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.     

The Effect of Electrospun Gelatin Fibers Alignment on Schwann Cell and Axon Behavior and Organization in the Perspective of Artificial Nerve Design

Electrospun fibrous substrates mimicking extracellular matrices can be prepared by electrospinning, yielding aligned fibrous matrices as internal fillers to manufacture artificial nerves. Gelatin aligned nano-fibers were prepared by electrospinning after tuning the collector rotation speed. The effect of alignment on cell adhesion and proliferation was tested in vitro using primary cultures, the Schwann cell line, RT4-D6P2T, and the sensory neuron-like cell line, 50B11. Cell adhesion and proliferation were assessed by quantifying at several time-points. Aligned nano-fibers reduced adhesion and proliferation rate compared with random fibers. Schwann cell morphology and organization were investigated by immunostaining of the cytoskeleton. Cells were elongated with their longitudinal body parallel to the aligned fibers. B5011 neuron-like cells were aligned and had parallel axon growth when cultured on the aligned gelatin fibers. The data show that the alignment of electrospun gelatin fibers can modulate Schwann cells and axon organization in vitro, suggesting that this substrate shows promise as an internal filler for the design of artificial nerves for peripheral nerve reconstruction.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.     

Bijective Linear Time Coding and Decoding for k-Trees

The problem of coding labeled trees has been widely studied in the literature and several bijective codes that realize associations between labeled trees and sequences of labels have been presented. k-trees are one of the most natural and interesting generalizations of trees and there is considerable interest in developing efficient tools to manipulate this class of graphs, since many NP-Complete problems have been shown to be polynomially solvable on k-trees and partial k-trees. In 1970 Rényi and Rényi generalized the Prüfer code, the first bijective code for trees, to a subset of labeled k-trees. Subsequently, non redundant codes that realize bijection between k-trees (or Rényi k-trees) and a well defined set of strings were produced. In this paper we introduce a new bijective code for labeled k-trees which, to the best of our knowledge, produces the first coding and decoding algorithms running in linear time with respect to the size of the k-tree.     

Effect of Oil Phase Lipophilicity on In Vitro Drug Release from O/W Microemulsions with Low Surfactant Content

ABSTRACT

In this work we investigated the effects of oil phase lipophilicity on in vitro drug release from topical o/w microemulsions (MEs) containing low percentages of emulsifiers. Three different lipids, isopropyl myristate (IPM), isopropyl palmitate (IPP), and isopropyl stearate (IPS), whose lipophilicity increased in the order IPM < IPP <IPS, were used as oil phase to prepare o/w MEs containing low amounts (7.7% w/w) of two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (5:2) (MEs 1–3) and oleth-20/glyceryl oleate (5:2) (MEs 4–6). All the MEs were prepared using the phase inversion temperature (PIT) method.

Three active compounds (0.5% w/w), Naproxen (NAP), Idebenone (IDE), and Butylmethoxydibenzoylmethane (BMBM), were selected as model drugs and their release rates from PIT MEs were evaluated using Franz-type diffusion cells. All the MEs gave a mean droplet diameter ranging from 28 to 44 nm and showed a single peak in size distribution. The addition of IDE to MEs 1–6 did not significantly change ME droplet size. On the contrary, an increase of the droplet size beyond the ME limit (150 nm) was observed when isoceteth-20 was used as surfactant to prepare MEs containing NAP or MEs containing BMBM and IPS as oil phase. Pseudo-first order release rates were observed only for NAP from MEs 1–3, while MEs containing IDE showed an initial slow release followed by an increased release of the test compound. The release rate constants were found to be dependent on the ME composition and on the active compound incorporated. The highest release rate was observed from ME 1 containing IPM as oil phase and NAP as drug. As regards BMBM, its release rate was not calculated since no release was observed until 6 h from the beginning of the experiment. The cumulative amount of active compound released after 22 h was inversely related to drug lipophilicity (NAP Log P = 2,9; IDE Log P 3,5; BMBM Log P 4,8). These findings could be attributable to a reduced thermodynamic activity of the drugs in the vehicles containing the most lipophilic oil phase due to an increase of drug solubility which could lead to an unfavorable drug partition from the oil phase. The results of this study suggest that the choice of proper combinations of oil phase lipids and emulsifiers may allow achieving drug controlled delivery from topical o/w MEs with low emulsifier content.     

Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis

A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein.