P‑Arylation of Dialkyl Phosphites and Secondary Phosphine Oxides with Arynes

The novel P-arylation of dialkyl phosphites and secondary phosphine oxides with arynes has been achieved. The reactions produce dialkyl arylphosphonates in 71–99% yield and tertiary phosphine oxides in 68–92% yield under mild conditions

α‑Glucosidase Inhibition and Antihyperglycemic Activity of Phenolics from the Flowers of Edgeworthia gardneri

The flowers of Edgeworthia gardneri are consumed as an herbal tea in Tibet with potential health benefits. To complement the current knowledge regarding the chemical composition and antihyperglycemic activity of the flower of E. gardneri, two new phenolics, gardnerol A and B (<b>1</b> and <b>2</b>), along with 19 known phenolics were isolated from the flower of E. gardneri. All isolates were evaluated for their inhibitory activity against α-glucosidase. Compound <b>5</b>, identified as the major constituent of the flower of E. gardneri, showed a significant α-glucosidase inhibitory activity and acted as a competitive inhibitor. The oral administration of compound <b>5</b> at a dose of 300 mg/kg significantly reduced the postprandial blood glucose levels of normal and streptozotocin (STZ)-induced diabetic mice. Furthermore, compound <b>5</b> significantly decreased the fasting blood glucose levels in STZ-induced diabetic mice

Three-dimensional prostate tumor model based on a hyaluronic acid-alginate hydrogel for evaluation of anti-cancer drug efficacy

<p><i>In vitro</i> cell-based assays are widely applied to evaluate anti-cancer drug efficacy. However, the conventional approaches are mostly based on two-dimensional (2D) culture systems, making it difficult to recapitulate the <i>in vivo</i> tumor scenario because of spatial limitations. Here, we develop an <i>in vitro</i> three-dimensional (3D) prostate tumor model based on a hyaluronic acid (HA)-alginate hybrid hydrogel to bridge the gap between <i>in vitro</i> and <i>in vivo</i> anticancer drug evaluations. <i>In situ</i> encapsulation of PCa cells was achieved by mixing HA and alginate aqueous solutions in the presence of cells and then crosslinking with calcium ions. Unlike in 2D culture, cells were found to aggregate into spheroids in a 3D matrix. The expression of epithelial to mesenchyme transition (EMT) biomarkers was found to be largely enhanced, indicating an increased invasion and metastasis potential in the hydrogel matrix. A significant up-regulation of proangiogenic growth factors (IL-8, VEGF) and matrix metalloproteinases (MMPs) was observed in 3D-cultured PCa cells. The results of anti-cancer drug evaluation suggested a higher drug tolerance within the 3D tumor model compared to conventional 2D-cultured cells. Finally, we found that the drug effect within the <i>in vitro</i> 3D cancer model based on HA-alginate matrix exhibited better predictability for <i>in vivo</i> drug efficacy.</p

Distribution and diversity of twelve <i>Curcuma</i> species in China

<p>Genus <i>Curcuma</i> a wild species presents an important source of valuable characters for improving the cultivated <i>Curcuma</i> varieties. Based on the collected germplasms, herbariums, field surveys and other literatures, the ecogeographical diversity of Genus <i>Curcuma</i> and its potential distributions under the present and future climate are analysed by DIVA-GIS. The results indicate Genus <i>Curcuma</i> is distributed over 17 provinces in China, and particularly abundant in Guangxi and Guangdong provinces. The simulated current distributions are close to the actual distribution regions. In the future climate, the suitable areas for four <i>Curcuma</i> species will be extended, while for other three species the regions will be significantly decreased, and thus these valuable resources need protecting.</p

Effects of α-tomatine and curcumin alone or in combination on the growth of PC-3 xenograft tumors and body weight of SCID mice.

<p>Male SCID mice were injected subcutaneously with PC-3 cells (2 × 10⁶ cells/0.1 ml) suspended in 50% Matrigel in RPMI medium. After about 4 weeks, mice with PC-3 xenograft tumors (0.6–1.0 cm wide and 0.6–1.0 cm long) were i.p injected with vehicle, α-tomatine (5 mg/kg body weight), curcumin (5 mg/kg body weight), and a combination of α-tomatine (5 mg/kg body weight) and curcumin (5 mg/kg body weight) once every three day for 30 days. Immunohistochemical staining of PCNA was done to determine the effect of the various treatments on tumor cell proliferation. (A) Tumor size was expressed as percent of initial tumor size. (B) The weight (g) of each tumor was measured at the end of the experiment in mice after sacrifice. (C) Body weight was expressed as percent of initial body weight. (D) Percentage of PCNA positive cells in tumors from animals treated with vehicle, α-tomatine, curcumin or the combination of α-tomatine and curcumin. Representative micrographs of PCNA immunohistochemical staining in tumors from the control group (E), the α-tomatine-treated group (F), the curcumin-treated group (G) and the combination-treated group (H) are shown. Black arrows indicate positive PCNA staining and white arrows indicate negative PCNA staining.</p

Effects of α-tomatine and curcumin alone or in combination on the growth of cultured prostate cancer cells.

<p>Human prostate cancer cells (LNCaP, VCaP and PC-3) and non-tumorigenic prostate epithelial cells (RWPE-1) were seeded at a density of 0.2 × 10⁵ cells/ml in 35 mm tissue culture dishes and incubated for 24 h. The cells were then treated with various concentrations of α-tomatine and curcumin alone or in combination for 72 h. Viable cells was determined by the trypan blue exclusion assay. (A) Percent cell viability in the various cell lines treated with α-tomatine. (B) Percent cell viability in the various cell lines treated with curcumin. (C) Percent cell viability in the various cell lines treated with α-tomatine (1 μM) and curcumin (5 μM) alone or in combination. Each value represents mean ± S.E from three separate experiments.</p

Effect of α-tomatine and curcumin on apoptosis of cultured prostate cancer cells.

<p>LNCaP, VCaP, PC-3 and RWPE-1 cells were seeded at a density of 0.2 × 10⁵ cells/ml and incubated for 24 h. The cells were then treated with α-tomatine (α-T; 1 μM) or curcumin (Cur; 5 or 10 μM) alone or in combination for 48 h. Apoptosis was determined by morphological assessment. Each value is the mean ± S.E from three experiments.</p><p>Effect of α-tomatine and curcumin on apoptosis of cultured prostate cancer cells.</p

Effect of α-tomatine and curcumin on the level of Bcl-2, phospho-Akt and phospho-ERK1/2 in PC-3 cells.

<p>The cells were seeded at a density of 1×10⁵ cells/ml of medium in 100 mm culture dishes and incubated for 24 h. The cells were then treated with α-tomatine or curcumin alone and in combination for 24 h (for analysis of phosphor-Akt and phosphor-ERK1/2) and 48 h (for analysis of Bcl-2). The levels of Bcl-2, phospho-Akt and phospho-ERK1/2 were determined by the Western blot analysis. The band density was measured and normalized for actin.</p

Inhibitory effect of α-tomatine and curcumin alone or in combination on NF-κB activation in PC-3 cells.

<p>PC-3/N cells were seeded at a density of 0.2×10⁵ cells/ml of medium in 12-well plates and incubated for 24 h. The cells were then treated with α-tomatine alone or in combination with curcumin for 24 h. The NF-κB transcriptional activity was measured by a luciferase activity assay. Each value represents mean ± S.E from three separate experiments.</p

Structures of α-tomatine and curcumin.

<p>Structures of α-tomatine and curcumin.</p