A Multitarget Approach to Evaluate the Efficacy of Aquilaria sinensis Flower Extract against Metabolic Syndrome

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 µg/mL, AF caused 12.2-fold activation of PPARα and 5.7-fold activation of PPARγ, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 μg/mL. It was concluded that AF acted as a PPARα/γ dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPARα/γ dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome.     

Synthesis and spectral properties of 5-methylthio-4H-1-(p-substituted-phenyl)-3a-(p-substituted-phenyl)-9-[(m-; and p-substituted)-phenoxy]-3a,4-dihydro[1,2,4]oxadiazolo[4,5-a][1,5]benzodiazepines

The preparation of eight novel substituted [1,2,4]oxadiazolo[4,5-a][1,5]benzodiazepines which have potentially useful pharmacological properties; by 1,3-cycloaddition of benzonitrile oxides, generated in situ from benzohydroxamoyl chloride and triethylamine, to 1,5-benzodiazepine derivatives is described. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and ms.     

Engineering Protein Venoms as Self-Assembling CXCR4-Targeted Cytotoxic Nanoparticles

Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4⁺ tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4⁺ cancers.     

Calixarene-Based Copper(I) Complexes as Models for Monocopper Sites in Enzymes

A cavity that acts as a molecular funnel is formed from calix[6]arene 1 and [Cu^I(NCCH₃)₄]PF₆ [Eq. (a)]. An exchange of the well-protected acetonitrile ligand for other nitriles RCN is only possible with small R groups. The protection of the copper ions precludes oxidative dimerization; thus, the complexes mimic the mononuclear site of copper enzymes.     

Asymptotic properties of solutions to some nonlinear integral equations of convolution type

For a class of nonlinear integral equations of convolution type we give necessary and sufficient conditions for the boundedness of nonnegative solutions. Moreover, conditions for the solution to converge asymptotically to a determined limit are obtained.     

Reflectance anisotropy spectra of the diamond (100)-(2x1) surface: evidence of strongly bound surface state excitons

We compare the results of ab initio calculations with measured reflection anisotropy spectra and show that strongly bound surface-state excitons occur on the clean diamond (100) surface. These excitons are found to have a binding energy close to 1 eV, the strongest ever observed at a semiconductor surface. Important electron-hole interaction effects on the line shape of the optical transitions above the surface-state gap are also found.     

Effect of molecular binding to a semiconductor on metal/molecule/semiconductor junction behavior

Diodes made by (indirectly) evaporating Au on a monolayer of molecules that are adsorbed chemically onto GaAs, via either disulfide or dicarboxylate groups, show roughly linear but opposite dependence of their effective barrier height on the dipole moment of the molecules. We explain this by Au-molecule (electrical) interactions not only with the exposed end groups of the molecule but also with its binding groups. We arrive at this conclusion by characterizing the interface by in situ UPS-XPS, ex situ XPS, TOF-SIMS, and Kelvin probe measurements, by scanning microscopy of the surfaces, and by current-voltage measurements of the devices. While there is a very limited interaction of Au with the dicarboxylic binding groups, there is a much stronger interaction with the disulfide groups. We suggest that these very different interactions lead to different (growth) morphologies of the evaporated gold layer, resulting in opposite effects of the molecular dipole on the junction barrier height.