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.     

Exploration of GH94 Sequence Space for Enzyme Discovery Reveals a Novel Glucosylgalactose Phosphorylase Specificity

The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis.     

Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers,Signaling Pathways and miRNAome

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.     

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.     

3D CaP porous scaffolds with grooved surface topography obtained by the sol-gel method

The influence of surface topography on cellular behaviour and its importance for the development of three-dimensional scaffolds for bone tissue engineering are a topic of growing interest. To date, the introduction of topographical patterns into the surface of 3D porous ceramic scaffolds has proven difficult, due partly to the brittle nature of ceramic materials as well as the currently available fabrication technologies. In this study, a grooved pattern was introduced into the surface of 3D multilayer porous ceramic scaffolds by the chemical etching technique. The patterned scaffolds were characterised by X-Ray Diffraction (XRD), Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy (SEM-EDX) and Digital Holographic Microscopy (DHM). Their bioactivity was also evaluated in vitro by immersion in simulated body fluid (SBF) for 12 h, 1, 7, 14 and 21 days. Scaffolds were constituted mainly with a mixture of the calcium pyrophosphate (Ca₂O₇P₂) and β-tricalcium phosphate (Ca?(PO?)?) phases. The pyrophosphate on the external layer was dissolved as a result of the etching process, leaving grooves on the surface. Ridges and grooves were nano-/micrometric, with dimensions of around 900 nm–1.5 μm in width and 200 nm–300 nm in depth. Moreover, the mechanical properties and bioactive capacity of the patterned scaffolds were not affected by chemical etching, making them suitable to be used in bone tissue engineering.     

Two-Dimensional Silicene–Stanene Heterostructures by Epitaxy

The synthesis of new Xenes and their potential applications prototypes have achieved significant milestones so far. However, to date the realization of Xene heterostructures in analogy with the well known van der Waals heterostructures remains an unresolved issue. Here, a Xene heterostructure concept based on the epitaxial combination of silicene and stanene on Ag(111) is introduced, and how one Xene layer enables another Xene layer of a different nature to grow on top is demonstrated. Single-phase (4 × 4) silicene is synthesized using stanene as a template, and stanene is grown on top of silicene on the other way around. In both heterostructures, in situ and ex situ probes confirm layer-by-layer growth without intercalations and intermixing. Modeling via density functional theory shows that the atomic layers in the heterostructures are strongly interacting, and hexagonal symmetry conservation in each individual layer is sequence selective. The results provide a substantial step toward currently missing Xene heterostructures and may inspire new paths for atomic-scale materials engineering.     

Algorithm selection and instance space analysis for curriculum-based course timetabling

Journal of Scheduling - We propose an algorithm selection approach and an instance space analysis for the well-known curriculum-based course timetabling problem (CB-CTT), which is an important...     

QoS metrics-in-the-loop for endowing runtime self-adaptation to robotic software architectures

Multimedia Tools and Applications - The design of robots capable of operating autonomously in changing and unstructured environments, requires using complex software architectures in which,...     

Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.