Hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (αs1-, β- and k-casein) after enzymatic hydrolysis with pepsin and enzymatic extract from Pleurotus eryngii

The aim of this study was to estimate the hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (α_s1-, β- and k-casein) after in vitro digestion with two different enzymatic systems: pepsin from porcine gastric mucosa (EP) and a crude enzymatic extract from the edible mushroom Pleurotus eryngii. The used enzymes showed a different mode of casein catalysis with a consequent production of peptides of different antioxidant activity. The CN haplotype significantly influenced peptides production; in fact, the amino acid substitutions caused by genetic polymorphisms at the α_s1-, β- and k-CN loci influenced the sites of enzymatic cleavage and therefore the produced peptides. The above is evidenced by the different antioxidant activity found in the hydrolysates depending on the used enzymatic system, the CN haplotype, and the CN haplotype × enzymatic treatment interaction. The findings of this study are a perspective for the production of specific foods that exert a biological effect in addition to the nutritional one.     

Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted.     

Carbon nanotubes play an important role in the spatial arrangement of calcium deposits in hydrogels for bone regeneration

Age related bone diseases such as osteoporosis are considered among the main causes of reduced bone mechanical stability and bone fractures. In order to restore both biological and mechanical function of diseased/fractured bones, novel bioactive scaffolds that mimic the bone structure are constantly under development in tissue engineering applications. Among the possible candidates, chitosan-based thermosensitive hydrogel scaffolds represent ideal systems due to their biocompatibility, biodegradability, enhanced antibacterial properties, promotion of osteoblast formation and ease of injection, which makes them suitable for less invasive surgical procedures. As a main drawback, these chitosan systems present poor mechanical performance that could not support load-bearing applications. In order to produce more mechanically-competent biomaterials, the combined addition of hydroxyapatite and carbon nanotubes (CNTs) is proposed in this study. Specifically, the aim of this work is to develop thermosensitive chitosan hydrogels containing stabilised single-walled and multi-walled CNTs, where their effect on the mechanical/physiochemical properties, calcium deposition patterns and ability to provide a platform for the controlled release of protein drugs was investigated. It was found that the addition of CNTs had a significant effect on the sol–gel transition time and significantly increased the resistance to compression for the hydrogels. Moreover, in vitro calcification studies revealed that CNTs played a major role in the spatial arrangements of newly formed calcium deposits in the composite materials studied, suggesting that they may have a role in the way the repair of fragile and/or fractured bones occurs in vivo.     

Inhibition of colon adenocarcinoma cell proliferation by flavonols is linked to a G2/M cell cycle block and reduction in cyclin D1 expression

The moderate consumption of red wine has been proposed to reduce the incidence of colorectal cancer. Its anti-cancer action my in part be mediated by the actions of polyphenols on colon cancer epithelial cells. We show that a red wine phenolic (50 μg/ml) extract devoid of anthocyanins (removed to reflect polyphenol bioavailability to the large intestine) and the major red wine flavonols quercetin, myricetin, laricitrin and syringetin (50 μM) are capable of inhibiting the proliferation of colorectal epithelial adenocarcinoma cells. This anti-proliferative activity was partly mediated by the direct cytotoxic actions of flavonols and also their ability to cause a significant cell cycle blockage in G2/M. The anti-proliferative effects induced by flavonols were preceded, in most cases, by a strong and significant reduction of cyclooxygenase-2 (COX-2) and cyclin D1 expression. These results indicate that the observed inverse correlation between colon cancer and a moderate red wine intake may be partly mediated by the actions of red wine flavonols on the growth of cancer cells.     

Transition Metal‐Free Direct C?H (Hetero)arylation of Heteroarenes: A Sustainable Methodology to Access (Hetero)aryl‐Substituted Heteroarenes

In recent years, environmental and economic reasons have motivated the development of transition metal‐free carbon‐carbon bond forming reactions and some excellent reviews have covered this research area of particular interest for the pharmaceutical industry. However, none of these reviews has been specifically dedicated to summarize and discuss the results achieved in the rapidly growing field of the transition metal‐free direct (hetero)arylation reactions of heteroarenes. This review, which covers the literature from 2008 to 2014, aims to provide a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes and biheteroaryls via transition metal‐catalyzed reactions.

     

Digital light processing stereolithography of hydroxyapatite scaffolds with bone-like architecture,permeability, and mechanical properties

This work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam-like ceramic scaffolds by using three-dimensional (3D) micro-tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer-by-layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly-porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100-800 µm) replicating the 3D open-cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75-1.74 × 10⁻⁹ m², which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]-based stereolithography) shows great promise for the development of porous bioceramics with bone-like architecture and mass transport properties.     

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non-cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid ¹³C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched ¹³C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.     

Perceived shrinkage of motion paths.

We show that human observers strongly underestimate a linear or circular trajectory that a luminous spot follows in the dark. At slow speeds, observers are relatively accurate, but, as the speed increases, the size of the path is progressively underestimated, by up to 35%. The underestimation imposes little memory load and does not require tracking of the trajectory. Most importantly, we found that underestimation occurred only when successive motion vectors changed in direction. This suggests a perceptual rather than representational origin of the illusion, related to vector-sum integration over time of neural motion signals in different directions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mass spectrometric contributions to problems related to the chemistry of atmospheres

Recent mass spectrometric studies of species and processes relevant to the chemistry of atmospheres are reported. New species have been detected, including HO(3); a stratospheric reservoir of OH radicals; the [H(2)O(+)O(2)(-)] charge transfer complex, central to the atmospheric photonucleation theory; and the OSOSO oxide and its cation, likely present in the Io's atmosphere. As to ionic processes, a new route to tropospheric N(2)O in air ionized by lightning and coronas is reported, as well as the complex chemistry promoted by ionization of ozone/freon and ozone/carbonyl sulfide mixtures and the formation of O(5)(+), relevant to the problem of (18)O excess in stratospheric ozone.