Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: synthesis and characterization

Bisphosphonates (BPs) are an important class of drugs used in the treatment of abnormal calcium metabolism diseases. The first syntheses of bisphosphonates derived from indazole, substituted at the N-1, N-2 and C-3 positions are reported. The 1-hydroxy-1,1-bisphosphonates were synthesized from the corresponding carboxylic acid or acyl chloride compounds, by two different methods. These BPs have a side chain with different lengths ((CH2)n, n = 0-5) between the indazole ring and the bisphosphonate group

The interaction of La3+ complexes of DOTA/DTPA-glycoconjugates with the RCA120 lectin : a saturation transfer difference (STD) NMR spectroscopic study

The study of ligand-receptor interactions using high resolution NMR techniques, namely the Saturation Transfer Difference (STD), is presented for the recognition process between La(III) complexes of DOTA mono(amide) and DTPA bis(amide) glycoconjugates and the galactose specific lectin Ricinus Communis agglutinin (RCA120). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one or two terminal sugar (galactosyl or lactosyl) moieties, has been designed for in vivo binding to ASGPR (the asialoglycoprotein receptor), which is specifically expressed at the surface of liver hepatocytes, with the aim of leading to a new possible diagnosis of liver pathologies. The in vitro affinity constants of the divalent La(III)- glycoconjugate complexes to RCA120, used as a simple, water soluble receptor model, were higher than those of the monovalent analogues. The combination of the experimental data obtained from the STD NMR experiments with molecular modelling protocols (Autodock 4.1) allowed us to predict the binding mode of mono and divalent forms of these CAs to the galactose 1 binding sites of RCA120. The atomic details of the molecular interactions allowed corroborating and supporting the interaction of both the sugar moieties and the linkers with the surface of the protein and thus, their contribution to the observed interaction stabilities.Fundação para a Ciência e a Tecnologia (FCT

Alendronic acid as ionic liquid: New perspective on osteosarcoma

This work was supported by the Associate Laboratory for Green Chemistry LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020). The authors also thank Fundacao para a Ciencia e Tecnologia for the projects PTDC/QUI-QOR/32406/2017, PEst-C/LA0006/2013 and RECI/BBBBQB/0230/2012), as well as one contract under Investigador FCT (L. C. Branco).Herein the quantitative synthesis of eight new mono-and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.publishersversionpublishe

Exploring the potential of web based information of business popularity for supporting sustainable traffic management

This paper explores the potential of using crowdsourcing tools, namely Google "Popular times" (GPT) as an alternative source of information to predict traffic-related impacts. Using linear regression models, we examined the relationships between GPT and traffic volumes, travel times, pollutant emissions and noise of different areas in different periods. Different data sets were collected: i) crowdsourcing information from Google Maps; ii) traffic dynamics with the use of a probe car equipped with a Global Navigation Satellite System data logger; and iii) traffic volumes. The emissions estimation was based on the Vehicle Specific Power methodology, while noise estimations were conducted with the use of “The Common Noise Assessment Methods in Europe” (CNOSSOS-EU) model. This study shows encouraging results, as it was possible to establish clear relationships between GPT and traffic and environmental performance.in publicatio

Avaliação Nutricional de um Suplemento Alimentar

A escolha da nutrição mais adequada tem sido um tema estudado com grande interesse ao longo da história da humanidade tendo em conta a manutenção da Saúde, mas igualmente com outras finalidades como o atraso do envelhecimento ou outros benefícios. O desafio colocado pela ingestão de frutos, vegetais, cereais, azeite e vinho aplicado pela intitulada Dieta Mediterrânica torna possível o entendimento de países com diversas etnias, culturas, economia e religiões, todos eles à volta do mar Mediterrâneo. Por outro lado, o contínuo aparecimento de patologias como os acidentes vasculares cerebrais, o cancro e a aterosclerose podem ser de algum modo minimizadas pela ingestão de alguns compostos bioativos presentes nos alimentos, os chamados nutracêuticos e alimentos funcionais. O objetivo deste trabalho foi fazer uma revisão dos estudos publicados sobre os efeitos do licopeno na saúde humana, uma abordagem da respetiva química, fontes, biodisponibilidade e do potencial possível papel e mecanismos desempenhado na prevenção de determinadas doenças crónicas e no cancro. O licopeno é um dos antioxidantes mais potentes conhecidos, constituindo porventura o carotenóide mais importante presente na dieta, maioritariamente fornecido através do tomate e derivados. Atendendo a que o organismo humano não consegue sintetizar este composto de novo, este tem obrigatoriamente que ser fornecido pela dieta. No entanto, a sua biodisponibilidade pode ser afetada por inúmeros fatores tais como a forma de digestão da matriz alimentar, a temperatura de confecção, pela presença de outras gorduras no alimento, dosagem e outros compostos solúveis, incluindo os outros carotenóides. Esses fatores causam a libertação de licopeno a partir da matriz de alimentos e alteram assim a sua biodisponibilidade.info:eu-repo/semantics/publishedVersio

The economic impact of a new type of ripening chamber in traditional cheese manufacturing

ALT20-03-0145-FEDER-023356 UIDP/04035/2020 UIDB/05064/2020A new prototype of a ripening chamber was proposed in the CFD4CHEESE project aiming to evaluate the application of computational fluid dynamics in the optimization of traditional cheeses ripening conditions. With the purpose of evaluating the possible impact on the energy cost of cheese ripening in three Portuguese regions (Setubal, Evora, and Beja), we demonstrated the potential economic benefits of the prototype. The proposed automation process would imply higher productive efficiency, reducing the consumption of water and electricity. The simple consideration of the reduction of electricity costs is enough to recover the investment needed to have the new ripening chambers, meaning that the investment is economically viable. In addition to the economic impact in firms, which are mostly small and medium firms, our results also contribute to an increase on the sustainable use of natural resources.publishersversionpublishe

Information Management for Smart and Sustainable Mobility

The main objective of this work is to present a modular platform to manage traffic information for smart mobility. The management and collection of dynamic data is a challenging process especially in the context of low penetration of floating car data (FCD) and limited availability of traffic monitoring stations. In this work, three different road segments of a European medium-sized city were selected to collect vehicle dynamic data over multiple scenarios of traffic demand. Simultaneously, traffic volumes were recorded in real time. The main objective of this pilot experiment was to assess how it would be possible to read and predict traffic congestion and emissions levels with limited information and how data from multiple sources should be managed in order to correlate and deal with this information in real time. It was possible to correlate simultaneously multiple data set such as congestion values, specific vehicle power (VSP) mode distribution, Google traffic data and emission. Preliminary findings suggest that in urban arterials travel time and congestion levels can be reliable indicators for estimating emissions in real time. In sections of rural arterials, the estimation of real-time traffic performance is more complex. Key issues towards the implementation of a prototyping platform in an urban context are also discusse

Fatty acids profile of Serra da Estrela PDO cheeses and respective atherogenic and thrombogenic indices

Purpose: This study aims to determine the physicochemical and fatty acids composition of Serra da Estrela cheese (SEC), as well as health-related lipid indices, like the atherogenic and thrombogenic indices, and to evaluate the influence of producer, geographical origin and production date. Design/methodology/approach: All 24 SEC produced between November 2017 and March 2018 were collected at selected certified producers and analyzed by NIR spectrophotometer and by GC. Data were statistically evaluated by chemometric tools. Findings: In all evaluated SEC, 23 fatty acids were quantified. Cheese origin influenced nutritional and health-related lipid indices). The cheeses were characterized by a relative high abundance of saturated fatty acids (67-76%), followed by a medium content of monounsaturated fatty acids (17-25%) and by low level of polyunsaturated fatty acids (5-7%). A putative positive association between cheese consumption and healthy lipid indices could be reached. Practical implications The contents of some medium and long chain fatty acids as well as of nutritional and health indices were influenced by cheese producer, geographical origin and production date pointing out the need for standardizing production procedures. Social implications The SEC plays a key role in the local economy, being an endogenous product with unique sensory characteristics and nutritional potential, for which the knowledge of the lipids profile and health indices is of utmost relevance. Originality/value SEC is an iconic Portuguese cheese with Protected Designation of Origin. Based on the results, like health-related lipid indices, evaluated for the first time, a positive association between cheese consumption and healthy lipid indices could be envisaged.This work was financially supported by Associate Laboratory LSRE-LCM - UID/EQU/50020/2019, strategic funding UID/BIO/04469/2019-CEB and BioTecNorte operation (NORTE-01-0145-FEDER000004), and strategic project PEst-OE/AGR/UI0690/2014–CIMO funded by national funds through FCT/MCTES (PIDDAC). The authors would also like to acknowledge the funding provided by the approved Project, with reference 02/SAICT/2016/23290, entitled Characterization and Valorization of QSE PDO and its ability for health promotion (QCLASSE), financed by FCT.info:eu-repo/semantics/publishedVersio

Molecular cloning and characterization of a highly selective chemokine-binding protein from the tick Rhipicephalus sanguineus.

Abstract Ticks are blood-feeding parasites that secrete a number of immuno-modulatory factors to evade the host immune response. Saliva isolated from different species of ticks has recently been shown to contain chemokine neutralizing activity. To characterize this activity, we constructed a cDNA library from the salivary glands of the common brown dog tick, Rhipicephalus sanguineus. Pools of cDNA clones from the library were transfected into HEK293 cells, and the conditioned media from the transfected cells were tested for chemokine binding activity by chemical cross-linking to radiolabeled CCL3 followed by SDS-PAGE. By de-convolution of a single positive pool of 270 clones, we identified a full-length cDNA encoding a protein of 114 amino acids, which after signal peptide cleavage was predicted to yield a mature protein of 94 amino acids that we called Evasin-1. Recombinant Evasin-1 was produced in HEK293 cells and in insect cells. Using surface plasmon resonance we were able to show that Evasin-1 was exquisitely selective for 3 CC chemokines, CCL3 and CCL4 and the closely related chemokine CCL18, with KD values of 0.16, 0.81, and 3.21 nm, respectively. The affinities for CCL3 and CCL4 were confirmed in competition receptor binding assays. Analysis by size exclusion chromatography demonstrated that Evasin-1 was monomeric and formed a 1:1 complex with CCL3. Thus, unlike the other chemokine-binding proteins identified to date from viruses and from the parasitic worm Schistosoma mansoni, Evasin-1 is highly specific for a subgroup of CC chemokines, which may reflect a specific role for these chemokines in host defense against parasites