Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.     

Relationship between word difficulty and access of single-word meaning by skilled and less skilled readers.

Previous research, by R. M. Golinkoff and R. R. Rosinski (1976), used a picture-word interference task to show that skilled and less skilled comprehenders in the 3rd and 5th grades could retrieve the meaning of primer-level words equally well. With a similar task and comparable groups of children ( N = 64), the present study assessed the relationship between word difficulty and semantic access by using both the easy words and a new set of more difficult words. Retrieval of the meaning of these difficult words was least apparent for the less skilled 3rd graders, the group that had the most difficulty decoding these words. Results indicate that decoding ease and extraction of word meanings are related and also suggest that decoding ability must be considered a factor in reading comprehension. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery of platinum, tin and indium from spent catalysts in chloride medium using strong basic anion exchange resins

This work describes a route for platinum recovery from spent commercial Pt and PtSnIn/Al₂O₃ catalysts using strong basic mesoporous and macroporous anion exchange resins (Cl⁻ form). The catalysts were leached with aqua regia (75 °C, 20-25 min). Platinum adsorption was influenced by the presence of other metals which form chlorocomplexes (tin, indium) and also base metals (aluminum). However, it was possible to overcome this fact by a sequential desorption procedure. Aluminum was selectively removed from the resins by elution with 3 mol L⁻¹ HCl. Platinum was desorbed passing 1 mol L⁻¹ Na₂S₂O₃ (pH 9). Tin was removed by elution with 0.1 mol L⁻¹ ascorbic acid. Indium was removed using 0.1 mol L⁻¹ EDTA as eluent. Desorption efficiency exceeded 99% for all metals. Metals were recovered in high yields (>98 wt%).     

Validation of the performance of a GMO multiplex screening assay based on microarray detection

A new screening method for the detection and identification of GMO, based on the use of multiplex PCR followed by microarray, has been developed and is presented. The technology is based on the identification of quite ubiquitous GMO genetic target elements first amplified by PCR, followed by direct hybridisation of the amplicons on a predefined microarray (DualChip^® GMO, Eppendorf, Germany). The validation was performed within the framework of a European project (Co-Extra, contract no 007158) and in collaboration with 12 laboratories specialised in GMO detection. The present study reports the strategy and the results of an ISO complying validation of the method carried out through an inter-laboratory study. Sets of blind samples were provided consisting of DNA reference materials covering all the elements detectable by specific probes present on the array. The GMO concentrations varied from 1% down to 0.045%. In addition, a mixture of two GMO events (0.1% RRS diluted in 100% TOPAS19/2) was incorporated in the study to test the robustness of the assay in extreme conditions. Data were processed according to ISO 5725 standard. The method was evaluated with predefined performance criteria with respect to the EC CRL method acceptance criteria. The overall method performance met the acceptance criteria; in particular, the results showed that the method is suitable for the detection of the different target elements at 0.1% concentration of GMO with a 95% accuracy rate. This collaborative trial showed that the method can be considered as fit for the purpose of screening with respect to its intra- and inter-laboratory accuracy. The results demonstrated the validity of combining multiplex PCR with array detection as provided by the DualChip^® GMO (Eppendorf, Germany) for the screening of GMO. The results showed that the technology is robust, practical and suitable as a screening tool.     

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

A comparison of fitting algorithms for diffusion-weighted MRI data analysis using an intravoxel incoherent motion model

Object

The objective of this study is to propose a modified VARiable PROjection (VARPRO) algorithm specifically tailored for fitting the intravoxel incoherent motion (IVIM) model to diffusion-weighted magnetic resonance imaging (DW-MRI) data from locally advanced rectal cancer (LARC).

Materials and methods

The proposed algorithm is compared with classical non-linear least squares (NLLS) analysis using the Levenberg-Marquardt (LM) algorithm and with two recently proposed algorithms for ‘segmented’ analysis. These latter two comprise two consecutive steps: first, a subset of parameters is estimated using a portion of data; second, the remaining parameters are estimated using the whole data and the previous estimates. The comparison between the algorithms was based on the \(R^2\) goodness-of-fit measure: performance analysis was carried out on real data obtained by DW-MRI on 40 LARC patients.

Results

The performance of the proposed algorithm was higher than that of LM in 64 % of cases; ‘segmented’ methods were poorer than our algorithm in 100 % of cases.

Conclusion

The proposed modified VARPRO algorithm can lead to better fit of the IVIM model to LARC DW-MRI data compared to other techniques.

     

Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents

Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds.     

Pd/Ce0.6Zr0.4O2/Al2O3 as advanced materials for three-way catalysts: Part 1. Catalyst characterisation, thermal stability and catalytic activity in the reduction of NO by CO

Pd-loaded Ce_0.6Zr_0.4O₂ solid solutions supported on Al₂O₃ are investigated as catalysts for the reduction of NO by CO. The attention is focused on the role of the Ce_0.6Zr_0.4O₂ and of the Pd dispersion on the catalytic activity. The system shows a very high activity below 500 K, which is almost independent on the Pd dispersion. The high activity is attributed to a promoting effect of the Ce_0.6Zr_0.4O₂ on the NO conversion. Investigation of the influence of high temperature treatments disclosed a thermal stabilisation of both Ce_0.6Zr_0.4O₂ and Al₂O₃ in the Ce_0.6Zr_0.4O₂/Al₂O₃ system.     

Diet effects in the asthma treatment: A systematic review

Introduction: Obesity in asthmatic patients has important relationships with asthma control, pulmonary function, and quality of life. The objective of this study was to conduct a systematic review of the literature on the effect of diet on asthma management in adults. Methods: We searched PubMed, Embase, and Scopus (January 1948–October 2014) for randomized clinical trials that evaluated the effects of diet in adults with asthma. Results: Of 12,215 studies identified, 21 were included. A reduction in weight of at least 7.5% from baseline as a result of caloric restriction can be beneficial for improving disease control, quality of life, and pulmonary function in obese patients with asthma. A dietary pattern rich in foods with potential antioxidant effect had an impact in improving asthma control, but with little clinical significance. Studies involving antioxidant supplementation showed improvements in asthma control with magnesium supplementation and less decline in lung function with vitamin C supplementation. Studies of fatty acid supplementation demonstrated effects on weight loss and improvement of asthma control and lung function. Studies of supplementation with propolis and caffeine reported significant increases in FEV1. Conversely, studies of high dietary salt intake reported greater declines in lung function. Conclusions: The evidence shows that, for obese adults with asthma, the best dietary intervention seems to be caloric restriction, regardless of specific dietary components.     

Silver electrodeposition from air and water-stable ionic liquid: An environmentally friendly alternative to cyanide baths

The influence of temperature on the kinetics and the morphology of silver deposits obtained from an air and water-stable ionic liquid (the 1-butyl-3-methyl imidazolium tetrafluoroborate) was studied by means of cyclic voltammetry and chronoamperometry. The nucleation and growth mechanisms have been investigated and the effect of temperature evaluated up to 200 °C. Dense, pure and very thin (about 0.3 μm) silver coatings, with decorative properties, have been obtained on commercial copper electrodes at different temperatures. The characterization of the deposits morphology has been performed by visual investigation and SEM microscopy. Data about thickness were acquired by Calotest® measurements. The deposits result constituted by pure silver as determined by combination of EDX microanalysis and Auger Electron Spectroscopy (AES). The deposition method promises to be a new, environmentally friendly, method for silver electrodeposition which is the reason for the absence of cyanide and volatile toxic solvents in the electroplating bath.