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.     

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.     

A life cycle approach to Green Public Procurement of building materials and elements: A case study on windows

Green Public Procurement (GPP) is a significant policy tool for reducing the environmental impacts of services and products throughout their whole life cycle. Scientific and easily verifiable environmental criteria, based on a life cycle approach, should be developed and used within procurement procedures. In this paper, Life Cycle Assessment (LCA) is applied to wood windows showing how it can support the criteria definition. After a foreword on GPP development in Italy, the evaluation features of the environmental performances of building materials and components are outlined. The LCA case study is then presented, describing the use of the analysis results to define the environmental criteria. LCA allowed to identify the main impacts and the critical processes of the window life cycle, giving a scientific framework to discuss GPP criteria with manufacturers associations and stakeholders. Nevertheless, it couldn’t help neither in identifying detailed criteria for GPP nor to define numerical thresholds to be used as reference in procurement procedures. The appropriate strategies should be selected taking into account the technical status of the market, the standard development and the voluntary industry commitments, involving manufacturers associations. Finally, some elements to develop a structured approach for GPP of construction materials are presented.     

A GC-EI-MS/MS Method for the Determination of 15 Polybrominated Diphenyl Ethers (PBDEs) in Fish and Shellfish Tissues

This paper describes the development and validation of an analytical method to determine 15 polybrominated diphenyl ethers (PBDEs) in fish and shellfish tissues with gas chromatography coupled to triple quadrupole mass spectrometry using electron impact source (GC-EI-MS/MS). A QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe)-like procedure was applied; the extract was cleaned up on an acidic Extrelut-NT3 column connected on top of a silica cartridge and further purified with gel permeation chromatography (GPC). The SIM acquisition proved to yield better results than traditional MRM approach for octa-, nona-, and deca-brominated congeners. The validation study was carried out in inter-laboratory conditions. The average recoveries were in the range 66–118%, with relative standard deviations generally lower than or equal to 22%. Quality assurance and quality control practices were thoroughly described and highlighted. These long and tedious practices are fundamental to obtain reliable quantitative data during food monitoring programs and, therefore, to support daily intake assessments. Finally, the procedure was applied to the analysis of marine fish samples collected in local markets. Mackerel and mullet were the most contaminated species.     

Bio-inspired solutions for locomotion in the gastrointestinal tract: background and perspectives

This paper illustrates a bio-inspired approach to effective, smooth and safe navigation in the human body and, in particular, in the gastrointestinal tract. This idea originates from the medical need to develop more powerful tools for microendoscopy, which is one of the most challenging frontiers of modern medicine. Understanding motion and perception systems of lower animal forms, such as parasites, worms, insects and snakes, can help to design and fabricate bio-inspired robots able to navigate in tortuous, slippery and difficult-to-access cavities of the human body. A preliminary study of a biomimetic adhesion system for the human tissues is presented in this work and some technological implementations are illustrated and discussed. Finally, some issues concerning the goals of smart and reactive locomotion are considered and the most promising and relevant enabling technologies are discussed.     

Characterization of soil deformation due to blast-induced liquefaction by UAV-based photogrammetry and terrestrial laser scanning

ABSTRACT

Soil liquefaction due to an earthquake can lead to permanent soil deformation and reduction of load-bearing capacity that in turn could act on building stability. Since a quantitative evaluation of post-liquefaction settlements is often very difficult, field scale liquefaction tests, carried out under controlled conditions, such as blast tests, are used to perform a correct quantitative analysis of the liquefaction phenomena. Among the significant parameters related to a blast test, there are the geometric ones, i.e. the extension of the area affected by the blast-induced liquefaction and the corresponding vertical displacements. This article shows the results of a blast test carried out at a trial site located in Mirabello (Ferrara, Italy) from a remote-sensing perspective. Data provided by aerial Structure-from-Motion photogrammetry, supported by terrestrial laser scanning measurements, were used to evaluate the soil deformation that, in the specific case study, aided a geological/geotechnical interpretation of the blast test results. In general, the proposed method can be used to characterize areas affected by blast-induced liquefaction, including those cases where blasting is used as ground improvement technique aimed at mitigating the seismic hazard.     

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...