Glucocorticoids have been widely applied to various clinical treatment, however some serious side effects may occur during the treatment. It is widely known that glucocorticoids produce a marked effect through binding to glucocorticoid receptor (GR). As withaferin A can provide multiple health benefits, this work aims to confirm withaferin A as a potential selective GR modulator with anti-inflammatory effect. Fluorescence polarization assay confirmed that withaferin A could steadily bind to GR with an IC 50 value of 203.80 ± 0.36 μM. Meanwhile, glucocorticoid receptor translocation of withaferin A was measured by nuclear fractionation assay. Dual luciferase reporter assay showed that withaferin A did not activate GR transcription. Furthermore, withaferin A decreased the GR-related protein expression with less side effects. The result of molecular docking showed that hydrogen-bonding and hydrophobic interactions contributed to the binding of withaferin A with GR. In addition, the GR-withaferin A complex maintained a stable binding throughout the dynamics simulation process. Enzyme-linked immunosorbent assay showed that withaferin A inhibited the production of cytokines, confirming its anti-inflammatory effect. These findings indicate that withaferin A is a potential selective GR modulator and this work may provide a research basis for developing dietary supplements and nutraceuticals against inflammation.
Glassy precursors in the Li 1+ x Ga x Ge 2- x P 3 O 12 system are prepared by melting and casting. The glasses are annealed at the crystallization peak temperatures to obtain glass ceramics with Na-superionic conducting structure. The ionic conductivity can be significantly increased by substituting Ge with Ga and Li. The highest ionic conductivity of the glass ceramics is 9.74 × 10 −5 S cm −1 at 20 °C. Multiple magic angle spinning nuclear magnetic resonance (MAS NMR) techniques are used to characterize the structural transitions from glasses to their glass ceramic counterparts. 71 Ga and 31 P MAS NMR spectra have shown that the local structures of the glasses are distinctly modified after crystallization. The second coordinated shells of Ga 3+ ions are consisted of phosphorus in both glasses and glass ceramics although their coordination numbers change. The glassy precursors show homonuclear segregations such as P-O-P and Ge-O-Ge linkages. However, the glass ceramics are homogeneous, in which per phosphorus tetrahedron connects with total four Ga and Ge, forming four different phosphorus species (Q 0 (4-n)Ge, nGa (n = 0, 1, 2, and 3)). A random distribution model can be used to quantitatively predict the population of every Q 0 (4-n)Ge, nGa species, if the compositions are known. A correlation between local structure and ionic conductivity is proposed.
危险品化学品经营许可证（带存储）