SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc-/- MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc-/- MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc-/- than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc-/- MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc-/- MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

“Ultima Dea”: A Laser Scanner Application for 3D Modelling

This work deals with a novel procedure that can be used for reverse engineering (RE) of big and old boats’ hull through cheap and effective instruments. The procedure has been used to acquire dimensions and shapes of an offshore boat designed by Renato Levi in 1962, named “Ultima Dea”, commissioned by Gianni Agnelli. The research purpose is the development of a method that gives to designers and restorer an “easy to use” instrument for obtaining the 2D and 3D CAD models from a degraded physical object in order to check and re-design the parts to be restored. The study and the application allowed to develop an innovative procedure to set the right acquisition parameters for optimizing the RE output in terms of minimization of maximum error and mean geometric errors between physical object and virtual model, by using a one-shot RE operation and a completely off-line post-processing. This procedure ensures good timesaving, during acquisition, very high reliability level and lightness of CAD models, also being able to reconstruct worn down and spoiled parts (through ex-novo modelling). The procedure shows how the CAD-modelling step can be done directly on graphical models (without surfaces’ mathematics) while ensuring the appropriate level of detail and, contemporarily, improving the interoperability of used and developed software. This procedure is based on the use of well-known methodologies and instruments that usually are employed in architectural relief; finally, it allowed to model the boat’s hull for the redesigning of engine/electrical/services systems and to restore the boat completely

Fuzzy evaluation of temperature distribution in laser sheet metal forming

This paper present a fuzzy inference system for temperature distribution calculation in single pass laser forming of a typical aeronautic alloy. Some experimental and numerical data are used to build the knowledge of the phenomenon, while other nu- merical data are used to check the fuzzy system and to show the precision of the system. The error of fuzzy calculation is less than 5% while the time cal- culation drop down compared to thermal FEM cal- culatio

Diagnostic Enface Imaging of Retinal Vascularization: Topological Reconstruction and Intersection Identification

The work here presented elaborates an analysis of the retinal images, with the aim of characterizing their morphological conformation through the recognition of remarkable parameters such as, among all, the number of vessels, terminal points and bifurcation. The correct identification of each single vessel belonging to the vascular distribution represents a point that has not yet been fully consolidated by the scientific community. The reason lies in the fact that the interpretation of enface images, in which the distribution of the vases is imprinted on a two-dimensional plane, makes it difficult to discern each single section of the vase by following its entire spatial development, due to the multiple overlaps with different pot portions. The aim of this research work is to ensure that the limits encountered in modern retinal image processing algorithms are overcome, through the use of an evaluative comparison of contiguous vessel portions on the basis of local dimensional and intensity similarity criteria. In this way, it is possible to trace the correct attribution of the spatial placement of each vessel, taking it into account in the relative classification in the entire vascular branch of clinical interest