The main phenolic compounds responsible for the antioxidant capacity of sweet cherry (Prunus avium L.) pulp

The antioxidant capacity of sweet cherry (Prunus avium L.) pulp extracts is strictly related to the phenolic content, starting from the fact that the higher content of phenolic compounds corresponds to the higher antioxidant indexes. This work aims to assess which compounds characterized three cultivars, namely Ferrovia, Sweetheart, and Lapins grown in Southern Italy and mainly influenced the antioxidant capacity of their extracts. HPLC–MS/MS analyses were conducted to identify and quantify 17 flavonoids and 25 hydroxicinnamates derivatives. A significant influence of cultivar was revealed from one-way MANOVA (p < 0.05). Furthermore, the extracts were tested for their radical scavenging activity (DPPH and ABTS assays) and reducing power using the Folin–Ciocalteau method. Lapins and Sweetheart extracts, richer in phenolic compounds, returned the highest reducing power and radical scavenging capacity. Finally, a Factorial Analysis was applied to the collected data allowing reliable correlations between phenolics and antioxidant indexes

Effect of the curvature and the {\beta} parameter on the nonlinear dynamics of a drift tearing magnetic island

We present numerical simulation studies of 2D reduced MHD equations investigating the impact of the electronic \beta parameter and of curvature effects on the nonlinear evolution of drift tearing islands. We observe a bifurcation phenomenon that leads to an amplification of the pressure energy, the generation of E \times B poloidal flow and a nonlinear diamagnetic drift that affects the rotation of the magnetic island. These dynamical modifications arise due to quasilinear effects that generate a zonal flow at the onset point of the bifurcation. Our simulations show that the transition point is influenced by the \beta parameter such that the pressure gradient through a curvature effect strongly stabilizes the transition. Regarding the modified rotation of the island, a model for the frequency is derived in order to study its origin and the effect of the \beta parameter. It appears that after the transition, an E \times B poloidal flow as well as a nonlinear diamagnetic drift are generated due to an amplification of the stresses by pressure effects

Olive tree in circular economy as a source of secondary metabolites active for human and animal health beyond oxidative stress and inflammation

none10noExtra-virgin olive oil (EVOO) contains many bioactive compounds with multiple biological activities that make it one of the most important functional foods. Both the constituents of the lipid fraction and that of the unsaponifiable fraction show a clear action in reducing oxidative stress by acting on various body components, at concentrations established by the European Food Safety Authority’s claims. In addition to the main product obtained by the mechanical pressing of the fruit, i.e., the EVOO, the residual by-products of the process also contain significant amounts of antioxidant molecules, thus potentially making the Olea europea L. an excellent example of the circular economy. In fact, the olive mill wastewaters, the leaves, the pomace, and the pits discharged from the EVOO production process are partially recycled in the nutraceutical and cosmeceutical fields also because of their antioxidant effect. This work presents an overview of the biological activities of these by-products, as shown by in vitro and in vivo assays, and also from clinical trials, as well as their main formulations currently available on the market.openMallamaci R.; Budriesi R.; Clodoveo M.L.; Biotti G.; Micucci M.; Ragusa A.; Curci F.; Muraglia M.; Corbo F.; Franchini C.Mallamaci, R.; Budriesi, R.; Clodoveo, M. L.; Biotti, G.; Micucci, M.; Ragusa, A.; Curci, F.; Muraglia, M.; Corbo, F.; Franchini, C

A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX\uae) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12\u201316 weeks, and bone regeneration was evaluated by radiography, computed microtomography (\ub5CT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORETEX\uae) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitut

A Tara Gum/Olive Mill Wastewaters Phytochemicals Conjugate as a New Ingredient for the Formulation of an Antioxidant-Enriched Pudding

Olive mill wastewater, a high polyphenols agro-food by-product, was successfully ex-ploited in an eco-friendly radical process to synthesize an antioxidant macromolecule, usefully engaged as a functional ingredient to prepare functional puddings. The chemical composition of lyophilized olive mill wastewaters (LOMW) was investigated by HPLC-MS/MS and1H-NMR analyses, while antioxidant profile was in vitro evaluated by colorimetric assays. Oleuropein aglycone (5.8 μg mL−1) appeared as the main compound, although relevant amounts of an isomer of the 3-hydroxytyrosol glucoside (4.3 μg mL−1) and quinic acid (4.1 μg mL−1) were also detected. LOMW was able to greatly inhibit ABTS radical (IC50 equal to 0.019 mg mL−1), displaying, in the aqueous medium, an increase in its scavenger properties by almost one order of magnitude compared to the organic one. LOMW reactive species and tara gum chains were involved in an eco-friendly grafting reaction to synthesize a polymeric conjugate that was characterized by spec-troscopic, calorimetric and toxicity studies. In vitro acute oral toxicity was tested against 3T3 fibro-blasts and Caco-2 cells, confirming that the polymers do not have any effect on cell viability at the dietary use concentrations. Antioxidant properties of the polymeric conjugate were also evaluated, suggesting its employment as a thickening agent, in the preparation of pear puree-based pudding. High performance of consistency and relevant antioxidants features over time (28 days) were detected in the milk-based foodstuff, in comparison with its non-functional counterparts, confirming LOWM as an attractive source to achieve high performing functional foods

Bioisosteric Modification of To042: Synthesis and Evaluation of Promising Use-Dependent Inhibitors of Voltage-Gated Sodium Channels

Three analogues of To042, a tocainide-related lead compound recently reported for the treatment of myotonia, were synthesized and evaluated in vitro as skeletal muscle sodium channel blockers possibly endowed with enhanced use-dependent behavior. Patch-clamp experiments on hNav1.4 expressed in HEK293 cells showed that N-[(naphthalen-1-yl)methyl]-4-[(2,6-dimethyl)phenoxy]butan-2-amine, the aryloxyalkyl bioisostere of To042, exerted a higher use-dependent block than To042 thus being able to preferentially block the channels in over-excited membranes while preserving healthy tissue function. It also showed the lowest active transport across BBB according to the results of P-glycoprotein (P-gp) interacting activity evaluation and the highest cytoprotective effect on HeLa cells. Quantum mechanical calculations and dockings gave insights on the most probable conformation of the aryloxyalkyl bioisostere of To042 in solution and the target residues involved in the binding, respectively. Both approaches indicated the conformations that might be adopted in both the unbound and bound state of the ligand. Overall, N-[(naphthalen-1-yl)methyl]-4-[(2,6-dimethyl)phenoxy]butan-2-amine exhibits an interesting toxico-pharmacological profile and deserves further investigation

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

Fibroblast Growth Factor-2 Primes Human Mesenchymal Stem Cells for Enhanced Chondrogenesis

Human mesenchymal stem cells (hMSCs) are multipotent cells capable of differentiating into a variety of mature cell types, including osteoblasts, adipocytes and chondrocytes. It has previously been shown that, when expanded in medium supplemented with fibroblast growth factor-2 (FGF-2), hMSCs show enhanced chondrogenesis (CG). Previous work concluded that the enhancement of CG could be attributed to the selection of a cell subpopulation with inherent chondrogenic potential. In this study, we show that FGF-2 pretreatment actually primed hMSCs to undergo enhanced CG by increasing basal Sox9 protein levels. Our results show that Sox9 protein levels were elevated within 30 minutes of exposure to FGF-2 and progressively increased with longer exposures. Further, we show using flow cytometry that FGF-2 increased Sox9 protein levels per cell in proliferating and non-proliferating hMSCs, strongly suggesting that FGF-2 primes hMSCs for subsequent CG by regulating Sox9. Indeed, when hMSCs were exposed to FGF-2 for 2 hours and subsequently differentiated into the chondrogenic lineage using pellet culture, phosphorylated-Sox9 (pSox9) protein levels became elevated and ultimately resulted in an enhancement of CG. However, small interfering RNA (siRNA)-mediated knockdown of Sox9 during hMSC expansion was unable to negate the prochondrogenic effects of FGF-2, suggesting that the FGF-2-mediated enhancement of hMSC CG is only partly regulated through Sox9. Our findings provide new insights into the mechanism by which FGF-2 regulates predifferentiation hMSCs to undergo enhanced CG