Ahmadhaugaard1269

Resveratrol (RES) is a polyphenolic plant antitoxin that increases the level of the tumor suppressor gene deleted in liver cancer 1 (DLC1) to suppress cancer progression. Dihydroartemisinin (DHA), a main active metabolite of anti-malarial drug artemisinin (ART), inhibits cancer cell invasion and migration by decreasing the translationally controlled tumor protein (TCTP), as reported in a few literature studies. LY2157299 concentration Compelling evidence has shown that combination therapy with two or more compounds is more effective than treatment with a compound alone. However, the mechanism of combination of DHA and RES on inhibition of cancer cell migration has not been reported. In this study, our results showed that combination of DHA and RES, compared to each compound alone, synergistically inhibited migration along with the decrease of wound closures and F-actin formation in HepG2 and MDA-MB-231 cancer cells. This combination treatment up-regulated DLC1 and down-regulated TCTP expressions significantly. The two proteins were identified to colocalize in focal adhesions and form a complex. Depletion of DLC1 increased TCTP expression, and transfection with either GFP-DLC1-WT or GFP-DLC1-R718A (GAP-dead mutant) decreased the TCTP level markedly, indicating that DLC1 negatively regulated TCTP in a RhoGAP-independent manner. Furthermore, this combination treatment impeded the migration of HepG2 and MDA-MB-231 cancer cells via Cdc42 regulating JNK/NF-κB and N-WASP signaling pathways, and knockdown of DLC1 obviously increased the levels of Cdc42 and the molecules related to both signaling pathways in MDA-MB-231 cells. The combination also effectively inhibited the growth of xenograft tumors in an avian embryo model. In sum, we reveal a novel combination of DHA and RES that inhibits cancer cell migration by modulating the DLC1/TCTP axis to hinder the Cdc42 related signaling pathway. This combination treatment may be a promising therapeutic strategy to inhibit cancer cell migration by targeting DLC1 and TCTP.CaH2 has 20 times the energy density of molten salts and was patented in 2010 as a potential solar thermal energy storage material. Unfortunately, its high operating temperature (>1000 °C) and corrosivity at that temperature make it challenging to use as a thermal energy storage (TES) material in concentrating solar power (CSP) plants. To overcome these practical limitations, here we propose the thermodynamic destabilization of CaH2 with Zn metal. It is a unique approach that reduces the decomposition temperature of pure CaH2 (1100 °C at 1 bar of H2 pressure) to 597 °C at 1 bar of H2 pressure. Its new decomposition temperature is closer to the required target temperature range for TES materials used in proposed third-generation high-temperature CSP plants. A three-step dehydrogenation reaction between CaH2 and Zn (1  3 molar ratio) was identified from mass spectrometry, temperature-programmed desorption and in situ X-ray diffraction studies. Three reaction products, CaZn13, CaZn11 and CaZn5, were confirmed from in situ X-ray diffraction studies at 190 °C, 390 °C and 590 °C, respectively. The experimental enthalpy and entropy of the second hydrogen release reaction were determined by pressure composition isotherm measurements, conducted between 565 and 614 °C, as ΔHdes = 131 ± 4 kJ mol-1 H2 and ΔSdes = 151 ± 4 J K-1 mol-1 H2. Hydrogen cycling studies of CaZn11 at 580 °C showed sufficient cycling capacity with no significant sintering occurring during heating, as confirmed by scanning electron microscopy, demonstrating its great potential as a TES material for CSP applications. Finally, a cost comparison study of known destabilized CaH2 systems was carried out to assess the commercial potential.The developed ammonium salt-containing hole transporting material could passivate perovskite defects and transport holes, and exhibits better performance compared with the non-ammonium salt counterpart.An iron complex bearing the facially capping tridentate 1,4,7-triazacyclononane ligand mimics structural and functional features of alpha-ketoglutarate (α-KG) dependent enzymes, and engages in enzyme-like catalytic O2 activation coupled to α-ketoacid decarboxylation, oxygenating sulfides. This system constitutes a rare case of non-enzymatic catalytic O2 activation, cycling between FeII and FeIV(O).We report the synthesis of MoRu solid-solution alloy nanoparticles using carbonyl complexes as a precursor through thermal decomposition. Alloying Ru with an early transition metal, Mo, leads to an electronic structure change, resulting in an enhancement of the catalytic activity for the hydrogen evolution reaction, which overtook that of the Pt catalyst.

Treatment for glioblastoma (GBM) remains an unmet need in medicine. Novel therapies that address GBM complexity and heterogeneity in particular are warranted. To this end, we target 4 tumor-associated receptors at a time that span virtually all of the GBM microenvironment including bulk tumor cells, infiltrating tumor cells, neovasculature, and tumor-infiltrating cells with one pharmaceutical agent delivering a cytotoxic load.

We engineered multivalent ligand-based vector proteins termed QUAD with an ability to bind to 4 of the following GBM-associated receptors IL-13RA2, EphA2, EphA3, and EphB2. We conjugated QUAD with a modified bacterial toxin PE38QQR and tested it in vitro and in vivo.

The QUAD variants preserved functional characteristics of the respective ligands for the 4 receptors. The QUAD 3.0 variant conjugate was highly cytotoxic to GBM cells, but it was nontoxic in mice, and the conjugate exhibited strong antitumor effect in a dog with spontaneous GBM.

The QUAD addresses, to a large extent, the issues of intra- and intertumoral heterogeneity and, at the same time, it targets several pathophysiologically important tumor compartments in GBM through multiple receptors overexpressed in tumors allowing for what we call "molecular resection." QUAD-based targeted agents warrant further pre- and clinical development.

The QUAD addresses, to a large extent, the issues of intra- and intertumoral heterogeneity and, at the same time, it targets several pathophysiologically important tumor compartments in GBM through multiple receptors overexpressed in tumors allowing for what we call "molecular resection." QUAD-based targeted agents warrant further pre- and clinical development.