The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Thermo-physical properties of as deposited and aged thermal barrier coatings (TBC) for gas turbines: State-of-the art and advanced TBCs

In the perspective of fuelling the future generations of gas turbines by hydrogen rich syngas, the evaluation of the effect of a higher water vapour content into the flue gases on the TBC used, or potentially usable, is a need. For this purpose YPSZ APS TBC with two different microstructures have been exposed for 500?h at different temperatures in the range 1000?°C–1250?°C either in air and air +20% vol. H₂O. The comparison between the different testing conditions has been performed in terms of sintering kinetics and phase stability, as evaluated by thermal diffusivity measurements and Synchrotron X-Rays diffraction, respectively. Furthermore the characterisation of thermal properties of two innovative TBCs (GZO-YPSZ and YAG) potentially able to withstand the CMAS attack and erosive environments, respectively, has been carried out.No clear evidence of a different behaviour of TBC has been observed, at least in the considered aging time and temperature range.     

Endoplasmic reticulum Ca(2+)-ATPase in microsomal vesicles isolated from bovine retinae

Active Ca2+ transport was measured in microsomal vesicles prepared from bovine retinae and was compared with that in disk membranes of the photoreceptor cells of the same retina. The 45Ca uptake was dependent on the presence of Mg(2+)-ATP and was inhibited by vanadate or when GTP substituted for ATP. The dependence of calcium uptake on the external free Ca2+ concentration gave a KM = 13 microM or a KM = 0.1 microM for disks and microsomal vesicles, respectively. A phosphorylated intermediate (E-P) of Ca(2+)-ATPase of about 100 kDa was isolated in microsomal vesicles. The E-P formation was strongly inhibited by thapsigargin and partially by 2,5-di-(-butyl)benzohydroquinone. Digestion of disks or microsomes with calpain had no effect on the phosphorylated intermediate, while digestion with trypsin produced two fragments of approximately 55 kDa and 35 kDa. These results suggest that bovine retinal microsomes contain a calcium pump belonging to the SERCA family.     

The Strategic Control of Multiple Routes in Imitation of Actions.

The aim of this study was to bring to the surface the strategic use of imitative processes in the context of a 2-route model: (a) direct imitation, used in reproducing new, meaningless actions, and (b) imitation based on stored semantic knowledge of familiar meaningful actions. Three experiments were carried out with healthy participants who reproduced meaningful and meaningless actions within an established time limit. The study investigated 3 factors that could potentially affect the selection of processes used for imitation: (a) the composition of the experimental list (blocked or mixed presentation), (b) the presence-absence of instructions (Experiments 1 and 2), and (c) the relative proportions of the stimuli (Experiment 3). Overall, the results suggest that each of these factors influences the selection of imitative strategies in healthy individuals with temporarily reduced capacities, as happens in the case of brain-damaged patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A study on the stability of superconducting YBa2Cu3O7−x phase

The thermal stability of the superconducting phase of nominal composition YBa₂Cu₃O_7–x -sintered pellets has been studied with respect to different temperatures (ranging from 300 to 950° C), time (ranging from 1 to 72 h), oxygen partial pressure (from 4 Pa to 1 atm) and carbon dioxide partial pressure (from 10^–4 Pa to 1 atm). Annealed samples were characterized by X-ray diffraction analysis, optical microscopy, and resistive measurements of the superconductive transition temperature. A stability field of the orthorhombic and tetragonal phases was obtained, showing a region of coexistance. The decomposition of the 1 2 3 phase is found to be strongly influenced by the presence of a small amount of CO₂ (1 p.p.m.) in the sintering atmosphere. A sintering process is proposed to avoid the formation of by-products.     

Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

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.     

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

Stabilization of strict‐feedback nonlinear systems with input delay using closed‐loop predictors

In this paper, we consider the control problem of strict‐feedback nonlinear systems with time‐varying input and output delays. The approach is based on the usual observer/predictor/feedback approach, but the novelty is the use of the closed‐loop dynamics in the predictor. This approach allows to develop two designs, an instantaneous predictor and a delay differential equation‐based predictor, that both attain the same performance in terms of system trajectories and input signal as in the case with no delays. The design based on delay differential equations allows to build a cascade of predictors to deal with arbitrarily large delay bounds. The resulting controller is much simpler to implement than classical infinite‐dimensional predictors, and it is robust with respect to actuation and measurement disturbances. We illustrate the approach with an application to the control of a chaotic system with input delay. Copyright © 2016 John Wiley & Sons, Ltd.