Improved in vitro anti-tumoral activity, intracellular uptake and apoptotic induction of gemcitabine-loaded pegylated unilamellar liposomes

Anaplastic thyroid carcinoma is one of the most aggressive and lethal solid carcinomas affecting humans. A major limit of the chemotherapeutic agents is represented by their low therapeutic index. In this work, we investigated the possibility of improving the anti-tumoral activity of gemcitabine by using pegylated unilamellar liposomes. Liposomes were made up of 1,2-dipalmitoyl-sn-glycero-3-phospocholine monohydrate/cholesterol/N-(carbonyl-methoxypolyethylene glycol-2000)-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (6:3:1 molar ratio) and they were prepared with a pH gradient to improve the gemcitabine loading capacity. The anti-tumoral efficacy of the liposomal formulation was tested in vitro on human anaplastic thyroid carcinoma cells (ARO) in culture, comparing the effects with those of the free drug. Gemcitabine-loaded unilamellar liposomes had a mean size approximately 200 nm with a zeta potential approximately -2 mV. The liposomal carrier noticeably improved the anti-tumoral activity of gemcitabine against ARO cells in terms of both dose-dependent cytotoxic effect and of drug exposition effect. Namely, gemcitabine-loaded liposomes showed a cytotoxic effect (58.2% increase of cell mortality at 1 microM with respect to free drug) after 12 h incubation, while the free drug showed a significant activity only after 72 h incubation. Moreover, a significant effect on the cell mortality appeared at 0.1 microM and 100% mortality was detected at a concentration of 1 microM of gemcitabine-loaded liposomes, while the free drug elicited the same effect at a concentration of 100 microM. The improved anti-tumoral activity of gemcitabine determined by the liposomal carrier was due to a greater intracellular uptake. The intracellular gemcitabine levels as a function of time showed a sinusoidal profile with peaks after 2 h, 6 h and 11 h, related to the cellular cycle of ARO. PARP cleavage and DNA fragmentation analysis provided clear evidence of the apoptosis induction in ARO cells by treatment with liposomally entrapped gemcitabine after 72 h incubation. Thus, gemcitabine-loaded liposomes may have a potential therapeutic relevance for the treatment of anaplastic thyroid carcinoma.     

Design and behavior study of a grammar-guided genetic programming algorithm for mining association rules

This paper presents a proposal for the extraction of association rules called G3PARM (Grammar-Guided Genetic Programming for Association Rule Mining) that makes the knowledge extracted more expressive and flexible. This algorithm allows a context-free grammar to be adapted and applied to each specific problem or domain and eliminates the problems raised by discretization. This proposal keeps the best individuals (those that exceed a certain threshold of support and confidence) obtained with the passing of generations in an auxiliary population of fixed size n. G3PARM obtains solutions within specified time limits and does not require the large amounts of memory that the exhaustive search algorithms in the field of association rules do. Our approach is compared to exhaustive search (Apriori and FP-Growth) and genetic (QuantMiner and ARMGA) algorithms for mining association rules and performs an analysis of the mined rules. Finally, a series of experiments serve to contrast the scalability of our algorithm. The proposal obtains a small set of rules with high support and confidence, over 90 and 99% respectively. Moreover, the resulting set of rules closely satisfies all the dataset instances. These results illustrate that our proposal is highly promising for the discovery of association rules in different types of datasets.     

The validity of a game-based assessment of persistence

In this study, 154 students individually played a challenging physics video game for roughly 4 h. Based on time data for both solved and unsolved problems derived from log files, we created a game-based assessment of persistence that was validated against an existing measure of persistence. We found that the game-based assessment of persistence predicted learning of qualitative physics after controlling for gender, video game experience, pretest knowledge and enjoyment of the game. These findings support the implementation of a real-time formative assessment of persistence to be used to dynamically change gameplay.     

Determination of ultratrace levels of selenium in fruit and vegetable samples grown and consumed in Portugal

The selenium content in fruit and vegetable samples from two regions in Portugal were analysed using hydride generation atomic fluorescence spectrometry (HG-AFS) and radiochemical nuclear activation analysis (RNAA) – two analytical methods with very low limits of detection. The lower detection limits of HG-AFS, 3 μg kg⁻¹ and 8 μg kg⁻¹ (according to conditions used for digestion), and for RNAA, 10 μg kg⁻¹, meant that it was possible to determine selenium in samples previously analysed using the replicate sample instrumental nuclear activation analysis (RSINAA) with a higher detection limit associated.     

Lyoprotected nanosphere formulations for paclitaxel controlled delivery

The preparation and technological characterization of nanosphere formulations (NS) containing the anticancer drug paclitaxel (PTX) are reported. Poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by a solvent displacement method. They showed a mean particle size in the range 150-300 nm, with a high homogeneity (polydispersity index < 0.3). For long term stability, NS require additional procedures, such as freeze-drying. In this study, the effect on NS particle size and surface charge of different lyoprotectants (mono- and disaccharides, polyalcohols, and hydroxypropyl-beta-cyclodextrin) at various concentrations was tested by means of light scattering size analysis. The formulations freeze-dried with the addition of 10% glucose (w/v) showed interesting characteristics after freeze-drying. They were chosen for specific studies on drug encapsulation efficiency, in vitro drug release and biological activity on the human anaplastic thyroid carcinoma cell line 8305C. The PLGA NS, in particular, showed a cell growth inhibitory activity comparable to the free drug.     

Cactus stem (Opuntia ficus‐indica Mill): anatomy,physiology and chemical composition with emphasis on its biofunctional properties

Cactus stem (Opuntia ficus‐indica Mill) is native to Mesoamerica and marketed in different forms such as fresh, frozen or pre‐cooked. Worldwide, this vegetable is recognized for its pharmaceutical actions, including its antioxidant, diuretic, anticarcinogenic, anti‐inflammatory, anti‐diabetic, and anti‐hypercholesterolemic properties, as well as their antiviral and antispermatogenic effects. However, not all of these properties have been associated with its chemical composition; therefore, this review aims to present and integrate information available on the physiology and anatomy of cactus stem and its chemical composition, focusing on some of the many factors that determine its biofunctionality. © 2017 Society of Chemical Industry     

Scheduling flexible manufacturing cells using Tabu Search

Scheduling is an important aspect in the overall control of a flexible manufacturing system. The research presented focuses on production scheduling of jobs within a flexible manufacturing cell (FMC)–one type of flexible manufacturing system. Due to the complexity of the FMC scheduling problem, a 0–1 mixed-integer linear programming (MILP) model is formulated for M machines and N jobs with alternative routings. Although small instances of the problem can be solved optimally with MILP models, a two-stage Tabu Search (TS² ) algorithm that minimises the manufacturing makespan (MS) is proposed to solve medium-to-large-scale problems more efficiently. During Stage I (construction phase), two heuristics are utilised to generate an initial feasible sequence and an initial MS solution. In Stage II (improvement phase), the acquired initial solutions from Stage I are combined with a Tabu Search meta-heuristic procedure that provides improved MS solutions. The TS² algorithm provides tremendous savings in computational time for medium/large-sized multi-machine FMC problems.