Design and synthesis of a biotinylated probe of COX-2 inhibitor nimesulide analog JCC76

JCC76 is a derivative of cyclooxygenase-2(COX-2) selective inhibitor nimesulide and exhibits potent anti-breast cancer activity. It selectively induces apoptosis of Her2 positive breast cancer cells. However, the specific molecular targets of JCC76 still remain unclear, which significantly withdraw the further drug development of JCC76. To identify the molecular targets of JCC76, a six carbon linker and biotin conjugated JCC76 probe was designed and synthesized. The anti-proliferation activity of the probe and its analogs was evaluated.     

Fabrication of Monodispersed Silver Nanoparticles and their Collective Sharp Plasmonic Response

Monodispersed silver (Ag) nanoparticles (NPs) were obtained by applying an electric field on unipolar-charged Ag NPs fabricated using a heterogeneous condensation technique in gas media. Well defined and charged Ag NPs were separated based on their sizes and were collected on quartz substrates. Thin films consisting of monodispersed Ag NPs with size ranging from 35 to 120 nm were prepared by varying an applied electric field during the fabrication process. Scanning electron microscope results showed that the samples have uniform size distribution. Coherent oscillations of conduction band electrons in gas medium induced by electromagnetic field and coupling of all similar plasmon resonances due to uniform Ag NPs size produced unique and interesting optical properties. Narrow extinction widths (～41 to ～69 nm) were observed compared to the width of polydispersed Ag sample. The ability to prepare samples in gas media and tune the plasmon resonance by merely varying an electric field during fabrication makes the method simple, fast, and highly economical.     

Genetic differentiation of the Euglossini (Hymenoptera, Apidae) populations on a mainland coastal plain and an island in southeastern Brazil

Euglossini bees are among the main pollinators of plant species in tropical and subtropical forests in Central and South America. These bees are known as long-distance pollinators due to their exceptional flight performance. Here we assessed through microsatellite loci the gene variation and genetic differentiation between populations of four abundant Euglossini species populations sampled in two areas, Picinguaba (mainland) and Anchieta Island, Ubatuba, São Paulo State, southeastern Brazil. There was no significant genetic differentiation between the island and mainland samples of Euglossa cordata (Fst = 0.008, P = 0.60), Eulaema cingulata (Fst = 0.029, P = 0.29) and Eulaema nigrita (Fst = 0.062, P = 0.38), but a significant gene differentiation between mainland and island samples of Euglossa stellfeldi (Fst = 0.028, P = 0.016) was detected. As expected, our results showed that the water body that separates the island from the mainland does not constitute a geographic barrier for these Euglossini bees. The absence of populational structuring of three out the four species studied corroborates previous reports on those bees, characterized by large populations, with high gene diversity and gene flow and very low levels of diploid males. But the Eg. stellfeldi results clearly point that dispersal ability is not similar to all euglossine bees, what requires the development of different conservationist strategies to the Euglossini species.     

Development,validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing

It has been demonstrated that two-dimensional (2D) monolayer cancer cell proliferation assay for anti-cancer drug screening is a very artificial model and cannot represent the characteristics of three-dimensional (3D) solid tumors. The multi-cellular in vitro 3D tumor spheroid model is of intermediate complexity, and can provide a bridge to the gap between the complex in vivo tumors and simple in vitro monolayer cell cultures. In this study, a simple and cost-effective cancer 3D spheroid assay suitable for small molecule anti-cancer compound screening was developed, standardized and validated on H292 non-small lung cancer cell line. A pilot screening with this assay was performed utilizing a compound library consisting of 41 anti-cancer agents. The traditional 2D monolayer cell proliferation assay was also performed with the same cell line and compounds. A correlational study based on the IC₅₀ values from the 2D and 3D assays was conducted. There is low correlation with the two sets of biological data, suggesting the two screening methods provide different information regarding the potency of the tested drug candidates.     

Sinus aspergilloma in rheumatoid arthritis before or during tumor necrosis factor-alpha antagonist therapy

Introduction  

In 2008, the Food and Drugs Administration required manufacturers of TNFα antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid arthritis (RA). Sinus aspergilloma occurs occasionally in RA patients and can progress to invasive Aspergillus disease. The purpose of this study was to describe symptomatic sinus aspergilloma in RA patients treated with TNFα antagonists.     

Antibiofilm action of a toluidine blue O-silver nanoparticle conjugate on Streptococcus mutans: a mechanism of type I photodynamic therapy

The objective of this study was to evaluate the anti-biofilm efficacy of photodynamic therapy by conjugating a photosensitizer (TBO) with silver nanoparticles (AgNP). Streptococcus mutans was exposed to laser light (630 nm) for 70 s (9.1 J cm^?2) in the presence of a toluidine blue O–silver nanoparticle conjugate (TBO–AgNP). The results showed a reduction in the viability of bacterial cells by 4 log₁₀. The crystal violet assay, confocal laser scanning microscopy and scanning electron microscopy revealed that the TBO–AgNP conjugates inhibited biofilm formation, increased the uptake of propidium iodide and leakage of the cellular constituents, respectively. Fluorescence spectroscopic studies confirmed the generation of OH^? as a major reactive oxygen species, indicating type I phototoxicity. Both the conjugates down-regulated the expression of biofilm related genes compared to TBO alone. Hence TBO–AgNP conjugates were found to be more phototoxic against S. mutans biofilm than TBO alone.