graphene oxide/nickel oxide composite on nickel foam as a high performance electrode for supercapacitors.

Three-dimensional (3D) nickel phosphide/reduced graphene oxide (rGO)/nickel oxide composite on nickel foam (Ni2P/rGO/NiO/NF) is fabricated as a supercapacitor (SC) electrode material via the two-step electrochemical deposition of graphene oxide (GO) and nickel phosphide on the nickel foam. Typically, rGO/NiO/NF is fabricated at first by the electrochemical treatment of nickel foam at 10 V in 0.1 M sulfuric acid with GO for 10 min. The result reveals that NiO nanosheets are vertically grown on the surface of nickel foam and rGO is deposited on the surface of NiO/NF, leading to the enhancement of capacity. Secondly, nickel phosphide is electrochemically deposited on the surface of rGO/NiO/NF in the sodium hypophosphite-based aqueous solution at 10 mA cm-2 to yield the Ni2P/rGO/NiO/NF. The deposition of Ni2P leads to a much higher capacity. The optimal areal and mass specific capacities are obtained as 3.59 C cm-2 and 742 C g-1 at the electrochemical deposition time of 30 and 10 min, respectively. The high capacity reveals that the proposed two-step electrochemical fabrication process is facile and effective. In addition, the Ni2P/rGO/NiO/NF electrode-based all-solid-state asymmetric SC was fabricated and could successfully turn on a light-emitting diode light. This revealed its feasibility in practical application and confirmed that the resulting 3D Ni2P/rGO/NiO/NF has a great potential as the SC electrode material.