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.     

A numerical modelling for the extraction of decay regions from color images of monuments

An innovative application focused on the segmentation of decay zones from images of stone materials is presented. The adopted numerical approach to extract decay regions from the color images of monuments provides a tool that helps experts analyze degraded regions by contouring them. In this way even if the results of the proposed procedure depend on the evaluation of experts, the approach can be a contribution to improving the efficiency of the boundary detection process. The segmentation is a process that allows an image to be divided into disjoint zones so that partitioned zones contain homogeneous characteristics. The numerical method, used to segment color images, is based on the theory of interface evolution, which is described by the eikonal equation. We adopted the fast marching technique to solve the upwind finite difference approximation of the eikonal equation. The fast marching starts from a seed point in the region of interest and generates a front which evolves according to a specific speed function until the boundary of the region is identified. We describe the segmentation results obtained with two speed functions, attained by the image gradient computation and color information about the object of interest. Moreover, we present the extension of the working modality of the method by introducing the possibility to extract the regions not only in a local way but also in a global way on the entire image. In this case, in order to improve the segmentation efficiency the application of the fast marching technique starts with more seed points defined as seed regions. The study case concerns the impressive remains of the Roman Theatre in the city of Aosta (Italy). In the image segmentation process the color space L^∗a^∗b^∗$L^{\ast }{a}^{\ast }{b}^{\ast }$ is utilized.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.     

Induced maturation of frog mast cells by nerve growth factor during ontogenesis

The effect of nerve growth factor (NGF) on ontogenesis of frog mast cells was investigated in vivo by histochemical, morphometric, and ultrastructural analysis. Three groups of tadpoles at various stages of development were used. In the first group, the larvae received i.p. injections of 1 ng NGF/g; the second group received 10 ng NGF/g, while the control group received only the vehicle. The first recognizable mast cells arose symmetrically in the tongue at stage 26 of Witschi's standard table. At stages 26 and 29, the mast cell number in the NGF-injected tadpoles was significantly higher than the control group. From stage 29 onward, the mast cell number rapidly increased in all groups. No significant differences in mast cell number were observed between the control group and the NGF-injected groups at stages 31 and 33. Electron microscopy revealed that at metamorphic climax (stage 33), the mast cells in the NGF-treated groups were more mature than those in the control group. Therefore, nerve growth factor at early stages of tadpole development is likely to induce differentiation of mast cell precursors, while at later stages it is likely to induce maturation of immature mast cells. The close anatomical association between mast cells and perineurium, observed during nerve development, is intriguing. Already in the early stages of nerve development, the mast cells form a network around Schwann cell-axon complexes, together with the perineurial cells. At climax, the mast cells are located between the perineurial layers, suggesting that they may play a role in the tissue-nerve barrier of the perineurium. Nerve growth factor also seems to induce perineurial cell maturation.     

Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice

The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, demonstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension. The acute effects of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.     

The Effect of Electrospun Gelatin Fibers Alignment on Schwann Cell and Axon Behavior and Organization in the Perspective of Artificial Nerve Design

Electrospun fibrous substrates mimicking extracellular matrices can be prepared by electrospinning, yielding aligned fibrous matrices as internal fillers to manufacture artificial nerves. Gelatin aligned nano-fibers were prepared by electrospinning after tuning the collector rotation speed. The effect of alignment on cell adhesion and proliferation was tested in vitro using primary cultures, the Schwann cell line, RT4-D6P2T, and the sensory neuron-like cell line, 50B11. Cell adhesion and proliferation were assessed by quantifying at several time-points. Aligned nano-fibers reduced adhesion and proliferation rate compared with random fibers. Schwann cell morphology and organization were investigated by immunostaining of the cytoskeleton. Cells were elongated with their longitudinal body parallel to the aligned fibers. B5011 neuron-like cells were aligned and had parallel axon growth when cultured on the aligned gelatin fibers. The data show that the alignment of electrospun gelatin fibers can modulate Schwann cells and axon organization in vitro, suggesting that this substrate shows promise as an internal filler for the design of artificial nerves for peripheral nerve reconstruction.