Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl₂ treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.     

Photopolymerization of Epoxy Coatings Containing Iron‐Oxide Nanoparticles

Iron‐oxide nanoparticles were functionalized with epoxy groups and were dispersed into a dicyclo‐aliphatic epoxy resin to obtain organic‐inorganic hybrid coatings via cationic ring‐opening photopolymerization. TEM investigations confirmed that the filler has a size‐distribution range between 5 to 20 nm, without the formation of aggregates. The influence of the presence of Fe₂O₃ on the rate of polymerization was investigated by real time FT‐IR spectroscopy. Increasing the iron‐oxide nanofiller in the photocurable resin induced an increase in the T_g values. By controlling the phase separation it was possible to obtain transparent iron‐oxide nanostructured coatings, characterized by improved hardness.

     

Glycidyl Methacrylate-Based Copolymers as Healing Agents of Waterborne Polyurethanes

Self-healing materials and self-healing mechanisms are two topics that have attracted huge scientific interest in recent decades. Macromolecular chemistry can provide appropriately tailored functional polymers with desired healing properties. Herein, we report the incorporation of glycidyl methacrylate-based (GMA) copolymers in waterborne polyurethanes (WPUs) and the study of their potential healing ability. Two types of copolymers were synthesized, namely the hydrophobic P(BA-co-GMAy) copolymers of GMA with n-butyl acrylate (BA) and the amphiphilic copolymers P(PEGMA-co-GMAy) of GMA with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomer. We demonstrate that the blending of these types of copolymers with two WPUs leads to homogenous composites. While the addition of P(BA-co-GMAy) in the WPUs leads to amorphous materials, the addition of P(PEGMA-co-GMAy) copolymers leads to hybrid composite systems varying from amorphous to semi-crystalline, depending on copolymer or blend composition. The healing efficiency of these copolymers was explored upon application of two external triggers (addition of water or heating). Promising healing results were exhibited by the final composites when water was used as a healing trigger.     

Variants of STAR,AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1

Variants of NR5A1 are often found in individuals with 46,XY disorders of sex development (DSD) and manifest with a very broad spectrum of clinical characteristics and variable sex hormone levels. Such complex phenotypic expression can be due to the inheritance of additional genetic hits in DSD-associated genes that modify sex determination, differentiation and organ function in patients with heterozygous NR5A1 variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the NR5A1 gene. We tested the transactivation activity of novel NR5A1 variants. We additionally included six of these patients in a targeted diagnostic gene panel for DSD and identified a second genetic hit in known DSD-causing genes STAR, AMH and ZFPM2/FOG2 in three individuals. Our study increases the number of NR5A1 variants related to 46,XY DSD and supports the hypothesis that a digenic mode of inheritance may contribute towards the broad spectrum of phenotypes observed in individuals with a heterozygous NR5A1 variation.     

Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.     

An integral planning model that includes production,selling price,cash flow management and flexible capacity

Many authors consider that production and marketing decisions should be integrated. In this paper, we discuss an aggregate planning problem that includes production, selling price, cash management and flexible capacity (by means of hiring and firing and with the possibility of unlimited production subcontracting). The demand is considered to be a nonlinear function of the product selling price. The problem, which is modelled as a mixed integer linear program, can be solved using standard optimisation software. The results of a computational experiment and a numerical example are shown to illustrate the performance of the proposed model and obtain some managerial insights.     

Rheological and electrical percolation thresholds of carbon nanotube/polymer nanocomposites

Percolation thresholds of multiwalled carbon nanotube/polystyrene (MWCNT/PS) nanocomposites (NC) were determined by rheology and electrical conductivity. The percolation threshold found by electrical conductivity was 0.5% carbon nanotubes (CNT) and that by mechanical spectroscopy and relaxation measurements was 0.9% CNT. These results together with those reported in the literature show several types of percolation thresholds, depending on the average filler–filler (CNT and/or aggregates) distance in a polymer matrix. A distance close to polymer gyration radius corresponds to a “soft” rheological threshold (P_{C rheo}^soft). Close contacts between fillers giving rise to a conductive path corresponds to an electrical threshold (P_{C elec}). At high filler concentration, fillers form a network, corresponding to a “rigid” rheological threshold (P_{C rheo}^rigid). These thresholds depend on the filler content and follow the order: P_{C elec}^soft < P_{C elec} < P_{C rheo}^rigid. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers     

Photocatalytic enamel/TiO2 coatings developed by electrophoretic deposition for methyl orange decomposition

The aim of this study was to obtain photocatalytic coatings, capable to decompose organic pollutants, through Electrophoretic Deposition (EPD) of enamels containing respectively 0%, 5%, 10%, 15% (in wt%) of TiO₂ onto carbon steel substrates. High quality and homogeneous coatings were obtained by applying 12.5?V during 10?s, as the best EPD conditions. The layers were subsequently heat treated at 740?°C for 10?min, in order to obtain dense glazes.Rietveld refinement of XRD patterns and Raman results show that, after the heat treatment at 740?°C, TiO₂ mostly exists as anatase, responsible of the photocatalytic effect. Semi-quantitative chemical analysis indicate segregation of TiO₂ on the coatings surface, reaching saturation in the sample with 10?wt% TiO₂. FEG-SEM observations reveal rod-like and spherical Ti-rich phases along the cross section of the coatings; some Ti was also dissolved into the enamel. 3D topographical mapping shows that, by adding TiO₂, surface roughness increases significantly.Photocatalytic tests were carried out using a 2?×?10^?5 M aqueous solution of Methyl Orange (MO) as an organic pollutant. By comparing the decomposition rate of MO achieved with the pure enamel (0% of TiO₂) and with the sample with 10% of TiO₂, it was shown that the addition of 10% of TiO₂ results in 90% photocatalytic efficiency.Moreover, the permeation of organic compounds and their UV degradation were studied by measuring the water contact angle onto the enamel surface directly after dipping into oleic acid and after various UV irradiation times. The longer the UV irradiation time, the lower the contact angle, down to a minimum of 14.54° after 8?h of UV irradiation. This means, the compound was initially adsorbed on the enamel/TiO₂ coating surface (10?wt% TiO₂) but was efficiently decomposed upon UV irradiation.     

Molecular and Electrophysiological Role of Diabetes-Associated Circulating Inflammatory Factors in Cardiac Arrhythmia Remodeling in a Metabolic-Induced Model of Type 2 Diabetic Rat

Background: Diabetic patients have prolonged cardiac repolarization and higher risk of arrhythmia. Besides, diabetes activates the innate immune system, resulting in higher levels of plasmatic cytokines, which are described to prolong ventricular repolarization. Methods: We characterize a metabolic model of type 2 diabetes (T2D) with prolonged cardiac repolarization. Sprague-Dawley rats were fed on a high-fat diet (45% Kcal from fat) for 6 weeks, and a low dose of streptozotozin intraperitoneally injected at week 2. Body weight and fasting blood glucose were measured and electrocardiograms of conscious animals were recorded weekly. Plasmatic lipid profile, insulin, cytokines, and arrhythmia susceptibility were determined at the end of the experimental period. Outward K⁺ currents and action potentials were recorded in isolated ventricular myocytes by patch-clamp. Results: T2D animals showed insulin resistance, hyperglycemia, and elevated levels of plasma cholesterol, triglycerides, TNFα, and IL-1b. They also developed bradycardia and prolonged QTc-interval duration that resulted in increased susceptibility to severe ventricular tachycardia under cardiac challenge. Action potential duration (APD) was prolonged in control cardiomyocytes incubated 24 h with plasma isolated from diabetic rats. However, adding TNFα and IL-1b receptor blockers to the serum of diabetic animals prevented the increased APD. Conclusions: The elevation of the circulating levels of TNFα and IL-1b are responsible for impaired ventricular repolarization and higher susceptibility to cardiac arrhythmia in our metabolic model of T2D.