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...     

The properties of electroactive ruthenium oxide coatings supported by titanium-based ternary carbides

Electroactive oxide coatings on titanium, known in industrial chlorine production as dimensionally stable anodes (DSA), are of limited service life owing to the dissolution of active oxide, but also due to low corrosion stability of titanium, at high anodic potentials and elevated temperatures. In order to improve the anode stability, ternary carbide, Ti₃SiC₂, could be a promising material for the coating support, since chemical corrosion stability of Ti₃SiC₂ is significantly higher if compared to Ti. In this work, the possibility of the sol-gel preparation of RuO₂-TiO₂ coating on Ti₃SiC₂ is investigated and comparison of the basic characteristics of sol-gel processed oxide coating, Ru_0.5Ti_0.5O₂, applied onto Ti₃SiC₂ and Ti, is reported. Microscopic investigation of the coating surface showed that considerably less cracked coating is formed onto the Ti₃SiC₂ support. Slightly higher voltammetric currents are registered for Ti₃SiC₂-supported coating in H₂SO₄ and NaCl solution. The activity for chlorine evolution is higher, while the currents of oxygen evolution reaction are lower for Ru_0.5Ti_0.5O₂/Ti₃SiC₂ anode in comparison to Ru_0.5Ti_0.5O₂/Ti anode. Even though these preliminary results on the basic electrochemical properties of Ru_0.5Ti_0.5O₂/Ti₃SiC₂ anode and chemical stability of Ti₃SiC₂ are promising, the accelerated stability test in NaCl solution showed that coated Ti₃SiC₂ is not anodically stable and lasts considerably shorter than Ru_0.5Ti_0.5O₂/Ti anode prepared and tested under the same conditions.     

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.     

Role of Tunneling Nanotubes in the Nervous System

Cellular communication and the transfer of information from one cell to another is crucial for cell viability and homeostasis. During the last decade, tunneling nanotubes (TNTs) have attracted scientific attention, not only as a means of direct intercellular communication, but also as a possible system to transport biological cargo between distant cells. Peculiar TNT characteristics make them both able to increase cellular survival capacities, as well as a potential target of neurodegenerative disease progression. Despite TNT formation having been documented in a number of cell types, the exact mechanisms triggering their formation are still not completely known. In this review, we will summarize and highlight those studies focusing on TNT formation in the nervous system, as well as their role in neurodegenerative diseases. Moreover, we aim to stress some possible mechanisms and important proteins probably involved in TNT formation in the nervous system.     

TMEM106B Acts as a Modifier of Cognitive and Motor Functions in Amyotrophic Lateral Sclerosis

The transmembrane protein 106B (TMEM106B) gene is a susceptibility factor and disease modifier of frontotemporal dementia, but few studies have investigated its role in amyotrophic lateral sclerosis. The aim of this work was to assess the impact of the TMEM106B rs1990622 (A–major risk allele; G–minor allele) on phenotypic variability of 865 patients with amyotrophic lateral sclerosis. Demographic and clinical features were compared according to genotypes by additive, dominant, and recessive genetic models. Bulbar onset was overrepresented among carriers of the AA risk genotype, together with enhanced upper motor neuron involvement and poorer functional status in patients harboring at least one major risk allele (A). In a subset of 195 patients, we found that the homozygotes for the minor allele (GG) showed lower scores at the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen, indicating a more severe cognitive impairment, mainly involving the amyotrophic lateral sclerosis-specific cognitive functions and memory. Moreover, lower motor neuron burden predominated among patients with at least one minor allele (G). Overall, we found that TMEM106B is a disease modifier of amyotrophic lateral sclerosis, whose phenotypic effects encompass both sites of onset and functional status (major risk allele), motor functions (both major risk and minor alleles), and cognition (minor allele).     

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.