Alkali-bonded SiC based foams

Silicon carbide (SiC) foams were developed by using a low temperature process such as chemical consolidation that is suitable to replace the sintering step. An alkali aluminosilicates binder, also known as geopolymer, was used. It was prepared from metakaolin, as aluminosilicatic raw powder, and KOH/K₂SiO₃ aqueous solution. The foaming agent was the metallic silicon present as impurity in SiC powders. Different grades of SiC were used as the main component (90 wt%) of the foams and the micro and macrostructures varied with the morphologies of the SiC raw powders. The surface of SiC grains participates to the geopolymeric process because of the dissolution of the silica layer into the alkaline solution. SiC foams were tested and characterized under oxidative atmospheres up to 1200 °C.     

The influence of process parameters on in situ inorganic foaming of alkali-bonded SiC based foams

Silicon carbide (SiC) foams were developed with a low temperature process by using an inorganic alkali aluminosilicates binder, also known as geopolymer. The foaming agent was the metallic silicon present as impurity in the SiC powder. Si⁰ in the alkaline solution led to gas evolution that induced the foaming of the slurries. The binder was a geopolymeric resin with atomic ratio Si/Al = 2 and potassium as alkaline cation, classified as (K)poly(silalate-siloxo). The geopolymeric resin was prepared using metakaolin as aluminosilicatic raw powder, while the alkali aqueous solution was KOH/K₂SiO₃. Metakaolin in alkaline conditions dissolved and re-precipitated to form geopolymeric nano-particulates that acted as a glue to stick together SiC particles (90 wt.%). Process parameters such as water addition, mixing time and curing temperature were correlated to the foam structure. The formation of prolate pores induced anisotropy in the compressive strength. The foams were studied by dilatometric analysis in inert and oxidative atmospheres up to 1200 °C.     

Effect of bed material,lignin content,and origin on the processability of biomass in fast pyrolysis reactors

Lignin has great potential for the production of valuable aromatic compounds and has attracted considerable attention. The development of high value applications for Kraft lignin would boost the profitability of pulp and paper operations. A potential solution is the pyrolytic conversion of lignin to valuable liquids and solids. However, Kraft lignin is a thermally sensitive powder which tends to agglomerate under pyrolysis conditions. A mechanically fluidized reactor (MFR) can be used to monitor both the generation of vapours and gas during pyrolysis and how cohesive a feedstock becomes when pyrolyzed. The MFR was, therefore, used to evaluate alternative solutions to improve Kraft lignin behaviour by mixing it with non‐problematic feedstocks or by modifying its bed material. Finally, Kraft lignin behaviour and products were compared to those of hydrolysis lignins from different origins.     

Role of prion protein aggregation in neurotoxicity

In several neurodegenerative diseases, such as Parkinson, Alzheimer's, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.     

4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors

Degradation of the extracellular matrix (ECM) supports tissue integrity and homeostasis, but is also a key factor in cancer metastasis. Heparanase (HPSE) is a mammalian ECM-remodeling enzyme with β-D-endo-glucuronidase activity overexpressed in several malignancies, and is thought to facilitate tumor growth and metastasis. By this virtue, HPSE is considered an attractive target for the development of cancer therapies, yet to date no HPSE inhibitors have progressed to the clinic. Here we report on the discovery of glucurono-configured cyclitol derivatives featuring simple substituents at the 4-O-position as irreversible HPSE inhibitors. We show that these compounds, unlike glucurono-cyclophellitol, are selective for HPSE over β-D-exo-glucuronidase (GUSB), also in platelet lysate. The observed selectivity is induced by steric and electrostatic interactions of the substituents at the 4-O-position. Crystallographic analysis supports this rationale for HPSE selectivity, and computer simulations provide insights in the conformational preferences and binding poses of the inhibitors, which we believe are good starting points for the future development of HPSE-targeting antimetastatic cancer drugs.     

Gene Expression Profiling as a Tool to Investigate the Molecular Machinery Activated during Hippocampal Neurodegeneration Induced by Trimethyltin (TMT) Administration

Trimethyltin (TMT) is an organotin compound exhibiting neurotoxicant effects selectively localized in the limbic system and especially marked in the hippocampus, in both experimental animal models and accidentally exposed humans. TMT administration causes selective neuronal death involving either the granular neurons of the dentate gyrus or the pyramidal cells of the Cornu Ammonis, with a different pattern of localization depending on the different species studied or the dosage schedule. TMT is broadly used to realize experimental models of hippocampal neurodegeneration associated with cognitive impairment and temporal lobe epilepsy, though the molecular mechanisms underlying the associated selective neuronal death are still not conclusively clarified. Experimental evidence indicates that TMT-induced neurodegeneration is a complex event involving different pathogenetic mechanisms, probably acting differently in animal and cell models, which include neuroinflammation, intracellular calcium overload, and oxidative stress. Microarray-based, genome-wide expression analysis has been used to investigate the molecular scenario occurring in the TMT-injured brain in different in vivo and in vitro models, producing an overwhelming amount of data. The aim of this review is to discuss and rationalize the state-of-the-art on TMT-associated genome wide expression profiles in order to identify comparable and reproducible data that may allow focusing on significantly involved pathways.     

Pro- and Anti-Inflammatory Cytokines in the Context of NK Cell–Trophoblast Interactions

During pregnancy, uterine NK cells interact with trophoblast cells. In addition to contact interactions, uterine NK cells are influenced by cytokines, which are secreted by the cells of the decidua microenvironment. Cytokines can affect the phenotypic characteristics of NK cells and change their functional activity. An imbalance of pro- and anti-inflammatory signals can lead to the development of reproductive pathology. The aim of this study was to assess the effects of cytokines on NK cells in the presence of trophoblast cells in an in vitro model. We used TNFα, IFNγ, TGFβ and IL-10; the NK-92 cell line; and peripheral blood NK cells (pNKs) from healthy, non-pregnant women. For trophoblast cells, the JEG-3 cell line was used. In the monoculture of NK-92 cells, TNFα caused a decrease in CD56 expression. In the coculture of NK cells with JEG-3 cells, TNFα increased the expression of NKG2C and NKG2A by NK-92 cells. Under the influence of TGFβ, the expression of CD56 increased and the expression of NKp30 decreased in the monoculture. After the preliminary cultivation of NK-92 cells in the presence of TGFβ, their cytotoxicity increased. In the case of adding TGFβ to the PBMC culture, as well as coculturing PBMCs and JEG-3 cells, the expression of CD56 and NKp44 by pNK cells was reduced. The differences in the effects of TGFβ in the model using NK-92 cells and pNK cells may be associated with the possible influence of monocytes or other lymphoid cells from the mononuclear fraction.     

Inhibition of PKCθ Improves Dystrophic Heart Phenotype and Function in a Novel Model of DMD Cardiomyopathy

Chronic cardiac muscle inflammation and subsequent fibrotic tissue deposition are key features in Duchenne Muscular Dystrophy (DMD). The treatment of choice for delaying DMD progression both in skeletal and cardiac muscle are corticosteroids, supporting the notion that chronic inflammation in the heart plays a pivotal role in fibrosis deposition and subsequent cardiac dysfunction. Nevertheless, considering the adverse effects associated with long-term corticosteroid treatments, there is a need for novel anti-inflammatory therapies. In this study, we used our recently described exercised mdx (ex mdx) mouse model characterised by accelerated heart pathology, and the specific PKCθ inhibitor Compound 20 (C20), to show that inhibition of this kinase leads to a significant reduction in the number of immune cells infiltrating the heart, as well as necrosis and fibrosis. Functionally, C20 treatment also prevented the reduction in left ventricle fractional shortening, which was typically observed in the vehicle-treated ex mdx mice. Based on these findings, we propose that PKCθ pharmacological inhibition could be an attractive therapeutic approach to treating dystrophic cardiomyopathy