The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis

Vascular calcification correlates with inflammation and plaque instability in a dual manner, depending on the spotty/granular (micro) or sheet-like/lamellated (macro) pattern of calcification. Modified lipoproteins trigger both inflammation and calcification via receptors for advanced lipoxidation/glycation endproducts (ALEs/AGEs). This study compared the roles of galectin-3 and receptor for AGEs (RAGE), two ALEs/AGEs-receptors with diverging effects on inflammation and bone metabolism, in the process of vascular calcification. We evaluated galectin-3 and RAGE expression/localization in 62 human carotid plaques and its relation to calcification pattern, plaque phenotype, and markers of inflammation and vascular osteogenesis; and the effect of galectin-3 ablation and/or exposure to an ALE/AGE on vascular smooth muscle cell (VSMC) osteogenic differentiation. While RAGE co-localized with inflammatory cells in unstable regions with microcalcification, galectin-3 was expressed also by VSMCs, especially in macrocalcified areas, where it co-localized with alkaline phosphatase. Expression of galectin-3 and osteogenic markers was higher in macrocalcified plaques, whereas the opposite occurred for RAGE and inflammatory markers. Galectin-3-deficient VSMCs exhibited defective osteogenic differentiation, as shown by altered expression of osteogenic transcription factors and proteins, blunted activation of pro-osteoblastogenic Wnt/β-catenin signalling and proliferation, enhanced apoptosis, and disorganized mineralization. These abnormalities were associated with RAGE up-regulation, but were only in part prevented by RAGE silencing, and were partially mimicked or exacerbated by treatment with an AGE/ALE. These data indicate a novel molecular mechanism by which galectin-3 and RAGE modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by modulating Wnt/β-catenin signalling, and independently of ALEs/AGEs

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid Response (AAR) and the Unfolded Protein Response (UPR) pathways. Lack of ASNS protein expression is a hallmark of Acute Lymphoblastic Leukemia (ALL) blasts, which, therefore, are auxotrophic for Asn. This peculiarity is the rationale for the use of bacterial L-Asparaginase (ASNase) for ALL therapy, the first example of anti-cancer treatment targeting a tumor-specific metabolic feature. Other hematological and solid cancers express low levels of ASNS and, therefore, should also be Asn auxotrophs and ASNase sensitive. Conversely, in the last few years, several reports indicate that in some cancer types ASNS is overexpressed, promoting cell proliferation, chemoresistance, and a metastatic behavior. However, enhanced ASNS activity may constitute a metabolic vulnerability in selected cancer models, suggesting a variable and tumor-specific role of the enzyme in cancer. Recent evidence indicates that, beyond its canonical role in protein synthesis, Asn may have additional regulatory functions. These observations prompt a re-appreciation of ASNS activity in the biology of normal and cancer tissues, with particular attention to the fueling of Asn exchange between cancer cells and the tumor microenvironment

Structural distinctions of Fe2O3-In2O3 composites obtained by various sol-gel procedures, and their gas-sensing features

New and various approaches to the sol–gel synthesis of advanced gas-sensing materials based on nanosized Fe2O3–In2O3 (9:1 mol) mixed oxides, which differ in phase composition and grain size, have been considered in this paper. The correlation between the structural features of the composites and their gas-sensing behavior has been established. It was found that multi-phase Fe2O3–In2O3 composites containing metastable -Fe2O3 structure are characterized by the greatest sensitivity to both reducing (C2H5OH) and oxidizing (NO2) gases tested in this paper. The influence of synthesis conditions on the structural peculiarities of the Fe2O3–In2O3 composites was studied in detail and the possibility to adjust fine structure of the materials was demonstrated

Acute occlusion of descending thoracic aorta

Acute aortic occlusion is a rare but potentially devastating clinical event, which requires a prompt diagnosis and emergency treatment. Only 5 cases of native thoracic aorta acute occlusion have so far been reported with different pathologic causes. The clinical features depend on the level of occlusion. Sometimes the diagnosis could be misinterpreted as a stroke or other diseases of the central nervous system. This could lead to a delay in the diagnosis and revascularization procedure, followed by a morbidity or mortality increase. Open surgery has been considered the first-line approach. This study is of a female patient suffering from acute descending thoracic aorta occlusion undergoing, for the first time to our knowledge, endovascular surgical treatment

Oligodendroglioma cells lack glutamine synthetase and are auxotrophic for glutamine, but do not depend on glutamine anaplerosis for growth

In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth

Development of glass-stalks-unsaturated polyester hybrid composites

The aim of this study is to investigate the possibility to use agro-residues of the vinification process as a cheaper and eco-friendly fillers to prepare unsaturated polyester composites for interior design building sector. Experimental unsaturated polyester–based resin composite samples, reinforced with grape stalks, were prepared by a simple casting technique. The glass microspheres were added in the mixing to increase the mechanical and physical properties of the final materials. A silane coupling agent was used to increase the interface adhesion between resin and grape stalks. The samples were subjected to several tests. Unfilled samples were analyzed by Differential Scanning calorimetry (DSC). Prepared silanized and non-silanized composites were completely characterized in order to study the effect of stalk fibers concentration on the mechanical, chemical and physical properties. The results showed that mechanical and physical properties for silanized composites were superior to non-silanized composites. The presence of stalks, up to 50% wt. increased Young's Modulus preserving a satisfactory tensile strength and hardness in comparison with the neat resin properties. Then, the final results showed that grape stalks from winemaking can be satisfactory used as natural filler resource to produce composites for interior furniture