Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC₅₀ values of 1.7 ± 0.5 μM for 11 and 2.0 ± 0.7 μM for 12) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.     

Responding to threat: Hemispheric asymmetries and interhemispheric division of input.

This investigation examined how hemispheric asymmetry and interhemispheric processing contribute to attentional biases toward emotional information. Participants (n?=?88) named the color of lateralized squares presented concurrently with neutral, positive, or threatening words. A left-hemisphere advantage in color naming was reduced when distractors were emotional, suggesting right-hemisphere priming by emotional stimuli. Furthermore, the advantage of dividing the word and color across visual fields was increased for emotion words when they were frequently presented, indicating a strategic use of interhemispheric division of labor to reduce the distracting effect of emotional words. Finally, participants with high levels of anxious apprehension were most likely to make use of this interhemispheric processing strategy, supporting a processing efficiency theory of cognitive function in anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anti-Hebbian learning in topologically constrained linear networks:a tutorial

Using standard results from the adaptive signal processing literature, we review the learning behavior of various constrained linear neural networks made up of anti-Hebbian synapses, where learning is driven by the criterion of minimizing the node information energy. We point out how simple learning rules of Hebbian type can provide fast self-organization, under rather wide connectivity constraints. We verify the results of the theory in a set of simulations.     

Restoration of polymorphonuclear leukocyte function in elderly subjects by thymomodulin

Senescence is a specific physiological evolution of human beings associated with a reduction in the functionality of several apparatuses, including the immune system. Thymomodulin (TMD) contains thymus polypeptides (< 10,000 D) and it has been used in a variety of disorders associated with defective immunological functions. The aim of this study was to investigate the effect on polymorphonuclear leukocyte (PMNs) phagocytosis and oxidative burst of a 6-week treatment with 160 mg/day TMD orally in elderly subjects (85.5 +/- 9.7 years). Elderly subjects have impaired PMN phagocytosis and the following release of oxidant radicals. Treatment with TMD for 6 weeks had a restoring effect; phagocytosis and the phagocytic index were significantly improved, with increases of 132.6% and 112.5%. These findings indicate that TMD might be given to enhance the immunodefenses of immunocompromised elderly subjects. Luminol-dependent chemiluminescence was increased by 15.6%, which was not significant, indicating a different response between phagocytosis and release of oxidant radicals.     

Characterization of superconducting thin films by Mo75Re25 target for rf cavity applications

superconducting thin films by Mo₇₅Re₂₅ single-target magnetron sputtering at various temperatures on sapphire substrates were prepared. Sharp superconductive transitions andT _c values above 10 K were achieved, and the deposited films showed a good metallic behavior. According to structural analyses (EDS and X-rays), all the samples have the same stoichiometry as the target and, even at low deposition temperatures, they exhibit theA15 phase. From measured residual resistivities and superconducting critical temperatures the theoretical BCS surface resistances were estimated and compared to those o Mo₆₀Re₄₀ films, presented in a previous work. Both these alloys, in fact, being characterized by low surface resistances and high critical fields, are good candidates as coating films in r.f. cavities.     

Thyroiditic reactions during a course of thyroid cancer

The clinical, immunological, and immunoistochemical features of 10 thyroid cancers associated with intra and extra tumoral thyroiditis are described. These cases have been obtained from a review of 806 thyroidectomies. A proper distinction of the described pathology from the immunological and histological point of view, is emphasized, especially if compared with the prognosis of other thyroid cancers.     

Production of a Coacervate Film for Microcapsule Diffusion Studies

Until the last five years, study of microcapsules formed by complex coacervation has been approached almost entirely on an empirical basis. The gelatin-acacia coating formed through complex coacervation is responsible for the sustained release characteristics of the dosage form. Because dissolution of the drug from microcapsules is often limited by the structure and nature of the shell wall, of prime interest would be the construction of an acacia-gelatin film for diffusion studies. Apparent optimal conditions for production of the coacervate film were developed. The conditions were similar to those used to produce microcapsules by various researchers. These conditions produced a coacervate film which could be cut into two square centimeter sections apparently suitable for diffusion studies. Films produced by complex coacervation appeared free from structural defects when observed with a stereo-microscope.     

Utilization of Deaeration via Gas Permeation and Oxidative Stabilization of Pyrogallol

The rates of oxidative decomposition for pyrogallol were determined at 3.0° in vehicles which had been prepared by passing deionized distilled water through a gas permeator. The vehicles prepared by gas permeation possessed varying dissolved oxygen concentrations which depended upon charging pressure and the residence time of effluent. A single pass through the permeator produced vehicles possessing dissolved oxygen concentrations of 05 ppm to 0.78 ppm with respect to a normal oxygen content of 8-9 ppm. A double pass through the permeator gave only trace amounts of dissolved oxygen. i.e., 0.01-0.02 ppm and this was found to be independent of charging pressure.     

A novel technique for flat-embedding cryofixed plant specimens in LR white resin

Acrylic LR White is used preferentially for many research applications because it possesses unique advantages over other commercially available resin types. LR White has low toxicity; its low viscosity and hydrophilic properties enable it to infiltrate specimens with comparative ease, and specimens embedded in LR White take up stains for light microscopy well and tend to retain superior antigenicity relative to other resins. These qualities make LR White a good choice for immunohistochemistry, light microscopy, and transmission electron microscopy. However, LR White does not heat-polymerize in the presence of oxygen, which precludes its use with many commercially available embedding molds. Furthermore, flat-embedding specimens in LR White is often an arduous task. Therefore, in this paper, we report on the development of novel flat-embedding chambers for use with LR White. Another goal of our studies was the rapid fixation of larger specimens. Chemical fixation was inadequate because of the time required for tissue infiltration, but cryofixation quickly and effectively immobilized intracellular organelles. Mean amyloplast positions differed in vertically oriented versus control specimens after chemical fixation, whereas no significant difference was observed after cryofixation. Furthermore, cryofixation provided acceptable preservation at the light microscopy level, even though our specimens were relatively larger. This underscores the utility of cryofixation for light microscopy determination of organelle positioning within plant cells.