Antiandrogenic, Maspin Induction, and Antiprostate Cancer Activities of Tanshinone IIA and Its Novel Derivatives with Modification in Ring A

Expression of metastatic suppressor maspin is lost in advanced prostate cancer. Clinically relevant mutations in androgen receptor (AR) convert antiandrogens into AR agonists, promoting prostate tumor growth. We discovered tanshinone IIA (TS-IIA) is a potent antagonist of mutated ARs and induces maspin expression through AR. TS-IIA suppressed AR expression and induced apoptosis in LNCaP cells. Syntheses of TS-IIA derivatives (<b>1</b>–<b>9</b>) revealed that the 4,4-dimethyl group at ring A is important for TS-IIA’s antiandrogenic and maspin induction activities

Forest plot of the association of SDF1-3’A and death stratified by sources of research subjects.

<p>Forest plot of the association of SDF1-3’A and death stratified by sources of research subjects.</p

Forest plot of the association of SDF1-3’A and HIV susceptibility in different genetic models.

<p>(A)recessive model (B) homozygous model (C) heterozygous model (D) allele model. Studies were divided into two subgroups (High NOS scores group and Low NOS scores group) as indicated.</p

Forest plot of the association of SDF1-3’A and AIDS progression according to CDC93 criteria stratified by sources of research subjects.

<p>Forest plot of the association of SDF1-3’A and AIDS progression according to CDC93 criteria stratified by sources of research subjects.</p

Forest plot of the association of SDF1-3’A and AIDS progression according to CDC87 criteria stratified by sources of research subjects.

<p>Forest plot of the association of SDF1-3’A and AIDS progression according to CDC87 criteria stratified by sources of research subjects.</p

Selection process of studies included in meta-analysis.

<p>Selection process of studies included in meta-analysis.</p

Identification of Triptophenolide from <i>Tripterygium wilfordii</i> as a Pan-antagonist of Androgen Receptor

A compound, triptophenolide, derived from <i>Tripterygium wilfordii</i> was identified as an antiandrogen. Triptophenolide inhibits the activity of both wild-type and F876L mutant androgen receptors. Triptophenolide exhibits its antiandrogenic activity through competitive binding with androgen in the hormone-binding pocket, decreasing the expression of androgen receptor, and reducing the nuclear translocation of androgen receptor

Controllable Fabrication of Noniridescent Microshaped Photonic Crystal Assemblies by Dynamic Three-Phase Contact Line Behaviors on Superhydrophobic Substrates

Enormous research efforts have been made to self-assemble monodisperse colloidal spheres into special microscopic shapes (e.g., superbeads, superballs, or doughnuts), due to their widespread applications in sensors, displays, separation processes, catalysis, etc. But realization of photonic crystal (PC) assemblies with both facile microshape control and a noniridescent property is still a tough task. Herein, we demonstrate the controllable fabrication of noniridescent microshaped PC assemblies by evaporation-induced self-assembly inside aqueous colloidal dispersion droplet templates on superhydrophobic substrates. The microshapes of the PC assemblies could be tuned from microbeads to microwells to microellipsoids by manipulating the dynamic behaviors of the three-phase contact line of the colloidal droplets during the evaporating process. Structure characterization shows that the PC assemblies are crack-free, consisting of an ordered periodic arrangement of colloidal spheres in the surface layers and amorphous inner layers. The incorporation of black Fe₃O₄ nanoparticles into the PC assembly lattice is demonstrated to endow the PC assemblies with enhanced noniridescent structural colors with wide-viewing angles and a superparamagnetic property. The crack-free noniridescent PC assemblies with controlled microshapes have promising applications in the fields of nontoxic, nonbleaching pigments and energy-efficient full-color display pixels, and their facile fabrication procedure may provide guidance for creating new types of substructured colloidal particles

Design and Synthesis of Dual-Target Inhibitors Targeting Androgen Receptors and Glucocorticoid Receptors to Overcome Antiandrogen Resistance in Castration-Resistant Prostate Cancer

Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit the activity of both AR and GR. Herein, we optimized the structure of Z19 and identified GA32 as a potent AR/GR dual inhibitor. GA32 efficiently reduced the mRNA and protein levels of AR/GR downstream genes. GA32 efficiently inhibited the proliferation of enzalutamide resistance CRPC both in vitro and in vivo. GA32 could directly bind to AR and GR, and the predicted binding modes for GA32 with AR/GR suggested that GA32 binds to the AR or GR hormone binding pocket. This work provides a potential lead compound with dual AR/GR inhibitory activity to conquer the drug resistance of CRPC

Design and Synthesis of Dual-Target Inhibitors Targeting Androgen Receptors and Glucocorticoid Receptors to Overcome Antiandrogen Resistance in Castration-Resistant Prostate Cancer

Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit the activity of both AR and GR. Herein, we optimized the structure of Z19 and identified GA32 as a potent AR/GR dual inhibitor. GA32 efficiently reduced the mRNA and protein levels of AR/GR downstream genes. GA32 efficiently inhibited the proliferation of enzalutamide resistance CRPC both in vitro and in vivo. GA32 could directly bind to AR and GR, and the predicted binding modes for GA32 with AR/GR suggested that GA32 binds to the AR or GR hormone binding pocket. This work provides a potential lead compound with dual AR/GR inhibitory activity to conquer the drug resistance of CRPC