Platinum-Nucleos(t)ide Compounds as Possible Antimetabolites for Antitumor/Antiviral Therapy: Properties and Perspectives

Nucleoside analogues (NAs) are a family of compounds which include a variety of purine and pyrimidine derivatives, widely used as anticancer and antiviral agents. For their ability to compete with physiological nucleosides, NAs act as antimetabolites exerting their activity by interfering with the synthesis of nucleic acids. Much progress in the comprehension of their molecular mechanisms has been made, including providing new strategies for potentiating anticancer/antiviral activity. Among these strategies, new platinum-NAs showing a good potential to improve the therapeutic indices of NAs have been synthesized and studied. This short review aims to describe the properties and future perspectives of platinum-NAs, proposing these complexes as a new class of antimetabolites

A NMR-Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (phen = 1,10-Phenanthroline) Compound on Neuroblastoma Cancer Cells

none7NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ1-C2H4OMe)(DMSO)(phen)]+ (phen 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH-SY5Y). In this study, the mechanism of action of Pt-EtOMeSOphen on SH-SY5Y cells was investigated using 1H NMR-based metabolomics and compared with cisplatin. ­e observed time response of SH-SY5Y cells under treatment revealed a faster action of PtEtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR-based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression.De Castro, Federica; Stefano, Erika; De Luca, Erik; Muscella, Antonella; Marsigliante, Santo; Benedetti, Michele; Fanizzi, Francesco PaoloDe Castro, Federica; Stefano, Erika; De Luca, Erik; Muscella, Antonella; Marsigliante, Santo; Benedetti, Michele; Fanizzi, Francesco Paol

First evidence for N7-Platinated Guanosine derivatives cell uptake mediated by plasma membrane transport processes

Nucleos(t)ide analogues (NA) belong to a family of compounds widely used in anticancer/antiviral treatments. They generally exhibit a cell toxicity limited by cellular uptake levels and the resulting nucleos(t)ides metabolism modifications, interfering with the cell machinery for nucleic acids synthesis. We previously synthesized purine nucleos(t)ide analogues N7-coordinated to a platinum centre with unaltered sugar moieties of the type: [Pt(dien)(N7-dGuo)]2+ (1; dien = diethylenetriamine; dGuo = 2′-deoxy-guanosine), [Pt(dien)(N7-dGMP)] (2; dGMP = 5′-(2′-deoxy)-guanosine monophosphate), and [Pt(dien)(N7-dGTP)]2− (3; dGTP = 5′-(2′-deoxy)-guanosine triphosphate), where the indicated electric charge is calculated at physiological pH (7.4). In this work, we specifically investigated the uptake of these complexes (1–3) at the plasma membrane level. Specific experiments on HeLa cervical cancer cells indicated a relevant cellular uptake of the model platinated deoxynucleos(t)ide 1 and 3 while complex 2 appeared unable to cross the cell plasma membrane. Obtained data buttress an uptake mechanism involving Na+-dependent concentrative transporters localized at the plasma membrane level. Consistently, 1 and 3 showed higher cytotoxicity with respect to complex 2 also suggesting selective possible applications as antiviral/antitumor drugs among the used model compounds

The Italian Agreement between the Government and the Regional Authorities: National Guidelines for AAI and Institutional Context

Animal-assisted interventions (AAI) have developed considerably in the last half century, prompting various private and public realities dealing with AAI worldwide to work on and establish standards and best practice. However, AAI are still far from being regulated harmoniously. In this context, Italy offers a unique example at world level: here the spread of AAI has set in motion an ethical and legal reflection that led to the creation of the Italian National Reference Centre for AAI (NRC AAI) by ministerial decree in 2009 and the approval of National Guidelines for AAI in 2015. The Italian legislation on AAI is based on the One Health approach, which has been part of Italian health culture and institutions since the Renaissance. The synergy between human and veterinary medicine is the core of this theme: in other words, One Health represents a multidisciplinary approach aimed at best protecting the health and well-being of all those who share our planet. In Italy, human and veterinary medicine have both been placed under the umbrella of the Ministry of Health since its establishment in 1958. The same idea of collaboration is at the heart of the Italian legislative approach to the AAI field, given the inherent multidisciplinarity of these interventions. This applies to all indications provided by the National Guidelines, for example the distinction between the various types of interventions, the animal species involved, the roles within the multidisciplinary team, and the training programs for each professional figure. In addition, the National Guidelines are intended to be amendable according to the needs arising over time from daily practice: in fact, the constant contact and dialogue between institutions and AAI professionals is another pillar of the Italian approach

Wireframe DNA Origami for the Cellular Delivery of Platinum(II)-Based Drugs

The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes

Comparison between balloon angioplasty and additional coronary stent implantation for the treatment of drug-eluting stent restenosis: 18-month clinical outcomes

OBJECTIVE: To evaluate the long-term outcomes after different modalities of treatment of drug-eluting stent (DES) in-stent restenosis (ISR) in a 'real world' setting. METHODS: Actually, few and conflicting data are available about the management of in-stent restenosis (ISR) after DES implantation. In our 'real world' registry 1082 consecutive patients who received a DES implantation were included. At 9-month angiographic follow-up, 93 patients presented a DES ISR that was treated with 'homo-DES' (HMD) (N = 27), 'hetero-DES' (HTD) (N = 19) and conventional balloon angioplasty (POBA) (N = 47). We evaluated the clinical outcomes in terms of major adverse cardiac event (MACE) (death, myocardial infarction and target vessel revascularization) at 18 months. RESULTS: There was no difference for clinical and angiographic characteristics between the three groups, except for the presence of silent ischaemia as clinical presentation (7.7 HMD vs. 2.2% POBA; P = 0.0001). No late stent thrombosis was found. At 18-month clinical follow-up patients treated with HMD, HTD and POBA presented a rate of MACE of 10.2, 0 and 8.7%, respectively (P = NS). Kaplan-Meier survival probability showed that HTD and POBA treatment tended to have more favourable outcomes at 18 months than the HMD treatment. CONCLUSION: In our registry, POBA seems to be as effective as other DES implantations in cases of DES ISR, especially in cases of focal type (Mehran classification IA, IC), in terms of long-term outcomes

Storage of minimally processed cabbage in differents packaging systems

Stability of fresh-cut cabbage packed in low density polyethylene under active modified atmosphere and in expanded polyestyrene trays wrapped with PVC was evaluated. The fresh-cut product was stored for 16 days in a cold room at 5 ± 1 °C and 95 ± 5% RH and in a refrigerated display case similar to those found in grocery stores. The following variables were analyzed: content of oxygen and carbon dioxide inside the package headspace; browning, luminosity, polyphenoloxidase and peroxidase activities, pH, titratable acidity; soluble solids, fresh mass loss, and ascorbic acid content. The stability of fresh-cut cabbage was higher at the temperature of 5 °C compared to those stored in the refrigerated displays. The active modified atmosphere was not effective in extending the shelf life of fresh-cut cabbage compared to other treatments. LDPE packaging was more adequate for fresh-cut cabbage storage. However, PVC wrapping also presented satisfactory effects.Avaliou-se a estabilidade de repolho minimamente processado acondicionado em embalagens de polietileno de baixa densidade com atmosfera modificada ativa e passiva, e em bandejas de poliestireno expandido revestidas com filme de policloreto de vinila. O produto foi armazenado por 16 dias em câmara frigorífica na temperatura de 5 ± 1 °C e 95 ± 5 % de umidade relativa, e em um balcão refrigerado similar aos utilizados em lojas de conveniência, com o intuito de representar os locais de comercialização no varejo, com temperatura média de 2,7 ± 3,3 °C. Analisou-se a concentração de oxigênio e dióxido de carbono no interior das embalagens, e no repolho minimamente processado o incremento no escurecimento, luminosidade, atividade da polifenoloxidase e peroxidase, pH, acidez titulável, sólidos solúveis, perda de massa fresca e teor de ácido ascórbico. A estabilidade do repolho minimamente processado mostrou-se superior na temperatura de 5 °C quando comparada ao armazenamento no balcão refrigerado. A atmosfera modificada ativa não foi efetiva no aumento da vida útil do repolho minimamente processado quando comparada aos outros tratamentos. A embalagem de PEBD foi a mais adequada ao acondicionamento do repolho minimamente processado. No entanto, a embalagem de PVC também apresentou resultados satisfatórios.310315Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Modeling macroalgal forest distribution at Mediterranean scale : present status, drivers of changes and insights for conservation and management

Macroalgal forests are one of the most productive and valuable marine ecosystems, but yet strongly exposed to fragmentation and loss. Detailed large-scale information on their distribution is largely lacking, hindering conservation initiatives. In this study, a systematic effort to combine spatial data on Cystoseira C. Agardh canopies (Fucales, Phaeophyta) was carried out to develop a Habitat Suitability Model (HSM) at Mediterranean scale, providing critical tools to improve site prioritization for their management, restoration and protection. A georeferenced database on the occurrence of 20 Cystoseira species was produced collecting all the available information from published and grey literature, web data portals and co-authors personal data. Data were associated to 55 predictor variable layers in the (ASCII) raster format and were used in order to develop the HSM by means of a Random Forest, a very effective Machine Learning technique. Knowledge about the distribution of Cystoseira canopies was available for about the 14% of the Mediterranean coastline. Absence data were available only for the 2% of the basin. Despite these gaps, our HSM showed high accuracy levels in reproducing Cystoseira distribution so that the first continuous maps of the habitat across the entire basin was produced. Misclassification errors mainly occurred in the eastern and southern part of the basin, where large gaps of knowledge emerged. The most relevant drivers were the geomorphological ones, followed by anthropogenic variables proxies of pollution and urbanization. Our model shows the importance of data sharing to combine a large number of spatial and environmental data, allowing to individuate areas with high probability of Cystoseira occurrence as suitable for its presence. This approach encourages the use of this modeling tool for the prediction of Cystoseira distribution and for supporting and planning conservation and management initiatives. The step forward is to refine the spatial information of presence-absence data about Cystoseira canopies and of environmental predictors in order to address species-specific assessments.peer-reviewe

Terahertz confocal microscopy with a quantum cascade laser source

We report on the implementation of a confocal microscopy system based on a 2.9 THz quantum cascade laser source. Lateral and axial resolutions better than 70 \u3bcm and 400 \u3bcm, respectively, are achieved, with a large contrast enhancement compared to the non-confocal arrangement. The capability of resolving overlapping objects lying on different longitudinal planes is also clearly demonstrated