Chemical-genetic screen identifies riluzole as an enhancer of Wnt/β-catenin signaling in melanoma

To identify new protein and pharmacological regulators of Wnt/β-catenin signaling, we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the β-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in?vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance β-catenin signaling. The unexpected regulation of β-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug.     

Chemical composition and bioactivities of the marine alga Isochrysis galbana from Taiwan

The present study investigated the chemical composition of Isochrysis galbana Parke, a marine microalga which is widely used as a feedstock in aquaculture. From gas chromatography/mass spectrometric analysis the mono-sugar compositions of I. galbana were 2.1% fucose, 2.5% rhamnose, 2.7% arabinose, 8.5% xylose, 15.7% mannose, 32.7% galactose and 35.8% glucose. The polysaccharides of I. galbana were able to induce prointerleukin-1beta (pro-IL-1beta) protein expression within murine macrophages. Furthermore, five kinds of chlorophyll and one sterol were separated from the ethanolic extracts, including pheophorbide-a, ethyl pheophorbide-a, 10S-10-hydroxypheophytin-a, 10R-10-hydroxypheophytin-a, (132-R)-pheophytin-a, and brassicasterol. In addition, the major soluble components of the ethanol/n-hexane extract were 9-octadecenoic acid (E) (38.4%), hexadecanoic acid (23.3%), tetradecanoic acid (15.7%), and octadecanoic acid (7.2%), but only a few polyunsaturated fatty acids were found, such as 9,12,15-octadecatrienoic acid (1.9%), 9,12-octadecadienoic acid (Z,Z) (3.4%), and docosahexaenoic acid (0.2%). This is the first occasion that polysaccharides from I. galbana have been demonstrated to exert immunomodulatory properties by the induction of IL-1 within macrophages.     

Effects of carbon nanotubes on dynamic mechanical property,thermal property,and crystal structure of poly(L‐lactic acid)

Effects of carbon nanotubes (CNT) on the dynamic mechanical property, thermal property, and crystal structure of poly(L ‐lactic acid) (PLLA) were investigated. Dynamic mechanical analysis (DMA) found that CNT via grafting modification with PLLA (CNT‐g‐PLLA) could result in effective reinforcing effects. Tan δ of DMA found that CNT‐g‐PLLA was compatible with the PLLA matrix, giving a single T_g of the composite with a higher CNT‐g‐PLLA loading giving a higher T_g of the composite. Wide angle X‐ray diffraction (WAXD) data demonstrated that CNT could assist the disorder‐to‐order (α′‐to‐α) transition in PLLA crystals but did not lead to a more compact chain packing of the crystal lattice in PLLA composites than in pure PLLA. The equilibrium melting temperature (T) obtained from Hoffman‐Weeks plots were found to increase with increasing CNT‐g‐PLLA content. Small angle X‐ray scattering data revealed that thicknesses of crystal layer and amorphous layer of PLLA both decreased with increasing CNT contents. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 145–152, 2010     

Determination of Allosteric Effects and Interstrand Bidentate Interactions in DNA‐Peptide Molecular Recognition

To study DNA allostery, quantitative DNase I footprinting studies were carried out on a newly designed peptide His‐Hyp‐Lys‐Lys‐(Py)₄‐Lys‐Lys‐NH₂ (HypKK‐10) containing the XHypKK (Hyp = hydroxyproline) and polyamide motifs. The interconnection of DNA footprints of peptides HypKK‐10 and the parent peptide PyPro‐12 supports the proposal that interaction network cooperativity is preferred in DNA‐peptide interactions between multiple recognition sites. A simple method of determining interstrand bidentate interactions between the peptide moieties and DNA bases is introduced. It is envisaged that interstrand bidentate interactions also participate in the relay of conformational changes to recognition sites on the complementary strands. Circular dichroism studies of the titration of peptide HypKK‐10 with an oligonucleotide duplex indicate that this peptide binds in a dimeric fashion to DNA in the minor groove. This work may prompt the design of new DNA binding ligands for the study of DNA‐peptide allosteric interactions and DNA interaction network.     

Hard nanocomposite comprising stereoregular syndiotactic polypropylene with chemically bonded gold nanoparticles

An effective method to synthesize directly a hard composite material containing uniformly dispersed nanogold particles chemically bonded with a stereospecific, crystalline polymer matrix has been developed. Syndiotactic polypropylene was synthesized and functionalized to have a hydroxyl terminal group (sPP_OH) via a metallocene catalysis with a selective chain transfer. Next, sPP_OH was activated to react with ethylene sulfide forming the thiol‐terminated polymer, sPP_SH. sPP_SH was then chemically bonded to gold nanoparticles (AuNPs) formed in situ via a reduction of HAuCl₄. The bonding between thiol and AuNP stabilized the AuNPs and led to the formation of sPP_AuNPs composite containing uniformly‐dispersed AuNPs of a 19–40 nm size without noticeable aggregation. Furthermore, the chemical bonding of AuNPs has afforded sPP_AuNPs a thermal degradation temperature (T_D) 49.4 °C higher than the pristine sPP or sPP_OH and 25.7 °C higher than sPP_SH without any adverse effect on the crystalline temperature and melting temperature. In addition, the characteristic UV‐Vis absorption wavelength of sPP_AuNPs remains the same at various temperatures, thus indicating the independence of optical property on temperature as well as the good thermal stability of the sPP_AuNPs composite. ¹H NMR, ¹³C NMR, FESEM, STEM, XPS, TGA and DSC were used to investigate the molecular structure, morphology and thermal properties of the resulting sPP_AuNPs nanocomposite. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Rhodamine‐Ethylenediol,A Novel Vital Fluorescent Probe for Labelling Alkaline Phosphatase‐Rich Organelles

Zebrafish have received considerable attention as an organism‐based model in the development of pharmacological agents.^1,2 Many small molecules applied to zebrafish show important behaviours and may constitute new kinds of markers for clinical purposes.³ Analysis of these molecules can facilitate the development of useful tools for monitoring environmental changes.⁴ Many chemicals that are toxic to the environment are known to influence the sensory systems of humans⁵ and fish.⁶ One important sensory system in all fish is the lateral line organ,⁷ which is readily accessible for the assessment of environmental changes.⁸ Neuromasts, which are located on the surface of the fish body, are one of the major components of the lateral lines of the zebrafish.⁹ Copper‐enriched water is known to affect the olfactory system in fish. Therefore, small molecules that induce specific patterns in the neuromasts of zebrafish should provide an important animal model with which to explore the effects of environmental changes on the sensory system.^10,11 Recently, chemical sensors based on the rhodamine skeleton¹² have been designed to specifically detect metal ions, such as Cu(II)¹³ and Fe(III)/Hg(II),¹⁴ in zebrafish. However, there has been no report of these rhodamine derivatives used in the specific recognition of the sensory system of zebrafish. Commonly, the sensory system is studied with antibody staining assays of scarified fish. Here, we report that a new rhodamine derivative can be used as a fluorescent chemical probe to visualize the neuromasts and intestinal villi of living zebrafish. Based on the specific recognition of this area in zebrafish, we narrowed the possible enzymes targeted by this rhodamine probe to alkaline phosphatase and confirmed this with a binding assay. It is a well‐recognized challenge to develop a fluorescent chemical probe that specifically recognizes a particular enzyme. Furthermore, the transfer of phosphate groups to certain enzymes can activate their catalytic reactivity, triggering a cascade reaction in a signal transduction pathway. The alkaline‐phosphatase‐specific recognition by this rhodamine derivative may be applicable to clinical purposes.     

Four new podocarpane-type trinorditerpenes from the bark of Taiwania cryptomerioides

Further studies on the bark of Taiwania cryptomerioides found four new podocarpane derivatives, 1beta,13-dihydroxy-8,11,13-podocarpatriene (1), 14,18-dihydroxy-13-methoxy-8,11,13-podocarpatriene (2), 1beta,14-dihydroxy-13-methoxy-8,11,13-podocarpatriene-2,7-dione (3), and 3beta,14-dihydroxy-13-methoxy-8,11,13-podocarpatrien-7-one (4), together with a known 1beta,13,14-trihydroxy-8,11,13-podocarpatrien-7-one (5). Those structures were elucidated principally from spectral evidence.     

Hydrogenation of olefins in supercritical CO(2) catalyzed by palladium nanoparticles in a water-in-CO(2) microemulsion

Nanometer-sized metallic palladium particles can be synthesized by hydrogen reduction of Pd2+ ions dissolved in the water core of a water-in-CO2 microemulsion. The Pd nanoparticles, stabilized by the micromeulsion and uniformly dispersed in the supercritical fluid phase, are effective catalysts for hydrogenation of olefins. Examples of rapid and efficient hydrogenation of water-soluble and CO2-soluble olefins catalyzed by the Pd nanoparticles in supercritical CO2 are given.