The efficacy of islet transplantation is limited by poor graft vascularization. We herein demonstrated that microvesicles (MVs) released from endothelial progenitor cells (EPCs) enhanced human islet ...vascularization. After incorporation into islet endothelium and β-cells, EPC-derived MVs favored insulin secretion, survival, and revascularization of islets transplanted in SCID mice. MVs induced in vitro islet endothelial cell proliferation, migration, resistance to apoptosis, and organization in vessel-like structures. Moreover, MVs partially overcame the antiangiogenic effect of rapamycin and inhibited endothelial–leukocyte interaction via L-selectin and CD40. MVs were previously shown to contain defined patterns of mRNAs. Here we demonstrated that MVs carried the proangiogenic miR-126 and miR-296 microRNAs (miRNAs). MVs pretreated with RNase or derived from Dicer knocked-down EPCs showed a reduced angiogenic effect. In addition, MVs overcame the antiangiogenic effect of the specific antagomiRs of miR-126 and miR-296, suggesting a relevant contribution of miRNAs delivered by MVs to islet endothelium. Microarray analysis of MV-stimulated islet endothelium indicated the upregulation of mRNAs coding for factors involved in endothelial proliferation, differentiation, and angiogenesis. In addition, MVs induced the activation of the PI3K-Akt and eNOS signaling pathways in islet endothelium. These results suggest that MVs activate an angiogenic program in islet endothelium that may sustain revascularization and β-cell function.
The cross-talk between beta cells and endothelium plays a key role in islet physiopathology and in the revascularization process after islet transplantation. However, the molecular mechanisms ...involved in this cross-talk are not fully elucidated. Extracellular vesicles (EVs) are secreted membrane nanoparticles involved in inter-cellular communication through the transfer of proteins and nucleic acids. The aims of this study were: 1) isolation and characterization of EVs from human islets; 2) evaluation of the pro-angiogenic effect of islet-derived EVs on human islet endothelial cells (IECs). EVs were isolated by ultracentrifugation from conditioned medium of human islets and characterized by nanotrack analysis (Nanosight), FACS, western blot, bioanalyzer, mRNA/microRNA RT-PCR array. On IECs, we evaluated EV-induced insulin mRNA transfer, proliferation, resistance to apoptosis, in vitro angiogenesis, migration, gene and protein profiling. EVs sized 236±54 nm, expressed different surface molecules and islet-specific proteins (insulin, C-peptide, GLP1R) and carried several mRNAs (VEGFa, eNOS) and microRNAs (miR-27b, miR-126, miR-130 and miR-296) involved in beta cell function, insulin secretion and angiogenesis. Purified EVs were internalized into IECs inducing insulin mRNA expression, protection from apoptosis and enhancement of angiogenesis. Human islets release biologically active EVs able to shuttle specific mRNAs and microRNAs (miRNAs) into target endothelial cells. These results suggest a putative role for islet-derived EVs in beta cell-endothelium cross-talk and in the neoangiogenesis process which is critical for engraftment of transplanted islets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The renewal policies concerning Medieval castles and noble houses transformed into in palaces and villas, also involve the sub-Alpine territories. In particular, at the end of the 15th century and ...the beginning of the 16th, the main noble dynastic families became carriers of new construction practices aimed at the renovation of existing structures and the opening of new construction sites for palaces and villas outside urban centres and in the countryside. The marquises of Saluzzo encouraged the practice of building new residences in a suburban landscape of great relevance: the palace of Revello, La Morra di Castellar and villa Belvedere constitute an overall project of residences, green areas, both gardens and orchards, which reflect humanist concepts and reinterpret some of the architectural themes of the 'vivere in villa' widespread in central and northern Italy. Other noble families of the territory such as the Tapparelli di Lagnasco and the Saluzzo della Manta built new country houses in which they introduced some of the themes of'all'antica' building such as loggias, galleries and grotesque decorative systems
Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic effects, suggesting that it may play a role in tubular regeneration after acute kidney injury. In this study, elevated ...plasma levels of MSP were found both in critically ill patients with acute renal failure and in recipients of renal allografts during the first week after transplantation. In addition, MSP and its receptor, RON, were markedly upregulated in the regenerative phase after glycerol-induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell proliferation and conferred resistance to cisplatin-induced apoptosis by inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt, and extracellular signal-regulated kinase. MSP also enhanced migration, scattering, branching morphogenesis, tubulogenesis, and mesenchymal de-differentiation of surviving tubular cells. In addition, MSP induced an embryonic phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated during the regeneration of injured tubular cells, and it exerts multiple biologic effects that may aid recovery from acute kidney injury.
Urbino, Rome, Florence, Milan, Ferrara... but also Mantua and Imola, Carpi and Saluzzo, Naples and Sicily: a collection of case studies on the Renaissance renewal of Italian court palaces from a ...comparative perspective.
The European project called “PER VIAM Pilgrims’ Routes In Action”, funded by the European Commission in 2012, is a significant opportunity of cultural and economic development for the whole Europe ...and also for the territory of Piedmont Region. The certainty of the need for transnational cooperation, which should create a network amongst the different territories in a perspective of working together and exchange of traveling, economic and cultural experiences – as well as best practices - nowadays calls for implementation tools such as European projects supported and sought for by the local authorities.The Piedmont is nowadays crossed by various cultural itineraries, many of which are certificated by the European Council: Via Francigena, the Route of the Cistercian Abbeys, the Transromanica, the itinerary of the historical thermal cities and the Saint Michael's way. Starting from a survey on the meaning of "cultural itinerary" expressed by the different European institutions (i.e. ICOMOS, UNESCO, Council of Europe and European Commission), this essay is proposing an analysis of the current status of such territory, highlighting the public policies in progress, the role and activities of the local associations and the valorisation of implemented projects as related to those itineraries which have already been recognized by the Council of Europe.This paper presents some significant experiences and best practices in the study of religious tourism, as they have been defined on the regional territory throughout the last few years, which can contribute to the debate and to the overall awareness on management and valorization of sustainable tourism.
The international debate on resilience has grown around the ability of a community to prepare for and adapt to natural disasters, with a growing interest in holistically understanding complex ...systems. Although the concept of resilience has been investigated from different perspectives, the lack of understanding of its conceptual comprehensive aspects presents strong limitations for spatial planning and for the adoption of policies and programs for its measurement and achievement. In this paper, we refer to “territorial resilience” as an emerging concept capable of aiding the decision-making process of identifying vulnerabilities and improving the transformation of socio-ecological and technological systems (SETSs). Here, we explore the epistemology of resilience, reviewing the origins and the evolution of this term, providing evidence on how this conceptual umbrella is used by different disciplines to tackle problem-solving that arises from disaster management and command-control practices to augment the robustness. Assuming the SETSs paradigm, the seismic and structural engineering, social sciences and history, urban planning and climatology perspectives intersects providing different analytical levels of resilience, including vulnerability and patrimony from a community and cultural perspective. We conclude that territorial resilience surpasses the analytical barriers between different disciplines, providing a useful concept related to complex problem-solving phenomena for land use planning, opening a new research question: how can territorial resilience be measured, acknowledging different units and levels of analysis aiding decision-making in spatial plans and projects? In attempting to understand a resilient system, quantitative and qualitative measurements are crucial to supporting planning decisions.
Abstract Background The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome. Methods We retrospectively studied 35 kidney ...transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined. Results Of the 35 patients with dnDSA and TG, 15 (42.9%) had C1q-positive dnDSA and 20 (57.1%) had C1q-negative dnDSA. Ten out of 15 patients with C1q-positive dnDSA (66.6%) and 5 with C1q-negative dnDSA (25%) had C4d positive staining renal biopsies (P = 0.02), being the C1q-negative dnDSA/C4d-negative TG 42.9% of the total. The C1q-positive dnDSA group has significantly higher IgG DSA Class II MFI than the C1q-negative dnDSA group (P = 0.004). Patients with C4d deposits have significantly higher IgG DSA MFI for both Class I and Class II than those without C4d deposits (P = 0.02). We found a trend toward higher graft loss in the C1q-positive dnDSA group (60%) versus the C1q-negative dnDSA group (40%) without a statistical significance (P = 0.31). Conclusion Our study provides further characterization of TG associated with dnDSA. The major part of dnDSA-associated TG was C1q-negative and the presence of C1q-fixing dnDSA did not significantly correlate with graft outcome.
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