Sounds Stimulation on In Vitro HL1 Cells: A Pilot Study and a Theoretical Physical Model

Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves’ geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.     

Evaluation of direct light processing for the fabrication of bioactive ceramic scaffolds: Effect of pore/strut size on manufacturability and mechanical performance

Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds.     

Susceptor-assisted fast microwave sintering of TiN reinforced SiAlON composites in a single mode cavity

In the present study, 17 wt % TiN reinforced α-β SiAlON composites were sintered at low temperature by susceptor-assisted microwave heating. The effect of TiN addition on dielectrical properties of starting powders, as well as the influence of sintering temperature on phase evolution, microstructure development and mechanical properties of α/β-SiAlON-TiN composites were investigated. The obtained results showed that TiN addition increased the microwave absorbing properties which is reflected in the peak sintering temperature. Thus, the α:β ratio decreased and mechanical properties were improved, especially the fracture toughness of the composites. Furthermore, an estimate of energy consumption during microwave assisted sintering at the laboratory scale is presented. As a result, the highest values for relative density (97.1%), Vickers hardness (13.35 ± 0.47 GPa), and fracture toughness (7.52 ± 0.54 MPa m^1/2) were obtained by microwave sintering for 30 min at 1300 °C.     

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.     

Fabrication of ceramic particles from preceramic polymers using stop flow lithography

Stop flow lithography (SFL) combines aspects of microfluidic and photolithography to continuously fabricate particles with uniform planar shapes as dictated by a mask. In this work we aim to expand the palette of materials suitable for SFL processing by investigating the use of UV-crosslinkable preceramic polymers to make ceramic particles. A commercially available methacrylated-polysiloxane was used as the preceramic polymer and was mixed with 2.5 wt% Irgacure 651 photoinitiator. A simple SFL system was assembled to continuously fabricate UV-crosslinked preceramic polymer particles in the shape of hexagons, triangles, and gears with diameters ranging from 100 to 200 μm and thicknesses of 74 μm +/- 4 μm. Particles were harvested from the excess preceramic solution, cleaned and then pyrolyzed at 1000 °C to transform them into silicon oxycarbide ceramic particles. Particle shape was maintained during pyrolysis despite a ～80 % linear shrinkage due to the removal of acryl and methyl side groups, as confirmed via FTIR. After pyrolysis the outer diameters of the SiOC particles ranged from 20 to 40 μm with thicknesses of 10 μm–12 μm. Pyrolyzed particles were successfully recovered and dispersed in water. This work demonstrates a robust path for the fabrication of ceramic particles with specific shapes from preceramic polymers via SFL.     

Strategies to Modulate Specialized Metabolism in Mediterranean Crops: From Molecular Aspects to Field

Plant specialized metabolites (SMs) play an important role in the interaction with the environment and are part of the plant defense response. These natural products are volatile, semi-volatile and non-volatile compounds produced from common building blocks deriving from primary metabolic pathways and rapidly evolved to allow a better adaptation of plants to environmental cues. Specialized metabolites include terpenes, flavonoids, alkaloids, glucosinolates, tannins, resins, etc. that can be used as phytochemicals, food additives, flavoring agents and pharmaceutical compounds. This review will be focused on Mediterranean crop plants as a source of SMs, with a special attention on the strategies that can be used to modulate their production, including abiotic stresses, interaction with beneficial soil microorganisms and novel genetic approaches.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Trans-differentiation of human adipose-derived mesenchymal stem cells into cardiomyocyte-like cells on decellularized bovine myocardial extracellular matrix-based films

In this study, we aimed at fabricating decellularized bovine myocardial extracellular matrix-based films (dMEbF) for cardiac tissue engineering (CTE). The decellularization process was carried out utilizing four consecutive stages including hypotonic treatment, detergent treatment, enzymatic digestion and decontamination, respectively. In order to fabricate the dMEbF, dBM were digested with pepsin and gelation process was conducted. dMEbF were then crosslinked with N-hydroxysuccinimide/1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (NHS/EDC) to increase their durability. Nuclear contents of native BM and decellularized BM (dBM) tissues were determined with DNA content analysis and agarose-gel electrophoresis. Cell viability on dMEbF for 3rd, 7th, and 14th days was assessed by MTT assay. Cell attachment on dMEbF was also studied by scanning electron microscopy. Trans-differentiation capacity of human adipose-derived mesenchymal stem cells (hAMSCs) into cardiomyocyte-like cells on dMEbF were also evaluated by histochemical and immunohistochemical analyses. DNA contents for native and dBM were, respectively, found as 886.11?±?164.85 and 47.66?±?0.09?ng/mg dry weight, indicating a successful decellularization process. The results of glycosaminoglycan and hydroxyproline assay, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), performed in order to characterize the extracellular matrix (ECM) composition of native and dBM tissue, showed that the BM matrix was not damaged during the proposed method. Lastly, regarding the histological study, dMEbF not only mimics native ECM, but also induces the stem cells into cardiomyocyte-like cells phenotype which brings it the potential of use in CTE.