In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.     

Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O₂⁻), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O₂⁻ production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer’s disease.     

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.     

From Stem Cells to Bone-Forming Cells

Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. In this review, we briefly define the cellular identity and function of osteoblasts and discuss the main populations of osteoprogenitor cells identified to date. We also provide examples of long-known and recently recognized regulatory pathways and mechanisms involved in the specification of the osteogenic lineage, as assessed by studies on mice models and human genetic skeletal diseases.     

Laser surface texturing of ceramics and ceramic composite materials – A review

The surface texturing of ceramics is generally performed through acid-based etching and machining; however, laser texturing may be considered as a more precise, reproducible and eco-friendly process. Furthermore, laser ablation may be used to produce complex patterns on ceramic surfaces, thus offering new surface engineering opportunities. The studies so far conducted on this topic have mainly been application-driven, and since a wide variety of lasers have been used for surface texturing, it is difficult to have a comprehensive understanding of this technique applied to ceramics and ceramic composite materials. Laser texturing requires a great deal of knowledge of the material and the laser source parameters to optimise the process in order to obtain the expected results. It is therefore important to expand the research on the laser texturing of ceramics and CMCs in order to build a relevant amount of literature that can be used to identify the most appropriate parameters for each application. This review provides an overview of most of the technological aspects considered relevant for the laser surface texturing of ceramics and CMCs, and includes the fundamentals of laser-material interactions and a summary of the used equipment and parameters. Furthermore, most of the techniques related to the modifications of surface material induced by a laser are critically reviewed, and the new horizons that are opening up, in the context of the modification of surfaces to improve the performances of materials for several applications, are discussed.     

A Decision Support System Based on AHP for Ranking Strategies to Manage Emergencies on Drinking Water Supply Systems

Water Resources Management - The provision of critical services, such as drinking water, is crucial both in ordinary and in emergency conditions due to either natural (e.g. earthquakes, droughts,...     

Temperature effects on the enhanced or deteriorated buoyancy-driven heat transfer in differentially heated enclosures filled with nanofluids

ABSTRACT

A two-phase model based on the double-diffusive approach is used to perform a numerical study of natural convection in differentially heated vertical cavities filled with water-based nanofluids, assuming that Brownian diffusion and thermophoresis are the only slip mechanisms by which the solid phase can develop a significant relative velocity with respect to the liquid phase. The system of the governing equations of continuity, momentum, and energy for the nanofluid, and continuity for the nanoparticles, is solved through a computational code, which incorporates three empirical correlations for the evaluation of the effective thermal conductivity, the effective dynamic viscosity, and the thermophoretic diffusion coefficient, all based on the literature experimental data. The pressure–velocity coupling is handled using the SIMPLE-C algorithm. Numerical simulations are executed for three different nanofluids, using the diameter and the average volume fraction of the suspended nanoparticles, as well as the cavity width, the average temperature of the nanofluid, and the temperature difference imposed across the cavity, as independent variables. It is found that the heat transfer performance of the nanofluid relative to that of the base fluid increases notably with increasing the average temperature, showing a peak at an optimal particle loading. Conversely, the other controlling parameters have moderate effects.