91 research outputs found

    Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis.

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    Caveolae, the flask-shaped membrane invaginations abundant in endothelial cells, have acquired a prominent role in signal transduction. Evidence, that events occurring in caveolae participate in cell survival and angiogenesis, has been recently substantiated by the identification of two novel caveolar constituents: prostacyclin synthase (PGIS) and the cellular form of prion protein (PrPc). We have shown that PGIS, previously described as an endoplasmic reticulum component, is bound to caveolin-1 (cav-1) and localized in caveolae in human endothelial cells. By generating prostacyclin, PGIS is involved in angiogenesis. Previous observations regarding the localization of PrPc in caveolae-like membrane domains (CLDs) have been recently confirmed and extended. It has been demonstrated that PrPc is bound to cav-1 and, by recruiting Fyn kinase, can participate in signal transduction events connected to cell survival and differentiation. The new entries of PGIS and PrPc in caveolar components place caveolae and CLDs at the centre of a network, where cells decide whether to proliferate or differentiate and whether to survive or to suicide by apoptosis. © 2002 Elsevier Science Inc. All rights reserved

    Substantial overview on mesenchymal stem cell biological and physical properties as an opportunity in translational medicine

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    Mesenchymal stem cells (MSC) have piqued worldwide interest for their extensive potential to treat a large array of clinical indications, their unique and controversial immunogenic and immune modulatory properties allowing ample discussions and debates for their possible applications. Emerging data demonstrating that the interaction of biomaterials and physical cues with MSC can guide their differentiation into specific cell lineages also provide new interesting insights for further MSC manipulation in different clinical applications. Moreover, recent discoveries of some regulatory molecules and signaling pathways in MSC niche that may regulate cell fate to distinct lineage herald breakthroughs in regenerative medicine. Although the advancement and success in the MSC field had led to an enormous increase in the amount of ongoing clinical trials, we still lack defined clinical therapeutic protocols. This review will explore the exciting opportunities offered by human and animal MSC, describing relevant biological properties of these cells in the light of the novel emerging evidence mentioned above while addressing the limitations and challenges MSC are still facing

    CERAMIC FOAMS FROM PRECERAMIC POLYMER AND POLYURETHANE: PREPARATION AND MORPHOLOGICAL INVESTIGATIONS

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    Open-cell ceramic foams were obtained from a preceramic polymer (silicone resin) and blown polyurethanes. The preceramic polymer, which is crosslinked by condensation of silanol groups, was dissolved in CH2Cl2 and added to a liquid polyol containing the surfactant and the amine catalyst. Isocyanate was then added to the mixture and the foam was obtained through a twofold blowing mechanism (physical and chemical blowing). The morphology of the expanded polyurethane, which can be flexible or semirigid, characterized the final structure of the ceramic foam. The materials obtained were pyrolyzed in a nitrogen flux at temperatures of 1000-1200 degrees C, thus allowing for the polymer-to-ceramic transformation to occur in the preceramic polymer. The ceramic foams produced in this way consisted of an amorphous silicon oxycarbide ceramic (SiOC). They presented a density ranging from 0.1 to 0.3 g/cm(3) The average pore diameter ranged from 200 to 400 mu m and they possessed 80 to 90 % open porosity

    Effects of heavy-ion strikes on fully depleted SOI MOSFETs with ultra-thin gate oxide and different strain-inducing techniques

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    We study the immediate and long-term effects of heavy-ion strikes on 65-nm Fully Depleted SOI MOSFETs with different strain engineering solutions. Some of the phenomena already present in bulk devices, such as drain current collapse, are still observed alongside some new long-term effects concerning the degradation kinetics under electrical stress. On the other side, early breakdown seems to vanish. SOI degradation after heavy-ion strikes and during following electrical stress is shown to depend on the strain level and strain-inducing technique. We interpreted these results in terms of radiation-induced defects in the gate and isolation oxide

    RNA interference as a key to knockdown overexpressed cycloxygenase 2 gene in tumour cells

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    Silencing those genes that are overexpressed in cancer and contribute to the survival and progression of tumour cells is the aim of several researches. Cyclooxygenase-2 (COX-2) is one of the most intensively studied genes since it is overexpressed in most tumours, mainly in colon cancer. The use of specific COX-2 inhibitors to treat colon cancer has generated great enthusiasm. Yet, the side effects of some inhibitors emerging during long-term treatment have caused much concern. Genes silencing by RNA interference (RNAi) has led to new directions in the field of experimental oncology. In this study, we detected sequences directed against COX-2 mRNA, that potently downregulate COX-2 gene expression and inhibit phorbol 12-myristate 13-acetate-induced angiogenesis in vitro in a specific, nontoxic manner. Moreover, we found that the insertion of a specific cassette carrying anti-COX-2 short hairpin RNA sequence into a viral vector (pSUPER.retro) greatly increased silencing potency in a colon cancer cell line (HT29) without activating any interferon response. Phenotypically, COX-2 deficient HT29 cells showed a significant impairment of their in vitro malignant behaviour. Thus, the retroviral approach enhancing COX-2 knockdown, mediated by RNAi, proved to be an useful tool to better understand the role of COX-2 in colon cancer. Furthermore, the higher infection efficiency we observed in tumour cells, if compared to normal endothelial cells, may disclose the possibility to specifically treat tumour cells without impairing endothelial COX-2 activit

    Caveolae and caveolae constituents in mechanosensing: effect of modelled microgravity on cultured human endothelial cells.

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    Studies in modeled microgravity or during orbital space flights have clearly demonstrated that endothelial cell physiology is strongly affected by the reduction of gravity. Nevertheless, the molecular mechanisms by which endothelial cells may sense gravity force remain unclear. We previously hypothesized that endothelial cell caveolae could be a mechanosensing system involved in hypergravity adaptation of human endothelial cells. In this study, we analyzed the effect on the physiology of human umbilical vein endothelial cell monolayers of short exposure to modeled microgravity (24-48 h) obtained by clinorotation. For this purpose, we evaluated the levels of compounds, such as nitric oxide and prostacyclin, involved in vascular tone regulation and synthesized starting from caveolae-related enzymes. Furthermore, we examined posttranslational modifications of Caveolin (Cav)-1 induced by simulated microgravity. The results we collected clearly indicated that short microgravity exposure strongly affected endothelial nitric oxide synthase activity associated with Cav-1 (Tyr 14) phosphorylation, without modifying the angiogenic response of human umbilical vein endothelial cells. We propose here that one of the early molecular mechanisms responsible for gravity sensing of endothelium involves endothelial cell caveolae and Cav-1 phosphorylation

    EBEI: A new index of eye bank efficiency

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    purpose: to describe a new proxy of the eye bank (EB) activity named “eye bank efficiency Index” (EBEI), calculated as the ratio between the number of corneal tissues distributed by an EB within a certain time period, and the difference between the number of procured and discarded tissues. methods: to demonstrate the effectiveness of the new metric as compared to traditional statistics, an analysis was conducted using data from the largest Italian eye bank (fondazione banca degli occhi del veneto venice, Italy). collected data included: the number of corneas retrieved, the number of discarded grafts, and the number of distributed tissues. the analysis focused on three defined timeframes: January to december, march to may (the “Italian Lockdown period”), and June to december (the “Italian post-lockdown period”). results: In 2020, the annual variation of the EBEI showed a significant increase of up to 3.4% compared to the previous year (0.986 in 2019; 1.020 in 2020), but then gradually decreased to 0.993 in 2022. however, during the months of lockdown in 2020, there was a significant decline of −13.8% in the EBEI compared to the same period in the previous year. the variation in the EBEI during the post-lockdown months was minimal in 2020 and 2021, with the lowest EBEI value of 0.976 being reached in 2022 (−7.8% compared to 2019). conclusion: the EBEI is a simple and reliable new measure of the EB activity. Its widespread adoption could ensure a more accurate and reliable analysis of EB data for academic, political, and economic purposes
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