Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.     

Development and characterisation of microporous biomimetic scaffolds loaded with magnetic nanoparticles as bone repairing material

Fine-tuning of the scaffolds structural features for bone tissue engineering can be an efficient approach to regulate the specific response of the osteoblasts. Here, we loaded magnetic nanoparticles aka superparamagnetic iron oxide nanoparticles (SPIONs) into 3D composite scaffolds based on biological macromolecules (chitosan, collagen, hyaluronic acid) and calcium phosphates for potential applications in bone regeneration, using a biomimetic approach. We assessed the effects of organic (chitosan/collagen/hyaluronic acid) and inorganic (calcium phosphates, SPIONs) phase over the final features of the magnetic scaffolds (MS). Mechanical properties, magnetic susceptibility and biological fluids retention are strongly dependent on the final composition of MS and within the recommended range for application in bone regeneration. The MS architecture/pore size can be made bespoken through changes of the final organic/inorganic ratio. The scaffolds undertake mild degradation as the presence of inorganic components hinders the enzyme catalytic activity. In vitro studies indicated that osteoblasts (SaOS-2) on MS9 had similar cell behaviour activity in comparison with the TCP control. In vivo data showed an evident development of integration and resorption of the MS composites with low inflammation activity. Current findings suggest that the combination of SPIONs into 3D composite scaffolds can be a promising toolkit for bone regeneration.     

Molecular dynamics simulations of polyphosphazenes: poly[bis(chloro)phosphazene][NPCl2] n

Suitable parameter sets for the CHARMm force field were derived for the structural units in polychlorophosphazene [P=N, P N, P Cl] using the Dinur Hagler energy second derivative procedure based on quantum mechanical SCI calculations using the 6–31G^* basis set. To validate the reliability of the parameter set, structural results obtained with CHARMm for the adopted model compounds (OP₂NCl₅ and OP₃N₂Cl₅) were compared with those derived fromab initio quantum mechanics using the 6–31G^* basis set. Application of molecular dynamics (MD) simulations in combinatioin with the available X-ray diffraction data provided structural and conformational information on the polymer. The calculation made using the periodic boundary conditions (PBC) agree well with the polychlorophosphazene ordered in a monoclinic unit cell (a=5.98,b=12.99,c=4.92 A; β=111.7). This model was stabilized mainly by the image atoms contribution to the electrostatic energy term and had aquasi-planar conformation of the backbone chain (glide symmetry). The MD calculations also provided evidence that the difference between single and double PN bonds is less marked than that measured experimentally. This result is, however, in agreement with more recent and accurate X-ray studies on poly(methylphosphazene). Validation of the polymer model provided a complete picture, otherwise experimentally inaccessible, of the internal fluctuations of the polymeric chains.     

Medium and substitution pattern effects on the action of hydroxyflavones as photoprotectors against singlet molecular oxygen-mediated photooxidation of fats

The ability of mono-, di-, tri-and tetra-hydroxyflavones (7-and 3-hy-droxyflavones, 7, 8-dihydroxyflavone, baicalein and fisetin) to act as photoprotectors against singlet molecular oxygen [O²(Δ_g)]-initiated photooxidation of fats has been established by a kinetic study. The overall quenching rate constants for a series of five hydroxyflavones perfectly parallel their respective behaviour as inhibitors of the sensitized photooxidation of linoleic acid. The best antioxidative effect was exerted by 7-hydroxyflavone which does not chemically react with O²(¹Δ_g). Nevertheless for the remaining flavonoids of the series, the physical deactivation of O²(¹Δ_g) largely prevails over the chemical process. As for the cases of phenols and related hydroxy-aromatic derivatives, the ionization of the -OH group in the flavones, dramatically accelerates the rate of photooxidation. Under these conditions, the 7-hydroxyflavone also reacts effectively with O²(¹Δ_g). Given that flavonoids are natural oil components, this medium effect should be taken into account during the oil-refining process, in order to avoid the flavonoid photodestruction.     

Acidity and catalytic activity of the mesoporous aluminosilicate molecular sieve MCM-41

The acidity and catalytic properties of aluminosilicate mesoporous molecular sieves with the MCM-41 structure and bulk Si/Al ratios in the 10–60 range have been investigated. The incorporation of 4-coordinate aluminium into the structure of MCM-41 generates both BrØnsted and Lewis acid sites in amounts increasing with the degree of incorporation. However, the BrØnsted/Lewis acid population ratio is independent of the content of aluminium. The number and strength of acid sites generated are comparable to those of a pillared acid-activated clay and lower than in zeolite H-Y with Si/Al=3.65. Aluminosilicate MCM-41 is a moderate catalyst for the conversion of cumene which proceeds predominantly via catalytic cracking to propene and benzene. The sample of MCM-41 with the highest content of framework aluminium (Si/Al=10) has the largest number of BrØnsted acid sites and exhibits highest catalytic activity.     

Chemiotropic behavior of female olive fly (Bactrocera oleae GMEL.) onOlea europaea L

An interpretation is given of a number of observations on the chemiotropic behavior ofBactrocera oleae in connection with olive maceration water and the fly's return to the olive groves after the first summer rains. To this end, the headspace of both maceration water and leaf leaching water, simulating rainfall, were examined. In both cases, the presence of ammonia, which is generally known to attract fruit flies (Diptera, Tephritidae), was detected and, for the first time, in addition to other compounds that are inert for the fly, the presence of styrene was also detected. This aromatic hydrocarbon was found to be a strong attractant. It is shown that both ammonia and styrene are products of the metabolism of microbial flora present on the olive and leaf surface.     

Identification of two glutamic acid residues essential for catalysis in the {beta}-glycosidase from the thermoacidophilic archaeon Sulfolobus solfataricus

The Sulfolobus solfataricus, strain MT4, ß-glycosidase(Ssßgly) is a thermophilic member of glycohydrolasefamily 1. To identify active-site residues, glutamic acids 206and 387 have been changed to isosteric glutamine by site-directedmutagenesis. Mutant proteins have been purified to homogeneityusing the Schistosoma japonicum glutathione S-transferase (GST)fusion system. The proteolytic cleavage of the chimeric proteinwith thrombin was only obtainable after the introduction ofa molecular spacer between the GST and the Ssß-glydomains. The Glu387 Gin mutant showed no detectable activity,as expected for the residue acting as the nucleophile of thereaction. The Glu206 Gin mutant showed 10- and 60-fold reducedactivities on aryl-galacto and aryl-glucosides, respectively,when compared with the wild type. Moreover, a significant K_mdecrease with plo-nitrophenyl-ß-D-glucoside was observed.The residual activity of the Glu206 Gln mutant lost the typicalpH dependence shown by the wild type. These data suggest thatGlu206 acts as the general acid/base catalyst in the hydrolysisreaction.     

Densification and Thermal Conductivity of AIN Doped with Y2O3, CaO, and Li2O

Small amounts of Li₂O result in sintering in the AIN-Y₂O₃-CaO and AIN-CaO systems at firing temperatures <1600°C. The effect is ascribed to reduction of the liquidus temperature. Furthermore, Li₂O is removed by volatization at temperatures from 1300° to 1600°C, and its content decreases several ppm from the initial 0.3 wt%. Li₂O-doped AIN specimens containing Y₂O₃ and CaO additives are well densified by firing at 1600°C for 6 h, and their thermal conductivity is 135 W^.m^−1.K⁻¹.The effect of Li₂O addition on sintering and thermal conductivity also is discussed through thermo-dynamic considerations.     

Polydialkylphosphazenes: New synthetic efforts and protonation reactions

Some dialkyl-or diaryl-phosphoranimines are so thermally stable that their thermal polymerization cannot be pursued: it follows that an alternative route to the synthesis of said polymers is to be found. The polymerization ofN-silyldiethylphosphoranimine with the aid of anionic initiators was studied. This reaction. compared with thermal polymerization. proceeded at a lower temperature and with a shorter completion time. Low molecular weights and often bimodal distributions were found.M _m values obtained with Bu₄NF and NaOPh were in the range 1000 10.000, with very narrow polydispersities. Since symmetrical disubstituted polyalkylphosphazenes with alkyl chains from C₂ up to C₈ are insoluble in organic solvents, their solution characterization in usual solvents was prevented. For this purpose, protonation reactions with organic and mineral acids were studied. The protonated polymers were found to be soluble in organic acids and in water, NMR spectra were registered. The molecular weights of the polymers were determined in 20% (v/v) acetic acid. The method, tested on samples of polydimethylphosphazene whose molecular weight was determined independently by membrane osmometry in chloroform solutions, was found to be reliable.Presented at the 1st Italian Workshop on Cyclo- and Polytphosphazene Materials. February 15, 16, 1996, at the CNR Research Area in Padova, Italy.     

Identification of Rare LRP5 Variants in a Cohort of Males with Impaired Bone Mass

Osteoporosis is the most common bone disease characterized by reduced bone mass and increased bone fragility. Genetic contribution is one of the main causes of primary osteoporosis; therefore, both genders are affected by this skeletal disorder. Nonetheless, osteoporosis in men has received little attention, thus being underestimated and undertreated. The aim of this study was to identify novel genetic variants in a cohort of 128 males with idiopathic low bone mass using a next-generation sequencing (NGS) panel including genes whose mutations could result in reduced bone mineral density (BMD). Genetic analysis detected in eleven patients ten rare heterozygous variants within the LRP5 gene, which were categorized as VUS (variant of uncertain significance), likely pathogenic and benign variants according to American College of Medical Genetics and Genomics (ACMG) guidelines. Protein structural and Bayesian analysis performed on identified LRP5 variants pointed out p.R1036Q and p.R1135C as pathogenic, therefore suggesting the likely association of these two variants with the low bone mass phenotype. In conclusion, this study expands our understanding on the importance of a functional LRP5 protein in bone formation and highlights the necessity to sequence this gene in subjects with idiopathic low BMD.