catena-Poly[[aqua­bis­(N 6-benzyl­adenine-κN 3)copper(II)]-μ-benzene-1,4-dicarboxyl­ato-κ2 O 1:O 4]

In the title compound, [Cu(C8H4O4)(C12H11N5)2(H2O)]n, the CuII ion is five-coordinated by two carboxyl­ate O atoms from two symmetry-related benzene-1,4-dicarboxyl­ate ligands, two N atoms from two symmetry-related N 6-benzyl­adenine ligands and one water O atom in a square-pyramidal environment. The CuII and water O atoms lie on a twofold rotation axis, and the benzene-1,4-dicarboxyl­ate ligand lies on an inversion center. The water O atom occupies the apical position and the basal plane is occupied by two O atoms and two N atoms. Each benzene-1,4-dicarboxyl­ate anion acts as a bis-monodentate ligand that binds two CuII cations, forming an infinite chain extending parallel to [001]. The N 6-benzyl­adenine ligands are attached on both sides of the chain. Neighboring chains are further inter­connected into the resulting three-dimensional supra­molecular architecture via O—H⋯O, N—H⋯O and N—H⋯N hydrogen bonds

Tissue specific induction of p62/sqstm1 by farnesoid X receptor

Background: Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily and is a ligand-activated transcription factor essential for maintaining liver and intestinal homeostasis. FXR is protective against carcinogenesis and inflammation in liver and intestine as demonstrated by the development of inflammation and tumors in the liver and intestine of FXR knock-out mice. However, mechanisms for the protective effects of FXR are not completely understood. This study reports a novel role of FXR in regulating expression of Sqstm1, which encodes for p62 protein. p62 plays an important role in maintaining cellular homeostasis through selective autophagy and activating signal transduction pathways, such as NF-κB to support cell survival and caspase-8 to initiate apoptosis. FXR regulation of Sqstm1 may serve as a protective mechanism. Methods and Results: This study showed that FXR bound to the Sqstm1 gene in both mouse livers and ileums as determined by chromatin immunoprecipitation. In addition, FXR activation enhanced transcriptional activation of Sqstm1 in vitro. However, wild-type mice treated with GW4064, a synthetic FXR ligand, showed that FXR activation induced mRNA and protein expression of Sqstm1/p62 in ileum, but not in liver. Interestingly, FXR-transgenic mice showed induced mRNA expression of Sqstm1 in both liver and ileum compared to wild-type mice. Conclusions: Our current study has identified a novel role of FXR in regulating the expression of p62, a key factor in protein degradation and cell signaling. Regulation of p62 by FXR indicates tissue-specific and gene-dosage effects. Furthermore, FXR-mediated induction of p62 may implicate a protective mechanism of FXR. © 2012 Williams et al

Novel potential therapeutic targets of alopecia areata

Alopecia areata (AA) is a non-scarring hair loss disorder caused by autoimmunity. The immune collapse of the hair follicle, where interferon-gamma (IFN-γ) and CD8+ T cells accumulate, is a key factor in AA. However, the exact functional mechanism remains unclear. Therefore, AA treatment has poor efficacy maintenance and high relapse rate after drug withdrawal. Recent studies show that immune-related cells and molecules affect AA. These cells communicate through autocrine and paracrine signals. Various cytokines, chemokines and growth factors mediate this crosstalk. In addition, adipose-derived stem cells (ADSCs), gut microbiota, hair follicle melanocytes, non-coding RNAs and specific regulatory factors have crucial roles in intercellular communication without a clear cause, suggesting potential new targets for AA therapy. This review discusses the latest research on the possible pathogenesis and therapeutic targets of AA