Drug Release from Lipogels According to Gelling Conditions and Mechanical Treatment

The release rate of a drug dissolved in the liquid phase of lipogels may be greatly affected by the type and concentration of gelling agent and by processing conditions and mechanical treatment of the ointment. These differences in release rate are reduced after application of mechanical stress comparable with the strain exerted on the ointment during application to the skin. Therefore, changes in the concentration of gelling agents used to achieve suitable consistency and manufacturing and packing processes that meet industrial and marketing requirements do not appear to exert a practical influence on drug availability after application to the skin.     

Notch Signaling Regulation in Autoinflammatory Diseases

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.     

Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping

Systematic characterisation of the reactivity of the lysine moieties in CRM₁₉₇ towards N‐hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two‐step conjugation of various glycans to CRM₁₉₇ by click chemistry in a well‐defined manner. By semiquantitative LC‐MS/MS analysis of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational analysis of the solvent accessibility of each lysine residue (based on the CRM₁₉₇ crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the preparation of lysine‐mediated glycoconjugates with improved batch‐to‐batch reproducibility, thereby producing neo‐glycoconjugates with more‐consistent biological activity.     

Na-feldspar (F) and kaolinite (K) system at high temperature: Resulting phase composition,micro-structural features and mullite-glass Gibbs energy of formation,as a function of F/K ratio and kaolinite crystallinity

The system Na-feldspar (F) and kaolinite (K) was investigated at temperatures of interest in ceramic applications (1200–1280 °C) to study the effects of F/K ratios by weight and crystallinity degree of kaolinite on the final product, micro-structural features and mullite-glass Gibbs energy of formation (ΔG^eff). Mullite and glass are the dominant phases; in general, the higher the temperature, the larger the former. An F/K increase promotes the formation of glass and secondary mullite, appearing along with the primary one. ΔG^eff was modelled by α(T) × (F/K)² + β(T) × F/K + γ(T), α, β and γ being linear functions of temperature whose coefficients were determined by fitting the ΔG^eff-theoretical to the ΔG^eff-obtained from the measured phase compositions. ΔG^eff is less affected by temperature than by F/K, whose increase shifts equilibrium towards glass phases. The ΔG^eff-curves for ordered and disordered kaolinite intersect one another at F/K ～0.5, a ratio close to that used in industrial practice.     

Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes

Notch signaling has been identified as a critical regulator of cartilage development and homeostasis. Its pivotal role was established by both several joint specific Notch signaling loss of function mouse models and transient or sustained overexpression. NOTCH1 is the most abundantly expressed NOTCH receptors in normal cartilage and its expression increases in osteoarthritis (OA), when chondrocytes exit from their healthy “maturation arrested state” and resume their natural route of proliferation, hypertrophy, and terminal differentiation. The latter are hallmarks of OA that are easily evaluated in vitro in 2-D or 3-D culture models. The aim of our study was to investigate the effect of NOTCH1 knockdown on proliferation (cell count and Picogreen mediated DNA quantification), cell cycle (flow cytometry), hypertrophy (gene and protein expression of key markers such as RUNX2 and MMP-13), and terminal differentiation (viability measured in 3-D cultures by luminescence assay) of human OA chondrocytes. NOTCH1 silencing of OA chondrocytes yielded a healthier phenotype in both 2-D (reduced proliferation) and 3-D with evidence of decreased hypertrophy (reduced expression of RUNX2 and MMP-13) and terminal differentiation (increased viability). This demonstrates that NOTCH1 is a convenient therapeutic target to attenuate OA progression.     

Photoprotective Role of Photosynthetic and Non-Photosynthetic Pigments in Phillyrea latifolia: Is Their “Antioxidant” Function Prominent in Leaves Exposed to Severe Summer Drought?

Carotenoids and phenylpropanoids play a dual role of limiting and countering photooxidative stress. We hypothesize that their “antioxidant” function is prominent in plants exposed to summer drought, when climatic conditions exacerbate the light stress. To test this, we conducted a field study on Phillyrea latifolia, a Mediterranean evergreen shrub, carrying out daily physiological and biochemical analyses in spring and summer. We also investigated the functional role of the major phenylpropanoids in different leaf tissues. Summer leaves underwent the most severe drought stress concomitantly with a reduction in radiation use efficiency upon being exposed to intense photooxidative stress, particularly during the central hours of the day. In parallel, a significant daily variation in both carotenoids and phenylpropanoids was observed. Our data suggest that the morning-to-midday increase in zeaxanthin derived from the hydroxylation of ß-carotene to sustain non-photochemical quenching and limit lipid peroxidation in thylakoid membranes. We observed substantial spring-to-summer and morning-to-midday increases in quercetin and luteolin derivatives, mostly in the leaf mesophyll. These findings highlight their importance as antioxidants, countering the drought-induced photooxidative stress. We concluded that seasonal and daily changes in photosynthetic and non-photosynthetic pigments may allow P. latifolia leaves to avoid irreversible photodamage and to cope successfully with the Mediterranean harsh climate.     

A comprehensive investigation of dye–chitosan blended films for green chemistry applications

In this paper, the ability of chitosan film to remove dyestuff from wastewater was evaluated for environmental applications, using three commercial direct azo dyes. Two chitosan films were adopted: the standard one prepared following a well‐known procedure to form it, and a novel one, with a weakly acidic character. Moreover, to improve the adsorption process, the hydrophobic character of the films was investigated. The pH of the dye solutions was also changed, showing an excellent ability in dye removal at pH 12. The films were characterized by means of spectroscopic and morphologic methods to better understand the nature of interactions between dyes and chitosan chains. Swelling ratio measurements were also performed. All analyses suggest that all dyes showed a strong affinity to chitosan polymer chains, with the presence of extended hydrogen bonds and Van der Waals forces perturbing the chitosan network. Interestingly, very good results were obtained in recycling experiments related to the dyeing capacities of chitosan blended films in the presence of textiles. An ecofriendly application is thus presented in this paper. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45945.     

Crack-free caustic magnesia-bonded refractory castables

A growing interest in designing high-alumina MgO-bonded refractory castables has been identified in recent years due to the magnesia ability to react: (i) with water at the initial processing stages of these materials (inducing the precipitation of brucite phase) or (ii) with alumina, giving rise to in situ MgAl₂O₄ generation at high temperatures. Nevertheless, despite the great potential of caustic magnesia to be used as a binder in such systems due to its high reactivity, it is still a challenge to control the hydration reaction rate of this oxide and the negative effects derived from the expansive feature of Mg(OH)₂ formation. Thus, this work evaluated the incorporation of different contents of aluminum hydroxyl lactate (AHL) into caustic magnesia-bonded castables, aiming to control the brucite precipitation during the curing and drying steps of the prepared samples, resulting in crack-free refractories. The designed compositions were characterized via flowability, setting behavior, X-ray diffraction, cold flexural strength, porosity, permeability and thermogravimetric measurements. According to the results, instead of Mg(OH)₂, hydrotalcite-like phases [Mg₆Al₂(OH)₁₆(OH)₂.4.5H₂O and Mg₆Al₂(OH)₁₆(CO₃)·4H₂O] were the main hydrated phases identified in the AHL-containing compositions. The addition of 1.0 wt% of aluminum hydroxyl lactate to the designed castable proved to be, so far, the best option for this magnesia source, resulting in the development of a crack-free refractory with enhanced properties and greater spalling resistance under heating.