458 research outputs found
Square planar Au(III), Pt(II) and Cu(II) complexes with quinoline-substituted 2,2′:6′,2″-terpyridine ligands: From in vitro to in vivo biological properties
This work was supported by the Applied Molecular Biosciences Unit - UCIBIO which is financed by national funds from FCT (UIDP/04378/2020, UIDB/04378/2020 and fellowships SFRH/BPD/124612/2016 (C. Roma-Rodrigues), and PTDC/CVT-EPI/6685/2014 (L R. Raposo)).Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2′:6′,2″-terpyridine ligand: [Pt(4′-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4′-(2-quin)-terpy)Cl](PF6)2·CH3CN (2) and [Cu(4′-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 × lower than the IC50 displayed by cisplatin (15.4 μM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 >1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1–3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect.publishersversionpublishe
How do novel feed formulations affect growth performance, oxidative stress and immune response of atlantic salmon?
Trabajo presentado en la International Conference & Exposition Aquaculture Europe, celebrada en Funchal, Maderia (Portugal) del 04 al 07 de octubre de 2021.[Introduction]: The aquaculture industry continues to grow faster than any other sector of food production. The need to make aquaculture as sustainable and more environmentally conscious as possible is becoming clearer everyday (FAO, 2020). With this in mind, the replacement of fishmeal and fish oil in aquafeeds has been studied in Atlantic salmon (Salmo salar) (e.g., Bendiksen et al., 2011) with many products emerging as potential alternatives to conventional ones (e.g., Hodar et al., 2020). One of the main objectives of the EU project GAIN is to evaluate new ingredients that are already commercially available using different formulation concepts that consider all the fish nutritional needs. GAIN diets are based on circular economy principles and maximize resource efficiency, while contributing to zero waste in the agri-food value chain, being cost-effective feeds, and having good social acceptability. The present study aims to understand the actual effects of these novel feed formulations on growth performance, nutritional status, immunity and oxidative status.[Methods]: Quadruplicate groups of Atlantic salmon were fed ad libitum with three different diets. Two diets were developed to facilitate the eco-intensification of aquaculture through increased circularity and resource utilization (NOPAP - formula without processed animal protein - and PAP - formula with processed animal protein). The third diet was a commercial-like formulation that was used as a control. After a 96-day feeding trial, plasma samples were collected to evaluate humoral parameters (protease, anti-protease, bactericidal activity, and IgM). Liver and head kidney tissues (collected at day 45 and 96) were used for the simultaneous profiling by PCR array of a panel of 38 or 28 genes, respectively, as markers of growth performance, lipid and energy metabolism, and immune and antioxidant activities. Liver samples were also used to analyse lipid peroxidation. In addition, after 45 and 96 days, the lice count and fish welfare were also assessed by standard methods. The dorsal skin and foregut were collected at days 45 and 96 for mucosal mapping (mucous cell area, density, and barrier status).[Results]: Growth performance was adequate and comparable to commercial standards for the novel diets tested. Other parameters analysed, including those related to key performance indicators, intestinal and skin dorsal mucosal mapping, plasma innate immune defences, and lipid peroxidation in the liver did not significantly differ across diets. Regarding head kidney gene expression, at Day 45, 2 out of 28 genes in the array were differentially expressed (p<0.05). Gene expression of fish fed with novel feed formulations showed a pro-inflammatory profile evidenced by the up regulation of il-8, and a down regulation of il-10.At Day 96, the same genes continued to be differentially expressed, but gene clec1b (membrane protein) was also up-regulated. However, the rest of the analyses do not support this pro-inflammatory profile. A longer trial may bring light to some of the current results. In turn, the liver had a differential gene expression only at the second sampling point (Day96), where 4 out of 38 genes in the array were affected, including growth performance (igf2), lipid metabolism, elongases (elovl4), and energy metabolism (ucp2l and sirt1). These transcriptomic changes may be attributed to an initial response to
the experimental diets. Cross-analysis of gene expression by time points and dietary treatment (two-way ANOVA) yielded only 2 out of 38 genes that had significantly different expression across treatments. The differentially expressed genes were related to growth performance (igf2) and lipid metabolism (elovl4).[Conclusions]: The novel feed formulations of the GAIN project for Atlantic Salmon seem to be viable options for the near future. In any case, all results are related to the formulation itself and cannot be attributed to a specific ingredient alteration. More studies are necessary to understand the cost-benefit of these new formulations and their market acceptability to optimize sustainability within the current/predictable European regulatory framework.This project was financed by the European Union’s Horizon 2020 research and innovation programme under grant agreement N° 773330 (GAIN), with additional support from Nord University (Norway) and SPAROS Lda (Portugal)
Evaluation of growth performance, oxidative stress and immune response in gilthead sea bream fed with novel feed formulations
Trabajo presentado en Aquaculture Europe 2020, celebrado en modalidad virtual del 12 al 15 de abril de 2021.[Introduction]: As the aquaculture sector continues to expand while being more environmentally conscious, the development of sustainable aquafeeds is becoming increasingly important (FAO, 2020). Tolerance to the replacement of fishmeal and fish oil in feeds has been largely studied in gilthead seabream (Sparus aurata) (Gasco et al., 2018; Karapanagiotidis, Psofakis, Mente, Malandrakis, & Golomazou, 2019), and many products emerge now as potential alternatives to ingredients used in conventional formulations. A main goal of GAIN EU project is to evaluate emerging ingredients, already commercially available, using different formulation concepts that consider all fish nutritional requirements. GAIN diets are based on circularity principles, maximizing resource efficiency, while contributing towards zero waste in the agro-food value chain, feed cost-effectiveness, and having good social acceptance. The present study aims to understand the real impacts of these novel feed formulations on growth performance, nutritional condition, immunity, and oxidative status using biomarkers.[Methods]: Quadruplicate groups of gilthead seabream (Sparus aurata) were fed ad libitum with four different diets. Three of them have been designed to facilitate aquaculture eco-intensification through increased circularity and resource utilization: NOPAP - formula without terrestrial animal by-products processed animal protein; PAP - formula with terrestrial animal by-products processed animal protein; and MIX - a mixture of NOPAP and PAP. The fourth feed followed a standard commercial formulation and was used as a control diet. After a 77-day feeding trial, plasma samples were collected to evaluate humoral parameters (protease, anti-protease, bactericidal activity and IgM). Liver and head kidney tissues were collected for the simultaneous profiling of a panel of 42 (liver) or 29 (head kidney) genes, as markers of growth performance, lipid and energy metabolism, and immune and antioxidant activities by qPCR. Liver samples were also used to analyse oxidative biomarker (Lipid peroxidation and catalase).[Results]: Tested feed formulations did not affect growth performance or feed intake. However, fish fed PAP and MIX diets had a higher feed conversion ratio (FCR) and protein efficiency ratio than control and NOPAP groups. This impairment was accompanied by a decreased hepatic expression of igf-i and ghr1. NOPAP diet slightly increased innate immunity parameters, showing better results on bactericidal, IgM, and anti-protease activity, as well as a significant up-regulation of il-8 in head kidney. Fish fed with PAP diet displayed an up-regulation of pro-inflammatory genes, namely il-8 and other cytokines (il-1β, tnf-α), chemokines (ck8), and chemokine receptors (ccr3). The same pattern was found for the T-cell markers cd3x, cd4, and cd8a. The activity of the antioxidant enzyme catalase was significantly lower in fish fed with PAP and MIX diet, being a possible indication of decreased antioxidant defences. This is supported by the observed regulation of antioxidant genes (mn-sod/sod2, gpr-170, gpr-94, and gpr-75), although not statistically significant.[Discussion]: The similar performance of novel formulations and the control diet indicates that they can be considered as viable options for seabream feeds. Differences in FCR suggest that NOPAP can promote a better bioavailability and/or increased absorption of key nutrients than PAP and MIX diets. Indeed, this impairment was also evidenced by their hepatic expression pattern of markers of growth performance. In general, PAP exhibited an opposite response to the NOPAP group. NOPAP was closer to the control diet, and MIX showed intermediate values between PAP and NOPAP in almost all parameters. The markedly pro-inflammatory head kidney expression profile in PAP fish may be also indicative of an impaired response at the mucosal level. In any case, the low proportion of differentially expressed genes between the experimental diets and control (18 out of 71) constitutes an additional and indirect confirmation of their suitability.[Conclusions]: Novel feed formulations for gilthead seabream seem to be viable options for a near future. In any case, all results are related to the formulation itself and cannot be attributed to a specific ingredient alteration. More studies are necessary to understand the cost-benefit of these new formulations and their market acceptability to optimize sustainability within the current/predictable European regulatory framework.“This project was financed from the European Union’s Horizon 2020 research and innovation programme under grant agreement N° 773330 (GAIN), with additional support from Nord university (Norway) and Sparos SA (Portugal)”
Chemical composition of essential oils and anticholinesterasic activity of Eugenia sulcata Spring ex Mart.
The chemical composition of the essential oils from leaves and stems of Eugenia sulcata Spring ex Mart., obtained by hydrodistillation, was analyzed by GC-MS and quantified by CG-FID. In all, 37 components were identified and sesquiterpenes represented the largest fraction of both oils, in the leaves (58.2 %) and stems (85.3 %). The major constituent found in the essential oil from leaves and stems of E. sulcata was β-caryophyllene, corresponding to 24.6 % and 18.8 %, respectively. The substances α- cubebene (1.1 %), β-copaene (0.5 %), cis-muurola-3,5-diene (0.6 %), cis-muurola-4(14),5-diene (1.3 %), γ- himachalene (2.0 %), epizonarene (0.8 %), trans-calamenene (4.4 %) and trans-cadina-1,4-diene (3.4 %) were identified for the first time as chemical constituents of essential oil from leaves of E. sulcata. To our knowledge, this was the first phytochemical contribution to the essential oil from stems of E. sulcata. It was also performed the acetylcholinesterase inhibitory bioassay of the essential oil from leaves of E. sulcata, which was considered active and exhibited an IC50 value of 4.66 ± 0.48 μg.mL-1.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Comparative study and anticholinesterasic evaluation of essential oils from leaves, stems and flowers of myrciaria floribunda (H.West ex Willd.) O. Berg
Myrciaria floribunda (H.West ex Willd.) O.Berg, Myrtaceae, popularly known as “camboim amarelo”, was collected in Restinga de Jurubatiba (RJ, Brazil). Leaves, stems and flowers were individually submitted to hydrodistillation, affording the respective essential oils. Monoterpenes were the main group of essential oils from leaves (53.9 %) and flowers (55.4 %). Sesquiterpenes were more representative in stems (72.2 %). 1,8-cineole was the major constituent in the essential oil from leaves (38.4 %) and flowers (22.8 %). The major constituent from stems was (2E,6E)-farnesyl acetate (19.9 %). To our knowledge, these are the first contributions for essential oils from stems and flowers of M. floribunda. It was also performed the acetylcholinesterase inhibitory bioassay of the essential oil from stems, flowers and leaves of M.
floribunda. Flowers and leaves oils had an IC50 of 1583 and 681 μg/mL, respectively, being both low to mild values.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Chemical and biological study of essential oils from <i>Eugenia pruniformis</i> Cambess., an endemic species from Brazilian Atlantic Forest
Eugenia pruniformis Cambess. is an endemic species from Brazilian Atlantic Forest. Essential oils from leaves and fruits from this species were obtained by hydrodistillation and analyzed by GCMS/CG-FID. In all, 25 compounds were identified, with predominance of sesquiterpene hydrocarbons in both plant parts. The major compounds were β-caryophyllene, bicyclogermacrene, germacrene D, δ- cadinene and α-copaene. Antioxidant activity was performed for essential oil from leaves using ORAC method, showing value of 0.30 ± 0.06 mmol TE/g. Anticholinesterasic evaluation was also performed for this oil, indicating that it inhibited acetylcholinesterase, showing an IC50 of 1798 μg/mL. These results indicate that this essential oil may be considered as a potential source of substances for Alzheimer’s disease Treatment. To our knowledge, these are the first contributions to biological and phytochemical characterization of E. pruniformis, an almost unexplored species from Brazilian Atlantic Forest.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Cork : properties, capabilities and applications
Cork is a natural, renewable, sustainable raw material that has been used for many centuries. As a result of this very long term interest, the scientific literature on cork is extensive. The present review focuses on the chemical composition, physical and mechanical properties of cork and on its products and sub-products. The substantial efforts to fully characterise cork, as well as new developments and evolving research, are reviewed, beginning with its histology, growth and morphology (at macro- and microscales). The chemical structure is analysed in detail, covering both the materials that form the wall structure and the low molecular weight, extractable components. The unique properties of cork are discussed and correlated with current knowledge on morphology and chemical structure. Finally, the important industrial applications of cork are reviewed, in the context of research to provide cork with novel, high added-value applications
Pulmonary artery enlargement in schistosomiasis associated pulmonary arterial hypertension
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