Adjusting Some Properties of Poly(methacrylic acid) (Nano)Composite Hydrogels by Means of Silicon-Containing Inorganic Fillers

The present work aims to show how the main properties of poly(methacrylic acid) (PMAA) hydrogels can be engineered by means of several silicon-based fillers (Laponite XLS/XLG, montmorillonite (Mt), pyrogenic silica (PS)) employed at 10 wt% concentration based on MAA. Various techniques (FT-IR, XRD, TGA, SEM, TEM, DLS, rheological measurements, UV-VIS) were used to comparatively study the effect of these fillers, in correlation with their characteristics, upon the structure and swelling, viscoelastic, and water decontamination properties of (nano)composite hydrogels. The experiments demonstrated that the nanocomposite hydrogel morphology was dictated by the way the filler particles dispersed in water. The equilibrium swelling degree (SDe) depended on both the pH of the environment and the filler nature. At pH 1.2, a slight crosslinking effect of the fillers was evidenced, increasing in the order Mt < Laponite < PS. At pH > pKa_MAA (pH 5.4; 7.4; 9.5), the Laponite/Mt-containing hydrogels displayed a higher SDe as compared to the neat one, while at pH 7.4/9.5 the PS-filled hydrogels surprisingly displayed the highest SDe. Rheological measurements on as-prepared hydrogels showed that the filler addition improved the mechanical properties. After equilibrium swelling at pH 5.4, G’ and G” depended on the filler, the Laponite-reinforced hydrogels proving to be the strongest. The (nano)composite hydrogels synthesized displayed filler-dependent absorption properties of two cationic dyes used as model water pollutants, Laponite XLS-reinforced hydrogel demonstrating both the highest absorption rate and absorption capacity. Besides wastewater purification, the (nano)composite hydrogels described here may also find applications in the pharmaceutical field as devices for the controlled release of drugs.     

Molecular Genetics of GLUT1DS Italian Pediatric Cohort: 10 Novel Disease-Related Variants and Structural Analysis

GLUT1 deficiency syndrome (GLUT1DS1; OMIM #606777) is a rare genetic metabolic disease, characterized by infantile-onset epileptic encephalopathy, global developmental delay, progressive microcephaly, and movement disorders (e.g., spasticity and dystonia). It is caused by heterozygous mutations in the SLC2A1 gene, which encodes the GLUT1 protein, a glucose transporter across the blood-brain barrier (BBB). Most commonly, these variants arise de novo resulting in sporadic cases, although several familial cases with AD inheritance pattern have been described. Twenty-seven Italian pediatric patients, clinically suspect of GLUT1DS from both sporadic and familial cases, have been enrolled. We detected by trios sequencing analysis 25 different variants causing GLUT1DS. Of these, 40% of the identified variants (10 out of 25) had never been reported before, including missense, frameshift, and splice site variants. Their structural mapping on the X-ray structure of GLUT1 strongly suggested the potential pathogenic effects of these novel disease-related mutations, broadening the genotypic spectrum heterogeneity found in the SLC2A1 gene. Moreover, 24% is located in a vulnerable region of the GLUT1 protein that involves transmembrane 4 and 5 helices encoded by exon 4, confirming a mutational hotspot in the SLC2A1 gene. Lastly, we investigated possible correlations between mutation type and clinical and biochemical data observed in our GLUT1DS cohort, revealing that splice site and frameshift variants are related to a more severe phenotype and low CSF parameters.     

The Inhibition of the Inducible Nitric Oxide Synthase Enhances the DPSC Mineralization under LPS-Induced Inflammation

Nitric oxide (NO) is a key messenger in physiological and pathological processes in mammals. An excessive NO production is associated with pathological conditions underlying the inflammation response as a trigger. Among others, dental pulp inflammation results from the invasion of dentin by pathogenic bacteria. Vital functions of pulp mesenchymal stem cells (DPSCs, dental pulp stem cells), such as mineralization, might be affected by the inducible NOS (iNOS) upregulation. In this context, the iNOS selective inhibition can be considered an innovative therapeutic strategy to counteract inflammation and to promote the regeneration of the dentin-pulp complex. The present work aims at evaluating two acetamidines structurally related to the selective iNOS inhibitor 1400W, namely CM544 and FAB1020, in a model of LPS-stimulated primary DPSCs. Our data reveal that CM544 and even more FAB1020 are promising anti-inflammatory compounds, decreasing IL-6 secretion by enhancing CD73 expression-levels, a protein involved in innate immunity processes and thus confirming an immunomodulatory role of DPSCs. In parallel, cell mineralization potential is retained in the presence of compounds as well as VEGF secretion, and thus their angiogenetic potential. Data presented lay the ground for further investigation on the anti-inflammatory potential of acetamidines selectively targeting iNOS in a clinical context.     

The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

Evolution of phenols and pigments in extra virgin olive oil from irrigated super‐intensive orchard

Phenolic compounds have a high importance in olive oil because of their effect on shelf life and sensory properties. This study reports on the HPLC profiles of the phenolic compounds of virgin olive oils obtained from Arbequina olives from the harvesting in a super‐intensive orchard under a linear irrigation system. In addition, phenolic content, carotenoid and chlorophyllic pigments, and oxidative stability were analyzed. Total phenol content and 3,4‐DHPEA‐EDA increased up to a maximum throughout the ripening process. The simple phenols tyrosol and hydroxytyrosol acetate increased throughout the ripening process, however, there was not found a clear trend in hydroxytyrosol content. Minor constituents such as vanillic acid and p‐coumaric acid increased up to a maximum and then decreased, since vanillin decreased progressively throughout the time of harvest. 3,4‐DHPEA‐EDA and lignans were present in considerable amounts in the studied samples, while oleuropein aglycone was present in a low amount. Total phenol content and oil stability followed the same trend throughout the study, so a very good correlation was established between them. Total secoiridoids and, specifically, 3,4‐DHPEA‐EDA seemed to be responsible for oil stability. The pigment content decreased during ripening, and not a positive correlation was found between pigments and oil stability. Practical applications : The results can be used to determine the best time for harvesting in order to obtain olive oils with different phenols and pigment contents. This is important for sensory characteristics of the olive oils and also for olive oil stability.     

Physicochemical and Bioactive Compounds of ‘Cantaloupe’ Melon: Effect of Ozone Processing on Pulp and Seeds

Melon seeds are an important source of bioactive compounds, which are considered to be health beneficial. Therefore, the objective of this work was to assess the impact of gaseous ozone treatments (30 and 60 min) on melon seeds paste (nonedible part) and compare with the effect on pulp (edible part). Ozone treatments were evaluated in terms of physicochemical (color, pH, and soluble solids content) and nutritional profiles (total phenolics, total carotenoids, and total antioxidant capacity) of processed material. Results indicate that ozone has a different impact on the two fruit matrices, being seeds less affected by this preservation treatment.     

Microwave-Hydrothermal Synthesis of Nanophase Ferrites

This paper reports the synthesis of technologically important ferrites such as ZnFe₂O₄, NiFe₂O₄, MnFe₂O₄, and CoFe₂O₄ by using novel microwave-hydrothermal processing. Nanophase ferrites with high surface areas, in the range of 72-247m²/g, have been synthesized in a matter of a few minutes at temperatures as low as 164°C. The rapid synthesis of nanophase ferrites via an acceleration of reaction rates under microwave-hydrothermal conditions is expected to lead to energy savings.     

Enhancements in sugar immobilization in polymeric macroporous matrices for affinity capture

The use of macroporous monolithic matrices in the purification of biocompounds is constantly growing and developing. In this work, the objective was to optimize the quantity of N-acetyl-D-glucosamine (D-GlcNAc) immobilized on the surface of macroporous polymeric cryogels for capture of lectins from less clarified solutions. Surface response methodology was applied and it was observed that the immobilization temperature of the glutaraldehyde (GLU) and the D-GlcNAc concentration influenced the amount of sugar immobilized. The matrices produced with 1.1% of allyl glycidyl ether were functionalized by GLU. Optimal maximum condition was obtained with mean value of 160.39 ± 26.38 mg of D-GlcNAc immobilized per gram of dry cryogel. Characterization analyses of the matrices showed that the activation process was effective, maintaining the macroporous structure and physical characteristics. The adsorbents produced were tested for capture of lectins from a crude protein solution of barley. At tested conditions, adsorbent capture around 11% of protein in solution but reduce the hemaglutinating capacity in 40%, demonstrating its selectivity. The cryogels functionalized with D-GlcNAc present potential for use in capture compounds by affinity with carbohydrates, such as lectins. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47956.