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Diiron vinyliminium complexes constitute a large family of organometallics displaying a promising anticancer potential. The complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(R3)C(R4)CN(R1)(R2)}]CF3SO3 (2a-c, 4a-d) were synthesized, assessed for their behavior in aqueous solutions (D2O solubility, Log Pow, stability in D2O/Me2SO-d6 mixture at 37°C over 48 h) and investigated for their antiproliferative activity against A2780 and A2780cisR ovarian cancer cell lines and the nontumoral one Balb/3T3 clone A31. Cytotoxicity data collected for 50 vinyliminium complexes were correlated with the structural properties (i.e. the different R1-R4 substituents) using the partial least squares methodology. A clear positive correlation emerged between the octanol-water partition coefficient and the relative antiproliferative activity on ovarian cancer cell lines, both of which appear as uncorrelated to the cancer cell selectivity. However, the different effects played by the R1-R4 substituents allow tracing guidelines for the development of novel, more effective compounds. Based on these results, three additional complexes (4p-r) were designed, synthesized and biologically investigated, revealing their ability to hamper thioredoxin reductase enzyme and to induce cancer cell production of reactive oxygen species.
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Neoplasias Ováricas , Humanos , Femenino , Línea Celular Tumoral , Ligandos , Cristalografía por Rayos X , Neoplasias Ováricas/tratamiento farmacológico , Especies Reactivas de OxígenoRESUMEN
Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.
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Poliésteres , Andamios del Tejido , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea , Hidroxibutiratos , Ratones , Poliésteres/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture.
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Hidrogeles , Neoplasias Ováricas , Carcinoma Epitelial de Ovario , Matriz Extracelular/química , Humanos , Hidrogeles/química , Polímeros/química , Microambiente TumoralRESUMEN
Amphiphilic copolymers are appealing materials because of their interesting architecture and tunable properties. In view of their application in the biomedical field, the preparation of these materials should avoid the use of toxic compounds as catalysts. Therefore, enzymatic catalysis is a suitable alternative to common synthetic routes. Pentablock copolymers (CUC) were synthesized with high yields by ring-opening polymerization of ε-caprolactone (ε-CL) initiated by Pluronic (EPE) and catalyzed by Candida antarctica lipase B enzyme. The variables to study the structure-property relationship were EPEs' molecular weight and molar ratios between ε-CL monomer and EPE macro-initiator (M/In). The obtained copolymers were chemically characterized, the molecular weight determined, and morphologies evaluated. The results suggest an interaction between the reaction time and M/In variables. There was a correlation between the differential scanning calorimetry data with those of X-ray diffraction (WAXD). The length of the central block of CUC copolymers may have an important role in the crystal formation. WAXD analyses indicated that a micro-phase separation takes place in all the prepared copolymers. Preliminary cytotoxicity experiments on the extracts of the polymer confirmed that these materials are nontoxic.
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Caproatos/química , Lactonas/química , Poloxámero/química , Polímeros/química , Rastreo Diferencial de Calorimetría/métodos , Catálisis , Peso Molecular , PolimerizacionRESUMEN
In this study, we report the realization of drug-loaded smart magnetic nanocarriers constituted by superparamagnetic iron oxide nanoparticles encapsulated in a dual pH- and temperature-responsive poly (N-vinylcaprolactam-co-acrylic acid) copolymer to achieve highly controlled drug release and localized magnetic hyperthermia. The magnetic core was constituted by flower-like magnetite nanoparticles with a size of 16.4 nm prepared by the polyol approach, with good saturation magnetization and a high specific absorption rate. The core was encapsulated in poly (N-vinylcaprolactam-co-acrylic acid) obtaining magnetic nanocarriers that revealed reversible hydration/dehydration transition at the acidic condition and/or at temperatures above physiological body temperature, which can be triggered by magnetic hyperthermia. The efficacy of the system was proved by loading doxorubicin with very high encapsulation efficiency (>96.0%) at neutral pH. The double pH- and temperature-responsive nature of the magnetic nanocarriers facilitated a burst, almost complete release of the drug at acidic pH under hyperthermia conditions, while a negligible amount of doxorubicin was released at physiological body temperature at neutral pH, confirming that in addition to pH variation, drug release can be improved by hyperthermia treatment. These results suggest this multi-stimuli-sensitive nanoplatform is a promising candidate for remote-controlled drug release in combination with magnetic hyperthermia for cancer treatment.
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Recurrent microbial infections are a major cause of surgical failure and morbidity. Wound healing strategies based on hydrogels have been proposed to provide at once a barrier against pathogen microbial colonization, as well as a favorable environment for tissue repair. Nevertheless, most biocompatible hydrogel materials are more bacteriostatic than antimicrobial materials, and lack specific action against pathogens. Silver-loaded polymeric nanocomposites have efficient and selective activity against pathogenic organisms exploitable for wound healing. However, the loading of metallic nanostructures into hydrogels represents a major challenge due to the low stability of metal colloids in aqueous environments. In this context, the aim of the present study was the development of highly stable silver nanoparticles (AgNPs) as novel potential antimicrobial agents for hyaluronic acids hydrogels. Two candidate stabilizing agents obtained from natural and renewable sources, namely cellulose nanocrystals and ulvan polysaccharide, were exploited to ensure high stability of the silver colloid. Both stabilizing agents possess inherent bioactivity and biocompatibility, as well as the ability to stabilize metal nanostructures thanks to their supramolecular structures. Silver nitrate reduction through sodium borohydride in presence of the selected stabilizing agents was adopted as a model strategy to achieve AgNPs with narrow size distribution. Optimized AgNPs stabilized with the two investigated polysaccharides demonstrated high stability in phosphate buffer saline solution and strong antimicrobial activity. Loading of the developed AgNPs into photocrosslinked methacrylated hyaluronic acid hydrogels was also investigated for the first time as an effective strategy to develop novel antimicrobial wound dressing materials.
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Antiinfecciosos/química , Antiinfecciosos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Nanopartículas del Metal/química , Plata/química , Cicatrización de Heridas/efectos de los fármacos , Vendajes , Celulosa/química , Nanocompuestos/química , Polisacáridos/químicaRESUMEN
A series of bioactive molecules were synthesized from the condensation of aspirin or chlorambucil with terminal alkynes bearing alcohol or amine substituents. Insertion of the resulting alkynes into the iron-carbyne bond of readily accessible diiron bis(cyclopentadienyl) µ-aminocarbyne complexes, [1a,b]CF3SO3, afforded novel diiron complexes with a bridging vinyliminium ligand, [2-10]CF3SO3, functionalized with a bioactive moiety. All compounds were characterized by elemental analysis and IR and multinuclear NMR spectroscopy and in three cases by single-crystal X-ray diffraction. Moreover, the D2O solubility, stability in D2O and cell culture media, and octanol-water partition coefficients of diiron complexes were determined spectroscopically. The cytotoxicity of the complexes was assessed in the tumorigenic A2780 and A2780cisR and the nontumorigenic HEK 293T cell lines. Some complexes exhibit high potency and the ability to overcome resistance in A2780cisR cells (aspirin complexes) or high selectivity relative to HEK 293T cells (chlorambucil complexes). Further studies indicate that the complexes significantly trigger intracellular ROS production, irrespective of the nature of the bioactive fragment. DNA alkylation and protein binding studies were also undertaken.
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The present study aimed to assess the toxicity of seven UV-filters: zinc oxide nanoparticles (nZnO, particle size <100 nm), titanium dioxide nanoparticles (nTiO2, primary particle size 21 nm), 2-ethylhexyl-4-methoxycinnamate (EHMC), 4-methylbenzylidene camphor (4-MBC), avobenzone (AVO), octocrylene (OCTO) and benzophenone-3 (BP-3) on three species: Aliivibrio fischeri (inhibition of bioluminescence), Phaeodactylum tricornutum (growth inhibition) and Ficopomatus enigmaticus (larval development success). Results showed nTiO2 to be the most toxic for P. tricornutum (EC50 0.043 mg L-1), while no effect was observed in A. fischeri and F. enigmaticus. EHMC was the most toxic to A. fischeri (EC50 0.868 mg L-1 (15 min) and 1.06 mg L-1 (30 min)) and the second most toxic to P. tricornutum. For F. enigmaticus, the lowest percentages of correct development resulted from 4-MBC exposure, with EC50 of 0.836 mg L-1. Overall, AVO induced low toxicity to every assessed species and OCTO was the least toxic for F. enigmaticus larvae. Considering the results obtained for F. enigmaticus, further larval development assays were performed with nZnO and EHMC under different light (light vs darkness) and temperature (20 and 25 °C) conditions, showing higher percentages of correct development at 25 °C, independently on light/darkness conditions. Under different temperature and photoperiod conditions, nZnO was more toxic than EHMC. Overall, nZnO and EHMC were among the most toxic UV filters tested and, when testing the effects of these UV-filters with temperature the results highlight that the impacts are liable to be lessened at higher temperatures (25 °C compared with 20 °C), in the case of this estuarine polychaete species. Nevertheless, further experiments are necessary to describe the effects of these two UV-filters at different organization levels, to study the toxicity of eventual degradation by-products and to provide more information on the combination of different stressors.
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Poliquetos , Contaminantes Químicos del Agua , Animales , Bioensayo , Ecotoxicología , Protectores Solares/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(R')C(Râ³)CN(R)(Y)}]CF3SO3 (2-7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69-95% yields from the reactions of diiron µ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R' = Râ³ = Me) and 3a (R = CH2CH=CH2, Y = R' = Me, Râ³ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV-Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol-water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2-7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R' = Râ³ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).
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The co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert a weaker selection for resistance than conventional antibiotics. In a previous study, we demonstrated that a low-molecular-weight quaternized chitosan derivative, named QAL, displays antibiofilm activity against the major pathogen Pseudomonas aeruginosa at subinhibitory concentrations. The aim of this study was to investigate whether QAL was able to inhibit the production of relevant virulence factors of P. aeruginosa. When tested in vitro at subinhibiting concentrations (0.31-0.62 mg/mL), QAL markedly reduced the production of pyocyanin, pyoverdin, proteases, and LasA, as well as inhibited the swarming motility of three out of four P. aeruginosa strains tested. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analyses demonstrated that expression of lasI and rhlI, two QS-related genes, was highly downregulated in a representative P. aeruginosa strain. Confocal scanning laser microscopy analysis suggested that FITC-labelled QAL accumulates intracellularly following incubation with P. aeruginosa. In contrast, the reduced production of virulence factors was not evidenced when QAL was used as the main polymeric component of polyelectrolyte-based nanoparticles. Additionally, combination of sub-MIC concentrations of QAL and tobramycin significantly reduced biofilm formation of P. aeruginosa, likely due to a synergistic activity towards planktonic bacteria. Overall, the results obtained demonstrated an antivirulence activity of QAL, possibly due to polymer intracellular localization and QS-inhibition, and its ability to inhibit P. aeruginosa growth synergizing with tobramycin.
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The generation of engineered models of the osteochondral complex to study its pathologies and develop possible treatments is hindered by the distinctly different properties of articular cartilage and subchondral bone, with the latter characterized by vascularization. In vitro models of the osteochondral complex have been mainly engineered as biphasic constructs containing just cartilage and bone cells, a condition very dissimilar from the in vivo environment. The different cellular components of the osteochondral complex are governed by interacting biochemical signaling; hence, to study the crosstalk among chondrocytes, osteoblasts, and endothelial cells, we have developed a novel triphasic model of the osteochondral tissue interface. Wet-spun poly(ε-caprolactone) (PCL) and PCL/hydroxyapatite (HA) scaffolds in combination with a methacrylated gelatin (gelMA) hydrogel were used as the polymeric backbone of the constructs. The scaffold components were engineered with human bone marrow derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs), and differentiated using a dual chamber microphysiological system (MPS) bioreactor that allows the simultaneous, separate flow of media of different compositions for induced differentiation of each compartment towards a cartilaginous or osseous lineage. Within the engineered Microphysiological Vascularized Osteochondral System, hMSCs showed spatially distinct chondrogenic and osteogenic markers in terms of histology and gene expression. HUVECs formed a stable capillary-like network in the engineered bone compartment and enhanced both chondrogenic and osteogenic differentiation of hMSCs, resulting in the generation of an in vitro system that mimics a vascularized osteochondral interface tissue.
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Células Madre Mesenquimatosas , Osteogénesis , Condrogénesis , Células Endoteliales , Humanos , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
In the marine environment, organisms are exposed to a high and increasing number of different contaminants that can interact among them. In addition, abiotic factors can change the dynamics between contaminants and organisms, thus increasing or even decreasing the toxic effect of a particular compound. In this study, the effects of caffeine (CAF) and functionalized multi-walled carbon nanotubes (f-MWCNTs) induced in the clam Ruditapes philippinarum were evaluated, acting alone and in combination (MIX), under two temperature levels (18 and 21 °C). To assess the impact of such compounds, their interaction and the possible influence of temperature, biochemical and histopathological markers were investigated. The effects of f-MWCNTs and caffeine appear to be clearly negative at the control temperature, with lower protein content in contaminated clams and a significant decrease in their metabolism when both pollutants were acting in combination. Also, at control temperature, clams exposed to pollutants showed increased antioxidant capacity, especially when caffeine was acting alone, although cellular damages were still observed at CAF and f-MWCNTs treatments. Increased biotransformation capacity at 18 °C and MIX treatment may explain lower caffeine concentration observed. At increased temperature differences among treatments were not so evident as at 18 °C, with a similar biological pattern among contaminated and control clams. Higher caffeine accumulation at MIX treatment under warming conditions may result from clams' inefficient biotransformation capacity when exposed to increased temperatures.
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Bivalvos , Nanotubos de Carbono , Contaminantes Químicos del Agua , Animales , Cafeína/toxicidad , Nanotubos de Carbono/toxicidad , Estrés Oxidativo , Temperatura , Contaminantes Químicos del Agua/toxicidadRESUMEN
Nowadays, multi-walled carbon nanotubes are considered to be emerging contaminants and their impact in ecosystem has drawn special research attention, while other contaminants, such as caffeine, have more coverage in literature. Despite this, the effects of a combination of the two has yet to be evaluated, especially considering predicted temperature rise. In the present study a typical bioindicator species for marine environment, the clam Ruditapes decussatus, and classical tools, such as biomarkers and histopathological indices, were used to shed light on the species' response to these contaminants, under actual and predicted warming scenarios. The results obtained showed that both contaminants have a harmful effect at tissue level, as shown by higher histopathological index, especially in digestive tubules. Temperatures seemed to induce greater biochemical impacts than caffeine (CAF) and -COOH functionalized multi-walled carbon nanotubes (f-MWCNTs) when acting alone, namely in terms of antioxidant defences and energy reserves content, which were exacerbated when both contaminants were acting in combination (MIX treatment). Overall, the present findings highlight the complex response of clams to both pollutants, evidencing the role of temperature on clams' sensitivity, especially to mixture of pollutants.
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Bivalvos , Nanotubos de Carbono , Contaminantes Químicos del Agua , Animales , Cafeína/toxicidad , Ecosistema , Nanotubos de Carbono/toxicidad , Estrés Oxidativo , Temperatura , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Computer-aided wet-spinning (CAWS) has emerged in the past few years as a hybrid fabrication technique coupling the advantages of additive manufacturing in controlling the external shape and macroporous structure of biomedical polymeric scaffold with those of wet-spinning in endowing the polymeric matrix with a spread microporosity. This book chapter is aimed at providing a detailed description of the experimental methods developed to fabricate by CAWS polymeric scaffolds with a predefined external shape and size as well as a controlled internal porous structure. The protocol for the preparation of poly(ε-caprolactone)-based scaffolds with a predefined pore size and geometry will be reported in detail as a reference example that can be followed and simply adapted to fabricate other kinds of scaffold, with a different porous structure or based on different biodegradable polymers, by applying the processing parameters reported in relevant tables included in the text.
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Diseño Asistido por Computadora , Microtecnología/métodos , Ingeniería de Tejidos/instrumentación , Andamios del Tejido/química , Implantes Absorbibles , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Durapatita/química , Humanos , Nanopartículas/química , Poliésteres/síntesis química , Poliésteres/química , Ingeniería de Tejidos/métodosRESUMEN
This work combines experimental and computational study of Balb/3T3 clone A31 mouse embryo fibroblasts cell line adhesion and proliferation on fourteen different polymeric surfaces prepared from poly(dioxanone) (PDO), poly(glycolic acid) (PGA), poly(hydroxybutyrate) (PHB), and poly(L-lactic acid) (PLA), and their 1:1 mixtures. The study was done with the aim to explore the attractive interactions between various synthetic biomaterials and simple model of the cell attachment mechanism involving the trans-membrane protein integrin. The considered polymeric biodegradable biomaterials can be used as scaffolds for tissue engineering and regenerative urology. During the growth of new tissue, the polymer scaffold is replaced by the extracellular matrix (ECM) synthetized by the proliferating cells. The adhesion and proliferation experiments were done on thin polymer films produced by solvent casting. The computational approach used 3D molecular models of two layers of ordered parallel polymeric fibres, which formed quasi-planar nanosized models of the scaffold surface. Experimental data showed that PGA based polymer films promote the cell adhesion. Cell proliferation testing, performed by incubating the fibroblast cells with the studied polymer films, disclosed that PLA, PHB/PLA and PHB/PGA systems are able to support proliferation of Balb/3T3 clone A31 cells equal to the plain glass. Relative interaction energies between 3D models of polymeric films and the α2 I domain of the cell adhesion receptor integrin α2ß1 computed by molecular mechanics suggest that plain polymers PGA, PDO and mixtures PDO/PGA, PHB/PGA, and especially PGA/PLA display elevated affinity to the cell-attachment protein, which confirms the experimental observations. The combination of experimental and modelling approach can assist rational design of synthetic polymeric biomaterial for scaffolds of artificial human urethra that can be efficiently colonized by cells.
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Medicina Regenerativa , Andamios del Tejido , Animales , Adhesión Celular , Fibroblastos , Humanos , Integrinas , Masculino , Ratones , Modelos Moleculares , Poliésteres , Polímeros , Prohibitinas , Ingeniería de Tejidos , UretraRESUMEN
The worldwide diffusion of nanotechnologies into products nowadays has completely revolutionized human life, providing novel comfort and benefits. Their inclusion in food and cosmetic has a heavy impact over the market, allowing the development of higher value products with enhanced properties. Natural origin polymers and in particular polysaccharides represent a versatile platform of materials for the development of micro/nanostructured additives for food and cosmetic products due to their chemical versatility, biocompatibility, and abundance. Here, we review the current applications of polysaccharides-based micro/nanostructures, taking into consideration the precursors' production, isolation, and extraction methods and highlighting the advantages, possible drawbacks, and market diffusion.
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Cosméticos/química , Aditivos Alimentarios/química , Nanoestructuras/química , Polisacáridos/química , Agaricales/química , Materiales Biocompatibles/química , Productos Biológicos/química , Celulosa/química , Mezclas Complejas/química , Grano Comestible/química , Humanos , Phaeophyceae/químicaRESUMEN
The use of carbon nanotubes (CNTs) is rapidly increasing and several scientific studies have addressed their toxicological properties. However, only a very small number of publications have deal with the interaction between CNTs and other molecules. Triclosan (TCS) is an antibacterial agent used in personal care and household products. Commonly detected in aquatic ecosystems, there is a strong evidence that aquatic biota is sensitive to this compound. Aside from emergent pollutants, aquatic organisms are continuously subjected to abiotic variations including salinities. Therefore, the main goal of the present study was to better understand how physio-chemical interactions of CNTs with TCS under different salinity levels (37, 28 and 19) affect the mussel species Mytilus galloprovincialis through the evaluation of biochemical alterations on gametes (sperms) and adult tissues, providing more ecologically relevant information on organisms' responses. The results showed toxicological effects in terms of sperm metabolic activity and intracellular reactive oxygen species production as well as cellular damage and alteration of metabolic capacity at the adult's stage when exposed to both contaminants acting alone and in combination, under tested salinities. Moreover, when the mussels were exposed to the combination of both contaminants, they showed major toxic impacts on both assessed biological levels (adult tissues and sperms) especially under control salinity. This suggests that toxicity upon mixture exposure compared to single-substance exposure may impair mussels' populations, affecting reproduction success and growth.
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Mytilus , Salinidad , Animales , Ecosistema , Masculino , Nanotubos de Carbono , Estrés Oxidativo , Espermatozoides , Triclosán , Contaminantes Químicos del AguaRESUMEN
A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron µ-vinyliminium precursors [Fe2Cp2(CO)( µ-CO){ µ-η1: η3-C3(R')C2HC1N(Me)(R)}]CF3SO3 (R = R' = Me, 1a; R = 2,6-C6H3Me2 = Xyl, R' = Ph, 1b; R = Xyl, R' = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a-d, 5a-b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.
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Antineoplásicos/síntesis química , Compuestos de Hierro/síntesis química , Neoplasias Ováricas/metabolismo , Selenio/química , Azufre/química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Teoría Funcional de la Densidad , Femenino , Células HEK293 , Humanos , Compuestos de Hierro/química , Compuestos de Hierro/farmacología , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Neoplasias Ováricas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Polymer microstructural engineering by additive manufacturing (AM) represents a powerful tool to functionalize tissue engineering scaffolds. This article reports on the processing of polymer/solvent/non-solvent ternary mixtures through their extrusion in a non-solvent bath as an innovative phase inversion-based AM approach to engineer poly(3-hydroxybutyrate-co-3-hydroxyexanoate) (PHBHHx) scaffolds porosity. The processing of PHBHHx mixtures with different chloroform/ethanol ratio into scaffolds characterized by a dual-scale porosity is described by highlighting how an interconnected network of macropores can be endowed with a tunable microporosity, formed a result of the phase inversion process governing polymer solidification. In particular, the study demonstrates that varying the non-solvent percentage in the ternary mixture represents an effective means to tailor the macropores size along scaffold vertical cross-section and the local micropores concentration in the polymer matrix. These structural changes are demonstrated to significantly affect scaffold overall porosity and tensile modulus, as well as its ability to support in vitro the proliferation of preosteoblast cells. The developed manufacturing strategy combines an advanced material engineering method effective on dual-scale size levels, with a modern approach to the sustainable processing of naturally-derived polyesters that minimizes the employment of halogenated solvents.
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Ácido 3-Hidroxibutírico/química , Caproatos/química , Andamios del Tejido/química , Ácido 3-Hidroxibutírico/farmacología , Animales , Caproatos/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Cloroformo/química , Etanol/química , Ratones , Porosidad , Ingeniería de TejidosRESUMEN
In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.