Potential Anti-Metastatic Role of the Novel miR-CT3 in Tumor Angiogenesis and Osteosarcoma Invasion

Osteosarcoma (OS) is the most common primary bone tumor mainly occurring in young adults and derived from primitive bone-forming mesenchyme. OS develops in an intricate tumor microenvironment (TME) where cellular function regulated by microRNAs (miRNAs) may affect communication between OS cells and the surrounding TME. Therefore, miRNAs are considered potential therapeutic targets in cancer and one of the goals of research is to accurately define a specific signature of a miRNAs, which could reflect the phenotype of a particular tumor, such as OS. Through NGS approach, we previously found a specific molecular profile of miRNAs in OS and discovered 8 novel miRNAs. Among these, we deepen our knowledge on the fifth candidate renamed now miR-CT3. MiR-CT3 expression was low in OS cells when compared with human primary osteoblasts and healthy bone. Through TargetScan, VEGF-A was predicted as a potential biological target of miR-CT3 and luciferase assay confirmed it. We showed that enforced expression of miR-CT3 in two OS cell lines, SAOS-2 and MG-63, reduced expression of VEGF-A mRNA and protein, inhibiting tumor angiogenesis. Enforced expression of miR-CT3 also reduced OS cell migration and invasion as confirmed by soft agar colony formation assay. Interestingly, we found that miR-CT3 behaves inducing the activation of p38 MAP kinase pathway and modulating the epithelial-mesenchymal transition (EMT) proteins, in particular reducing Vimentin expression. Overall, our study highlights the novel role of miR-CT3 in regulating tumor angiogenesis and progression in OS cells, linking also to the modulation of EMT proteins.     

Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells

Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment.     

Design,Synthesis, Biological Activity,and Structural Analysis of Lactam‐Constrained PTPRJ Agonist Peptides

PTPRJ is a receptor‐like protein tyrosine phosphatase mainly known for its antiproliferative and tumor‐suppressive functions. PTPRJ dephosphorylates several growth factors and their receptors, negatively regulating cell proliferation and migration. We recently identified a disulfide‐bridged nonapeptide, named PTPRJ‐19 (H‐[Cys‐His‐His‐Asn‐Leu‐Thr‐His‐Ala‐Cys]‐OH), which activates PTPRJ, thereby causing cell growth inhibition and apoptosis of both cancer and endothelial cells. With the aim of replacing the disulfide bridge by a chemically more stable moiety, we have synthesized and tested a series of lactam analogues of PTPRJ‐19 . This replacement led to analogues with higher activity and greater stability than the parent peptide.     

Light emitting devices based on Si nanoclusters： the integration with a photonic-crystal and electroluminescence properties

We present the properties and potentialities of light emitting devices based on amorphous Si nanoclusters. Amorphousnanostructures may constitute an interesting alternative to Si nanocrystals for the monolithic integration of optical andelectrical functions in Si technology. In fact, they exhibit an intense room temperature electroluminescence (EL). The ELproperties of these devices have been studied as a function of current and of temperature. Moreover, to improve theextraction efficiency of the light, we have integrated the emitting system with a 2D photonic crystal structure opportunelyfabricated by using conventional optical lithography to reduce the total internal reflection of the emitted light. The extractionefficiency in such devices increases by a factor of 4 at a resonance wavelength.     

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.     

Benchmark exercise on risk assessment methods applied to a virtual hydrogen refuelling station

A benchmarking exercise on quantitative risk assessment (QRA) methodologies for hydrogen safety has been conducted within the project HyQRA, under the framework of the European Network of Excellence (NoE), HySafe. The aim of the exercise was twofold: (i) to identify the differences and similarities in approaches in a QRA and their results for a hydrogen installation and (ii) to identify knowledge gaps in the various steps and parameters underlying the risk quantification of hydrogen safety.First, a reference case was defined for the benchmark: a virtual hydrogen refuelling station (HRS) in virtual surroundings comprising housing, school, shops and other vulnerable objects. For the study, a two phase approach was followed.In phase 1, all nine partners were requested to conduct a QRA according to their usual approach and experience. Basically, participants were free to define representative release cases, to apply models and frequency assessments according their own methodology, and to present risk according to their usual format. To enable inter-comparison, a required set of results data was prescribed, like distances to specific thermal radiation levels from fires and distances to specific overpressure levels. Moreover, complete documentation of assumptions, base data and references was to be reported.It was not surprising that a wide range of results was obtained, both in the applied approaches as well as in the quantitative outcomes and conclusions. This made it difficult to identify exactly which assumptions and parameters were responsible for the differences in results.These results provided the basis for a more guided QRA, the second phase. This phase 2 was defined in which the QRA was determined by a more limited number of release cases (scenarios). The partners in the project agreed to assess specific scenarios in order to identify the differences in consequence assessment approaches. The results of this phase provide a better understanding of the influence of modelling assumptions and limitations on the eventual conclusions with regard to risk to on-site people and to the off-site public.     

A framework to manage reconfigurability in manufacturing

Nowadays, manufacturing firms are dealing with the unpredictability of market requirements and the frequent changes induced by technological innovation. For this reason, firms are more and more addressing the need to be responsive at an affordable cost. To do so, they are required to develop a capability called reconfigurability. This paper is a review of the existing literature because the current need makes interesting to reflect on the state of the art of reconfigurability as a concept. This reflection has led to focus on reconfigurability characteristics for both their relevance and their relationships with managerial decisions in manufacturing. To this end, a framework has been proposed. It is based on system lifecycle and production levels. These two elements have been deduced from literature and identified as relevant dimensions for decision-making.