Valutazioni economiche dei processi estrattivi e di valorizzazione dei reflui oleari.

The technological innovations of the project VALOROLIO act as an integrated package of interventions at the system load of extra virgin olive oil extraction and treatment processes of all products with a view to their economic value. The pitting of the olives allows a substantial modification of the extraction process with the production of new products, almond and peanut, as well as the modification of the quali-quantitative traditional products (virgin olive residues pitted, vegetation waters rich in polyphenols) which guarantee pet food uses and pharmaceutical. The economic unit in the course of the project assessed the economic effects of innovation on the entire supply chain by identifying the critical points is that the business opportunities. Here, the limited space available, will be presented the microeconomic analysis documenting the opportunities offered by technological innovation

Valutazioni economiche dei processi estrattivi e di valorizzazione dei reflui oleari.

The technological innovations of the project VALOROLIO act as an integrated package of interventions at the system load of extra virgin olive oil extraction and treatment processes of all products with a view to their economic value. The pitting of the olives allows a substantial modification of the extraction process with the production of new products, almond and peanut, as well as the modification of the quali-quantitative traditional products (virgin olive residues pitted, vegetation waters rich in polyphenols) which guarantee pet food uses and pharmaceutical. The economic unit in the course of the project assessed the economic effects of innovation on the entire supply chain by identifying the critical points is that the business opportunities. Here, the limited space available, will be presented the microeconomic analysis documenting the opportunities offered by technological innovation

A polymorphism in the human serotonin 5-HT2A receptor gene may protect against systemic sclerosis by reducing platelet aggregation

Introduction: Platelet aggregation may contribute to the pathogenesis of systemic sclerosis: following activation, platelets release significant amounts of serotonin - which promotes vasoconstriction and fibrosis, and further enhances aggregation. The C+1354T polymorphism in the exonic region of the serotonin 2A receptor gene determining the His452Tyr substitution was associated with blunted intracellular responses after serotonin stimulation, and may have a role in susceptibility to scleroderma. Methods: One hundred and fifteen consecutive systemic sclerosis patients and 140 well-matched healthy control individuals were genotyped by sequence-specific primer-PCR for the His452Tyr substitution of the serotonin 2A receptor gene, and associations were sought with scleroderma and its main clinical features. The functional relevance of the His452Tyr substitution was also assessed by evaluating the aggregation of platelet-rich plasma from His452/ His452 and His452/Tyr452 healthy individuals after stimulation with adenosine diphosphate ± serotonin. Results: The T allele of the C+1354T polymorphism was underrepresented in scleroderma patients compared with control individuals (5.2% versus 12.4%, P < 0.001, chi-square test and 1,000-fold permutation test) and its carriage reduced the risk for systemic sclerosis (odds ratio = 0.39, 95% confidence interval = 0.19 to 0.85, P < 0.01). Platelets from His452/Tyr452 healthy subjects more weakly responded to serotonin stimulation compared with platelets from His452/His452 individuals (3.2 ± 2.6-fold versus 9.6 ± 8.6-fold increase in aggregation, P = 0.017 by Kolmogorov-Smirnov test and P = 0.003 after correction for baseline adenosine diphosphate-induced aggregation values). Conclusion: The His452Tyr substitution may influence susceptibility to systemic sclerosis by altering platelet aggregation in response to serotonin

Ultrastructural characterization of calcification onset and progression in subdermally implanted aortic valves. Histochemical and spectrometric data

Detailed characterization of the subdermal model is a significant tool for better understanding of calcification mechanisms occurring in heart valves. In previous ultrastructural investigation on six-week-implantated aortic valve leaflets, modified pre-embedding glutaraldehyde-cuprolinic-blue reactions (GA-CB) enabled sample decalcification with concurrent retention/staining of lipid-containing polyanionic material, which lined cells and cell-derived matrix-vesicle-like bodies (phthalocyanin-positive layers: PPLs) co-localizing with the earliest apatite nucleation sites. Additional post-embedding silver staining (GA-CB-S) revealed PPLs to contain calcium-binding sites. This investigation concerns valve leaflets subjected to shorter implantation times to shed light on the modifications associated with PPLs generation and calcification onset/progression. Spectrometric estimations revealed time-dependent calcium increase, for unreacted samples, and copper modifications indicating an increase in acidic, non-glycanic material, for GA-CB-reacted samples. Two-day-implant thin sections showed emission and subsequent reabsorption of lamellipodium-like protrusions by cells, originating ECM-containing vacuoles, and/or degeneration stages characterized by the appearance of GA-CB-S-reactive, organule-derived dense bodies and progressive dissolution of all cell membranes. In one-week-implants, the first PPL-lined cells were found to co-exist with cells where GA-CB-S-reactive material accumulated, or exudated towards their edges, or outcropped at the ECM milieu, so acquiring PPL features. PPL-derived material was observed increasingly to affect the ECM on thin sections of one-week- to six-week-implants. These results show an endogenous source for PPLs and reveal that a peculiar cascade of cell degenerative steps is associated with valve mineralization in the subdermal model, providing new useful parameters for more reliable comparison of this experimental calcification process versus the physiological and pathological processes

Dorsomorphin reverses the mesenchymal phenotype of breast cancer initiating cells by inhibition of bone morphogenetic protein signaling

Increasing evidence supports the theory that tumor growth, homeostasis, and recurrence are dependent on a small subset of cells with stem cell properties, redefined cancer initiating cells (CICs) or cancer stem cells. Bone morphogenetic proteins (BMPs) are involved in cell-fate specification during embryogenesis, in the maintenance of developmental potency in adult stem cells and may contribute to sustain CIC populations in breast carcinoma. Using the mouse A17 cell model previously related to mesenchymal cancer stem cells and displaying properties of CICs, we investigated the role of BMPs in the control of breast cancer cell plasticity. We showed that an autocrine activation of BMP signaling is crucial for the maintenance of mesenchymal stem cell phenotype and tumorigenic potential of A17 cells. Pharmacological inhibition of BMP signaling cascade by Dorsomorphin resulted in the acquisition of epithelial-like traits by A17 cells, including expression of Citokeratin-18 and E-cadherin, through downregulation of Snail and Slug transcriptional factors and Cyclooxygenase-2 (COX2) expression, and in the loss of their stem-features and self-renewal ability. This phenotypic switch compromised A17 cell motility, invasiveness and in vitro tumor growth. These results reveal that BMPs are key molecules at the crossroad between stemness and cancer

Corrigendum to "Mechanisms of responsiveness to and resistance against trabectedin in murine models of human myxoid liposarcoma" [Genomics Volume 113, Issue 5, September 2021, Pages 3439–3448]

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Involvement of cytosolic phospholipase A2 alpha in pathological and experimental cardiovascular mineralization

Cytosolic phospholipase A2 alpha (cPLA2a) is a calcium-dependent enzyme constitutively expressed by most human cells catalyzing the hydrolysis of membrane glycerophospholipids bearing arachidonic acid at the sn-2 position with production of downstream pro-inflammatory lipid mediators (Murakami and Kudo, 2002). Although cPLA2a seems to facilitate the release of pro-calcific matrix vesicles by hypertrophic chondrocytes during ossification (Wuthier et al., 1977), its involvement in pathological biomineralization has not yet been elucidated. Here, cPLA2a expression was assessed in the context of both pathological and experimentally induced mineralization affecting cardiovascular tissues and cultured aortic valve interstitial cells (AVICs). cPLA2a resulted to be expressed by fibroblasts, smooth muscle cells, macrophages, and activated endothelium populating both calcified aortic valves and atherosclerotic aorta walls. cPLA2a was also expressed by cultured AVICs, with enzyme expression rate correlating with mineralization rate, being enhanced by inflammation and high phosphate concentrations. For all calcific contexts, ultrastructural examination revealed mineralization to depend on progressive accumulation and release of acidic lipids, acting as major hydroxyapatite nucleators, followed by cell disgregation into a multitude of particles having calcium nucleation capability, according to peculiar degenerative patterns as those previously described (Ortolani et al., 2010). In conclusion, enzyme expression and ultrastructural patterns being shared by both pathological and experimental calcific conditions suggests that cPLA2a might be actually involved in the etiopathogenesis of cardiovascular mineralization, besides representing a potential target for novel therapeutic strategies aimed to counteract the progression of cardiovascular calcific diseases

Involvement of cytosolic phospholipase A2 alpha in pathological and experimental cardiovascular mineralization

Cytosolic phospholipase A2 alpha (cPLA2a) is a calcium-dependent enzyme constitutively expressed by most human cells catalyzing the hydrolysis of membrane glycerophospholipids bearing arachidonic acid at the sn-2 position with production of downstream pro-inflammatory lipid mediators (Murakami and Kudo, 2002). Although cPLA2a seems to facilitate the release of pro-calcific matrix vesicles by hypertrophic chondrocytes during ossification (Wuthier et al., 1977), its involvement in pathological biomineralization has not yet been elucidated. Here, cPLA2a expression was assessed in the context of both pathological and experimentally induced mineralization affecting cardiovascular tissues and cultured aortic valve interstitial cells (AVICs). cPLA2a resulted to be expressed by fibroblasts, smooth muscle cells, macrophages, and activated endothelium populating both calcified aortic valves and atherosclerotic aorta walls. cPLA2a was also expressed by cultured AVICs, with enzyme expression rate correlating with mineralization rate, being enhanced by inflammation and high phosphate concentrations. For all calcific contexts, ultrastructural examination revealed mineralization to depend on progressive accumulation and release of acidic lipids, acting as major hydroxyapatite nucleators, followed by cell disgregation into a multitude of particles having calcium nucleation capability, according to peculiar degenerative patterns as those previously described (Ortolani et al., 2010). In conclusion, enzyme expression and ultrastructural patterns being shared by both pathological and experimental calcific conditions suggests that cPLA2a might be actually involved in the etiopathogenesis of cardiovascular mineralization, besides representing a potential target for novel therapeutic strategies aimed to counteract the progression of cardiovascular calcific diseases

Pro-calcific responses by aortic valve interstitial cells in a novel in vitro model simulating dystrophic calcification

Etiopathogenetic mechanisms in calcific aortic valve stenosis are still poorly understood despite this being the third major cause of heart disease in western world. In prior in vitro cultures simulating metastatic calcification, pro&shy;calcific effects on aortic valve interstitial cells (AVICs) resulted by adding bacterial endotoxin lipopolysaccharide (LPS) at high inorganic phosphate (Pi) levels. Here we accomplished improved in vitro models simulating either metastatic (Pi = 2.6 mM) or dystrophic calcification (Pi = 1.3 mM), in which LPS&shy;stimulated bovine AVICs underwent extra-stimulation with macrophage-cytokine-containing media derived from paral&shy; lel cultures of allogeneic monocyte/macrophages in turn stimulated with LPS. In dystrophic calcification-like cultures, lower calcium amount was spectrometrically assessed with parallel reduced alkaline phosphatase activity with respect to metastatic calcification&shy;like cultures, with an about three&shy;fold slower progression of mineralization. Hydroxyapatite crystal precipitation was ultrastructurally found to correlate with AVIC degeneration processes culminating with the formation of phthalocyanin-positive lipidic layers (PPLs) at the surface of cells and cell-derived matrix-vesicle-like bodies, acting as calcium nucleators according to a pattern mirroring those we had previously found in in vivo conditions. In conclusion, an in vitro model has been devel&shy; oped enabling reliable simulations of the effects exerted on AVICs by putatively pro- or anti-calcific agents