An Iron Refractory Phenotype in Obese Adipose Tissue Macrophages Leads to Adipocyte Iron Overload

Adipocyte iron overload is a maladaptation associated with obesity and insulin resistance. The objective of the current study was to determine whether and how adipose tissue macrophages (ATMs) regulate adipocyte iron concentrations and whether this is impacted by obesity. Using bone marrow-derived macrophages (BMDMs) polarized to M0, M1, M2, or metabolically activated (MMe) phenotypes, we showed that MMe BMDMs and ATMs from obese mice have reduced expression of several iron-related proteins. Furthermore, the bioenergetic response to iron in obese ATMs was hampered. ATMs from iron-injected lean mice increased their glycolytic and respiratory capacities, thus maintaining metabolic flexibility, while ATMs from obese mice did not. Using an isotope-based system, we found that iron exchange between BMDMs and adipocytes was regulated by macrophage phenotype. At the end of the co-culture, MMe macrophages transferred and received more iron from adipocytes than M0, M1, and M2 macrophages. This culminated in a decrease in total iron in MMe macrophages and an increase in total iron in adipocytes compared with M2 macrophages. Taken together, in the MMe condition, the redistribution of iron is biased toward macrophage iron deficiency and simultaneous adipocyte iron overload. These data suggest that obesity changes the communication of iron between adipocytes and macrophages and that rectifying this iron communication channel may be a novel therapeutic target to alleviate insulin resistance.     

Surface functionalization of bioactive glasses and hydroxyapatite with polyphenols from organic red grape pomace

An extract of polyphenols was obtained from organic red grape pomace, chemically analyzed, and used for functionalization of two bioactive glasses and porous hydroxyapatite. Functionalization is effective on hydroxyapatite and the bioactive glass with higher surface reactivity with a different grafting mechanism. Grafting does not inhibit redox and radical scavenging activity of polyphenols. The grafted polyphenols make a continuous layer with an almost complete surface coverage. Polyphenols are released with different kinetics according to the mechanism of grafting and maintain their redox activity. A homogeneous thin layer of polyphenols is still firmly grafted on both substrates after 28 days of soaking and it still maintains radical scavenging activity. The functionalized samples can be sterilized by gamma irradiation.     

Extraction of polymetallic mineralization information from multispectral Thematic Mapper data using the Gram-Schmidt Orthogonal Projection (GSOP) method

In order to accelerate the reconnaissance of mineral resources in Xingjiang Uygur Autonomous Region of China, multispectral Thematic Mapper (TM) data were used to delineate hydrothermal alteration related to polymetallic mineralization. In addition to the use of commercial image processing packages, new image processing software based on geological environment and spectral information have been developed. The Gram-Schmidt Orthogonal Projection (GSOP) method used in linear algebra for signal processing was adopted for our study. The kernel part of the algorithm is that the GSOP uses least mean square deviation of mathematical expectation in linear vector space (Hilbert space). In a vector space, one base axis is established and other transitional vectors are inputted to evaluate the effectiveness of GSOP. Satisfactory results have been achieved by applying this method to differentiate hydrothermal alterations in the Kangxiwa area of the Kunlun mountains, western China. The red colour in the image shows Pb-Zn-Cu-Au-Ag polymetallic mineralization zones, which were confirmed by field investigations and sample analyses in 1998.     

Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI

Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid and transient decrease in kidney function. AKI is part of an array of conditions collectively defined as acute kidney diseases (AKD). In AKD, persistent kidney damage and dysfunction lead to chronic kidney disease (CKD) over time. A variety of insults can trigger AKI; however, chemotherapy-associated nephrotoxicity is increasingly recognized as a significant side effect of chemotherapy. New biomarkers are urgently needed to identify patients at high risk of developing chemotherapy-associated nephrotoxicity and subsequent AKI. However, a lack of understanding of cellular mechanisms that trigger chemotherapy-related nephrotoxicity has hindered the identification of effective biomarkers to date. In this review, we aim to (1) describe the known and potential mechanisms related to chemotherapy-induced AKI; (2) summarize the available biomarkers for early AKI detection, and (3) raise awareness of chemotherapy-induced AKI.     

Glazing of alumina by a fluoroapatite-containing glass-ceramic

Glazing of alumina substrates was performed in order to prepare bioactive glass-ceramic coatings for biomedical applications. The coating material was a fluoroapatite-containing glass-ceramic (SAF) with a good degree of bioactivity. A careful optimisation of the coating conditions was carried out. The obtained coatings were characterized by means of scanning electron microscopy (SEM), compositional analysis (EDS), X-Ray diffraction (XRD), and in vitro tests (soaking into a simulated body fluid). Direct firing of SAF powders on the ceramic substrates gave unsatisfactory results in terms of crack propagation and bioactivity, due to the nucleation of a non-bioactive Al-rich phase (leucite) with high linear expansion coefficient. The use of an intermediate layer based on a SiO₂-CaO glass (SC) was necessary in order to avoid Al ions diffusion through the coating and thus the formation of undesired additional phases. The coatings obtained with the optimised processing parameters resulted to be adherent, defect-free, and characterized by unchanged composition and structure as well as unmodified bioactivity if compared with the bulk SAF glass-ceramic.     

Bioactivity of degradable polymer sutures coated with bioactive glass

Novel bioactive materials have been prepared by coating violet resorbable Vicryl sutures with a bioactive glass powder derived from a co-precipitation method. Two techniques have been chosen for the composite preparation: pressing the sutures in a bed of glass powder and slurry-dipping of sutures in liquid suspensions of bioactive glass powders. The uniformity and thickness of the coatings obtained by the two methods were compared. The bioactivity of the sutures with and without bioactive glass coating was tested by soaking in an inorganic acellular simulated body fluid (SBF). The composite sutures were characterised by XRD, SEM and FTIR analyses before and after soaking in SBF solution to assess the formation of hydroxyapatite on their surfaces, which is a qualitative measure of their bioactivity. The possible use of bioactive sutures to produce tissue engineering scaffolds and as reinforcement of resorbable calcium phosphates is discussed.     

Beef quality attributes as affected by increasing the intramuscular levels of vitamin E and omega-3 fatty acids

In order to investigate the effects of increasing beef n-3 fatty acid content and the protective effects of vitamin E antioxidant activity on meat quality characteristics, 80 feedlot steers were fed 4 different diets (control, high vitamin E, 10% ground flaxseed or high vitamin E-10% ground flaxseed). While dietary treatments had no effect (P > 0.05) on meat composition or tenderness values, the increase in oxidation products was lower (P = 0.046) in meat from vitamin E supplemented steers and higher (P = 0.006) in meat from flaxseed fed animals. The increase in α-tocopherol tissue levels (P < 0.001) in meat from animals fed flaxseed and increased dietary vitamin E resulted in the lowest drip loss values (P = 0.013). As expected, display time had a large effect on retail traits in both steaks and patties (P < 0.001). While retail traits of steaks were not affected by the dietary treatments (P > 0.05), feeding flaxseed decreased (P < 0.05) ground beef retail scores, which were not corrected by higher levels of dietary vitamin E. Finally, although no effect (P > 0.05) was observed among treatments for sensory attributes in steaks, the correlations of a combined n-3:α-tocopherol ratio against retail and sensory attributes (P < 0.05) suggest that increased n-3 fatty acids levels require increased dietary antioxidants, such as vitamin E to avoid negative effects on meat quality from a loss in oxidative stability.     

Simultaneous Monitoring of Monoclonal Antibody Variants by Strong Cation-Exchange Chromatography Hyphenated to Mass Spectrometry to Assess Quality Attributes of Rituximab-Based Biotherapeutics

Different manufacturing processes and storage conditions of biotherapeutics can lead to a significant variability in drug products arising from chemical and enzymatic post-translational modifications (PTMs), resulting in the co-existence of a plethora of proteoforms with different physicochemical properties. To unravel the heterogeneity of these proteoforms, novel approaches employing strong cation-exchange (SCX) high-performance liquid chromatography (HPLC) hyphenated to mass spectrometry (MS) using a pH gradient of volatile salts have been developed in recent years. Here, we apply an established SCX-HPLC-MS method to characterize and compare two rituximab-based biotherapeutics, the originator MabThera^® and its Indian copy product Reditux™. The study assessed molecular differences between the two drug products in terms of C-terminal lysine variants, glycosylation patterns, and other basic and acidic variants. Overall, MabThera^® and Reditux™ displayed differences at the molecular level. MabThera^® showed a higher degree of galactosylated and sialylated glycoforms, while Reditux™ showed increased levels of oligomannose and afucosylated glycoforms. Moreover, the two drug products showed differences in terms of basic variants such as C-terminal lysine and N-terminal truncation, present in Reditux™ but not in MabThera^®. This study demonstrates the capability of this fast SCX-HPLC-MS approach to compare different drug products and simultaneously assess some of their quality attributes.     

Feasibility, tailoring and properties of polyurethane/bioactive glass composite scaffolds for tissue engineering

This research work aims to propose highly porous polymer/bioactive glass composites as potential scaffolds for hard-tissue and soft-tissue engineering. The scaffolds were prepared by impregnating an open-cells polyurethane sponge with melt-derived particles of a bioactive glass belonging to the SiO₂–P₂O₅–CaO–MgO–Na₂O–K₂O system (CEL2). Both the starting materials and the composite scaffolds were investigated from a morphological and structural viewpoint by X-ray diffraction analysis and scanning electron microscopy. Tensile mechanical tests, carried out according to international ISO and ASTM standards, were performed by using properly tailored specimens. In vitro tests by soaking the scaffolds in simulated body fluid (SBF) were also carried out to assess the bioactivity of the porous composites. It was found that the composite scaffolds were highly bioactive as after 7 days of soaking in SBF a HA layer grew on their surface. The obtained polyurethane/CEL2 composite scaffolds are promising candidates for tissue engineering applications.     

Early stage reactivity and in vitro behavior of silica-based bioactive glasses and glass-ceramics

The surface reactivity of different sets of glasses and glass-ceramics belonging to the SiO₂–P₂O₅–CaO–MgO–K₂O–Na₂O system have been investigated. The attention was focused on the role of their composition on the bioactivity kinetics, in terms of pH modifications, silica-gel formation and its evolution toward hydroxycarbonatoapatite, after different times of soaking in simulated body fluid. Glasses and glass ceramics have been characterized by thermal analysis, SEM-EDS observations and phase analysis (XRD). XPS measurements have been carried out on the most representative set of sample in order to evaluate the evolution of the surface species during the growth of silica-gel and hydroxycarbonatoapatite. The response of murine fibroblast 3T3 to the material before and after a conditioning pre-treatment (immersion in SBF) has been investigated on the same set of samples in order to point out the role of the bioactivity mechanism on cell viability. The main differences among the various glasses have been related to the modifier oxides ratio and to the MgO content, which seems to have an influence on the glass stability, both in terms of thermal properties and surface reactivity. The surface characterization and in vitro tests revealed few variations in the reactivity of the different glasses and glass-ceramics in their pristine form. On the contrary, the different surface properties before and after the pre-treatment in SBF seem to play a role on the biocompatibility of both glass and glass-ceramics, due to the different ion release and hydrophilicity of the surfaces, affecting both cell viability and protein adsorption.