Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

Neural Computing and Applications - In this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble...     

Aromatic bisphenol A-based elastomers via hydrosilylation chemistry

The preparation of highly aromatic elastomers from a bisphenol A-based divinyl-terminated resin and polymerization with various aromatic silane containing compounds utilizing a room temperature hydrosilylation reaction is demonstrated. The polymers exhibit high thermal and oxidative stability with 5% weight losses around 430 and 350°C and char yields ranging from 35% to 40%. The thermosets maintained their elastomeric properties with good hardness and mechanical properties as measured by elongation measurements. The toughness of the thermosets was not improved with the inclusion of aromatic moieties but the hardness did appear to increase with the addition of more aromatic groups.     

Influence of ethanol/water ratio in ultrasound and high‐pressure/high‐temperature phenolic compound extraction from agri‐food waste

The valorisation and management of agri‐food waste are currently hot investigation topics which probe the recovery of valuable compounds, such as polyphenols. In this study, high‐pressure/high‐temperature extraction (HPTE) and ultrasound‐assisted extraction (UAE) have been used to study the recovery of phenolic compounds from grape marc and olive pomace in hydroalcoholic solutions. The main phenolic compounds in both extracts were identified by HPLC‐DAD. Besides extraction yield (total polyphenol and flavonoid content) and the antiradical power, polyphenol degradation under HPTE and UAE has also been studied. HPTE with ethanol 75% gave higher phenolic extraction yields: 73.8 ± 1.4 mg of gallic acid equivalents per gram of dried matter and 60.0 mg of caffeic acid equivalents per gram of dried matter for grape marc and olive pomace, respectively. In this study, the efficient combination of ethanol/water mixture with HPTE or UAE has been used to enhance the recovery of phenolic compounds from grape marc and olive pomace. HPLC‐DAD showed that UAE prevents phenolic species degradation damage because of its milder operative conditions.     

Commiphora myrrha (Nees) Engl. extracts: evaluation of antioxidant and antiproliferative activity and their ability to reduce microbial growth on fresh‐cut salad

With the aim to develop natural preservatives displaying also chemopreventive activity, different Commiphora myrrha (Nees) Engl. extracts were studied. Myrrh essential oils, obtained by steam distillation and microwave‐assisted hydrodistillation, and several other extracts, obtained by sequential procedures with petroleum ether (PE), ethanol, ethyl acetate and butanol, have been screened for their antioxidant (DPPH· scavenging assay) and antiproliferative activity (on both nontumour and colon cancer cell lines) without previous purification. Considering that the colon cancer cell lines were more sensitive to PE and ethanol extracts, the latter of which showed the highest antioxidant activity (EC50 = 0.160 ± 0.008 mg mL^?1), both have been selected for further antibacterial/antifungal activity tests using an antimicrobial diffusion test and a growth inhibition test on salads. Results showed that the ethanol extract possessed the higher antibacterial and antifungal activity. Compared to untreated product, fresh‐cut salads treated with these two myrrh extracts displayed a significant lower bacterial growth. Although further investigation is required, these promising results offer hints as how to improve the shelf life of fresh‐cut salad.     

Astringency sub-qualities of red wines and the influence of wine–saliva aggregates

Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication.     

A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.