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We investigated online early comprehension in Italian children aged 12 and 20 months, focusing on the role of morphosyntactic features (i.e., gender) carried by determiners in facilitating comprehension and anticipating upcoming words. A naturalistic eye-tracking procedure was employed, recording looking behaviours during a classical Looking-While-Listening task. Children were presented with sentences and pictures of two objects representing nouns characterised by either the same gender (determiner was uninformative) or a different gender (determiner was informative). As expected, 20-month-old children recognised the target picture when this was named, and they were faster in the different-gender condition. Interestingly, 12-month-old infants identified the target picture only when presented with an informative determiner (different-gender condition). These results suggest that, as early as 12 months of age and with an improvement seen at 20 months of age, toddlers can extract and use determiner gender features to enhance comprehension and make predictions about upcoming words.
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Tecnología de Seguimiento Ocular , Desarrollo del Lenguaje , Humanos , Lactante , Lenguaje , Comprensión , Percepción AuditivaRESUMEN
A significant portion of the world's plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood-brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications.
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Amiloidosis , Contaminantes Químicos del Agua , Proteínas Amiloidogénicas , Amiloidosis/etiología , Animales , Humanos , Microplásticos , Plásticos , Pliegue de Proteína , Contaminantes Químicos del Agua/análisisRESUMEN
In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs' cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 µg/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.
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Nanopartículas de Magnetita , Nanopartículas , Nanopartículas de Magnetita/química , Albúmina Sérica Bovina , Hexanos , Medios de Contraste , Ácido Oléico , Medicina de Precisión , Ligandos , Heparina de Bajo-Peso-Molecular/farmacología , Dopamina , Sales (Química) , Compuestos Férricos/química , Nanopartículas/química , Heparina , Nanopartículas Magnéticas de Óxido de Hierro , Paclitaxel , Hierro , Agua , Carbodiimidas , AmidasRESUMEN
Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.
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Portadores de Fármacos/química , Compuestos Férricos/química , Heparina/química , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Transporte Biológico , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/metabolismo , Composición de Medicamentos/métodos , Liberación de Fármacos , Grasas/química , Compuestos Férricos/farmacología , Glicéridos/química , Heparina/metabolismo , Humanos , Absorción Intestinal , Modelos Biológicos , Nanopartículas/ultraestructura , Aceites/química , Tamaño de la Partícula , Electricidad Estática , Propiedades de SuperficieRESUMEN
Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe3O4·DA-BSA/HA in water. Fe3O4·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe3O4·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system.
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Albúminas/química , Antineoplásicos Fitogénicos/administración & dosificación , Portadores de Fármacos , Ácido Hialurónico/química , Nanopartículas de Magnetita/química , Paclitaxel/administración & dosificación , Espectroscopía de Resonancia Magnética con Carbono-13 , Humanos , Células MCF-7 , Microscopía Electrónica de Transmisión , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Heparin has been conjugated to Fe3O4, Co3O4, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin's ability to capture toluidine blue indicate that heparin's negative charges are exposed on the surface of the coated NPs. IR results confirmed the formation of nanohybrids as did NMR experiments, which were also interpreted on the basis of toluidine blue tests. Transmission electron microscopy results revealed that the heparin coating does not modify the shape or dimension of the NPs. Dynamic light scattering and negative zeta potential measurements confirmed that heparin surface functionalisation is an effective strategy to prevent NP aggregation.
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Metales Pesados/química , Nanopartículas/química , Óxidos/química , Coloides/química , Heparina , Nanopartículas/ultraestructura , Tamaño de la Partícula , Electricidad EstáticaRESUMEN
This manuscript describes the preparation and the spectroscopic characterisation of semi-synthetic sulfated maltotriose C-C linked dimers (SMTCs) where the natural C-O-C anomeric bond was substituted by one direct central C-C bond. This C-C bond induces conformation and flexibility changes with respect to the usual anomeric bond. SMTCs neutral precursors came from maltotriosyl bromide electroreduction through maltotriosyl radical intermediate dimerisation. The new C-C bond configuration, named for convenience α,α, α,ß and ß,ß as the natural anomeric bond, dictated the statistic ratio formation of three diastereoisomers. They were separated by silica gel flash chromatography followed by semi preparative HPLC chromatography. Each diastereoisomer was exhaustively sulfated to afford the corresponding SMTCs. SMTCs were huge characterised by NMR spectroscopy which provided the sulfation degree, too. α,α and α,ß were found quite homogeneous samples with a high degree of sulfation (85-95%). ß,ß appeared a non-homogeneous sample whose average sulfation degree was evaluated at around 78%. Mass spectroscopy experiments confirmed the sulfation degree range. Some considerations were proposed about SMTCs structure-biological properties.
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Antineoplásicos/química , Sulfatos/química , Trisacáridos/química , Antineoplásicos/síntesis química , Dimerización , Resonancia Magnética Nuclear Biomolecular , Trisacáridos/síntesis químicaRESUMEN
Cellulose derivatives have found significant applications in composite materials, mainly because of the increased mechanical performance they ensure. When added to cement-based materials, either in the form of nanocrystals, nanofibrils or micro/nanofibers, cellulose acts on the mixture with fresh and hardened properties, affecting rheology, shrinkage, hydration, and the resulting mechanical properties, microstructure, and durability. Commercial cotton wool was selected as starting material to produce multifunctional nanocelluloses to test as additives for mortars. Cotton wool was oxidized to oxidized nanocellulose (ONC), a charged nanocellulose capable of electrostatic interaction, merging cellulose and nanoparticles properties. Oxidized nanocellulose (ONC) was further functionalized by a radical-based mechanism with glycidyl methacrylate (GMA) and with a mixture of GMA and the crosslinking agent ethylene glycol dimethacrylate (EGDMA) affording ONC-GMA and ONC-GMA-EGDMA, both multifunctional-charged nanocellulose merging cellulose and bound acrylates properties. In this work, only ONC was found to be properly suitable for suspension and addition to a commercial mortar to assess the variation in mechanical properties and water-mortar interactions as a consequence of the modified microstructure obtained. The addition of oxidized nanocellulose caused an alteration of mortar porosity, with a decreased percentage of porosity and pore size distribution shifted towards smaller pores, with a consequent increase in compressive resistance, decrease in water absorption coefficient, and increased percentage of micropores present in the material, indicating a potential improvement in mortar durability.
RESUMEN
Irradiation of a number of different sutures largely employed in the clinical practice with either high energy electrons or with γ-rays followed by quenching with glycidyl methacrylate (GMA) conveniently led to derivatization through a radical-based process. The radicals involved were detected by means of ESR spectroscopy and were characterized on the basis of their ESR spectral parameters which were also found to be consistent with the hfs constants predicted by DFT calculations. Evidence of the GMA derivatization of the sutures was obtained via(13)C CP-MAS NMR spectroscopy, while its extent was evaluated gravimetrically.
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Compuestos Epoxi/química , Metacrilatos/química , Estructura MolecularRESUMEN
Nanocellulose (NC) is getting ahead as a renewable, biodegradable and biocompatible biomaterial. The NCs for this study were recovered from industrial cotton waste (CFT) by acid hydrolysis (HNC) and by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation (ONC). They were functionalized by radical based glycidyl methacrylate (GMA) grafting providing crystalline HNC-GMA and ONC-GMA, and by allylation (ALL) providing amorphous HNC-ALL and ONC-ALL. HNC, ONC and their derivatives were chemically and morphologically characterized. Crystalline NCs were found capable to adsorb, from diluted water solution (2 × 10-3 M), the antibiotics vancomycin (VC), ciprofloxacin (CP), amoxicillin (AM) and the disinfectant chlorhexidine (CHX), while amorphous NCs did not show any significant adsorption properties. Adsorption capability was quantified by measuring the concentration change in function of the contact time. The adsorption kinetics follow the pseudo-second order model and show complex adsorption mechanisms investigated by an intraparticle diffusion model and interpreted by structure-property relationships. ONC and ONC-GMA loaded with VC, and HNC and HNC-GMA loaded with CP were not colonized by Staphylococcus aureus and by Klebsiella pneumonia and suggested long lasting release capability. Our results can envisage developing CFT derived NCs for environmental applications (water remediation) and for biomedical applications (antibacterial NC). Among the future developments, it could also be of interest to take advantage of acidic, glycidyl and allyl groups' reactivity to provide other NCs from the NC object of this study.
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The electrochemical reduction on silver of peracetylated 6-iodo-6-deoxy-beta-maltose (2), 6-iodo-6-deoxy-beta-maltotriose (3) and 6'-iodo-6'-deoxy-beta-maltose (4) has been investigated by cyclic voltammetry and performed on a preparative scale, according to the stoichiometry, -CH(2)I(2-4) + e(-) --> -CH(2)(*) + I(-). In agreement with the preparative electrolysis results, cyclic voltammetry showed different profiles for the reducing terminal-iodinated 2 and 3 and for the non-reducing terminal-iodinated 4. Compounds 2 and 3 partly dimerised to maltotetraoses mimics 7 (6,6-dimer) and 8 (5',5'-dimer) in 38% overall yield and to maltohexaose mimics 12 (6,6-dimer) and 13 (5',5'-dimer) in 30% overall yield, respectively. Compounds 7 and 12 came from the dimerisation of -CH(2)(*), primary radicals at C-6, which could also abstract H-5', becoming CH(3) and generating the C-5' quaternary radicals that dimerised in 8 and 13, respectively. These products were accompanied by the maltose derivatives 9, 10 and 11 a/b in 42% overall yield and by the maltotriose derivatives 14, 15 and 16 in 48% overall yield, respectively. Compounds 9, 14 and 10, 15 came from -CH(2)(*) disproportionation to CH(3) and CH(2)=C, respectively (exocyclic double bond C-6/C-5). Compounds 11 a/b and 16 came from C-5' radical reduction, followed by acetate anion elimination (double bonds C-6'/C-5' and C-5'/C-4'). In turn, 4 afforded only the 6',6'-dimer maltotetraose mimic 17 in 60% yield, accompanied by the reduced maltose 18 in 20% yield, in which the starting CH(2)I became CH(3). Compounds 7, 8, 12, 13 and 17 belong to a class of mixed O/C malto-mimic oligosaccharides wherein an unnatural C-C bond between two saccharide units increases metabolic stability compared to their O-analogues and modulates the sugar chain conformational flexibility, a fundamental parameter in determining protein-carbohydrate binding. Direct and spin-trapping EPR studies substantiated the radical-based nature of the dimerisation processes and allowed the identification of some of the paramagnetic species involved.
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Maltosa/análogos & derivados , Maltosa/química , Modelos Moleculares , Secuencia de Carbohidratos , Electroquímica , Electrodos , Espectroscopía de Resonancia por Spin del Electrón , Estructura Molecular , Plata/química , EstereoisomerismoRESUMEN
Among nanocelluloses, bacterial nanocellulose (BNC) has proven to be a promising candidate in a range of biomedical applications, from topical wound dressings to tissue-engineering scaffolds. Chemical modifications and incorporation of bioactive molecules have been obtained, further increasing the potential of BNC. This study describes the incorporation of vancomycin and ciprofloxacin in BNC and in modified BNC to afford bioactive BNCs suitable for topical wound dressings and tissue-engineering scaffolds. BNC was modified by grafting glycidylmethacrylate (GMA) and further cross-linking with ethylene glycol dimethacrylate (EGDMA) with the formation of stable C-C bonds though a radical Fenton-type process that involves generation of cellulose carbon centred radicals scavenged by methacrylate structures. The average molar substitution degree MS (MS = methacrylate residue per glucose unit, measured by Fourier transform infrared (FT-IR) analysis) can be modulated in a large range from 0.1 up to 3. BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA maintain the hydrogel status until MS reaches the value of 1. The mechanical stress resistance increase of BNC-GMA and BNC-GMA-EGDMA of MS around 0.8 with respect to BNC suggests that they can be preferred to BNC for tissue-engineering scaffolds in cases where the resistance plays a crucial role. BNC, BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA were loaded with vancomycin (VC) and ciprofloxacin (CP) and submitted to release experiments. BNC-GMA-EGDMA of high substitution degree (0.7-1) hold up to 50 percentage of the loaded vancomycin and ciprofloxacin amount, suggesting that they can be further investigated for long-term antimicrobial activity. Furthermore, they were not colonized by Staphylococcus aureus (S.A.) and Klebsiella pneumonia (K.P.). Grafting and cross-linking BNC modification emerges from our results as a good choice to improve the BNC potential in biomedical applications like topical wound dressings and tissue-engineering scaffolds.
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The Fenton reaction as an oxidative degradation process was used for industrial chemical wastewater (ICW) pretreatment. The biodegradation of pretreated ICW was performed, in aqueous environment under aerobic condition, by a defined fungal consortium. The central composite design (CCD) was used to study the effect of nitrogen and phosphorus addition and the concentration of the pollution on the removal of polyvinyl alcohol (PVA) and organic compounds. The interaction between parameters was modeled using the response surface methodology (RSM). Results of optimization showed COD, PVA and color removal yields of 97.8%, 98.5% and 99.75%, respectively with a supplementof 1.4â¯gL-1 of (NH4)2SO4, 1.2â¯gL-1 of KH2PO4 and 75% of concentrated ICW. Enzymatic analysis proved that laccase and lignin peroxidase were involved in the biodegradation with 45 UIL-1 and 450 UIL-1, respectively. Furthermore, the analysis of metabolic products using Fourier transforms infrared spectroscopy (FTIR) and nuclear magnetic resonance (1HNMR) showed clearly the mineralization of organic compounds and the formation of formic acid and ethanol. Therefore, the effective treatment of ICW was achieved by developing an integrated chemical and biological process which met the requirement for a safety effluent respectful for environment without risks for public health.
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Hongos/crecimiento & desarrollo , Peróxido de Hidrógeno/química , Hierro/química , Polivinilos/análisis , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Aspergillus/crecimiento & desarrollo , Biodegradación Ambiental , Chaetomium/crecimiento & desarrollo , Residuos Industriales/análisis , Consorcios Microbianos , Rhizopus/crecimiento & desarrolloRESUMEN
This work describes the structure of a fully sulfated maltotriose alpha-beta C-C linked dimer, where a central glycosidic bond was substituted by a non natural, hydrolase-resistant C-C bond. Such compound shows anti-metastatic properties being an inhibitor of the heparanase enzymatic activity and of P-selectin-mediated cell-cell interactions. NMR spectroscopy was applied to investigate the structure and conformational properties of this C-C linked hexasaccharide. The presence of sulfate substituents and the internal C-C bond drives the two internal rings in an unusual (1)C(4) chair conformation, while the external rings linked by glycosidic bonds retain the typical (4)C(1) conformation. The NMR results were confirmed by molecular mechanics calculations using structure corresponding di- and tetrasaccharides as models.
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Glucosa/química , Oligosacáridos/química , Sulfatos/química , Conformación de Carbohidratos , Dimerización , Modelos MolecularesRESUMEN
High-grade cellulose (97% α-cellulose content) of 48% crystallinity index was extracted from the renewable marine biomass waste Posidonia oceanica using H2O2 and organic peracids following an environmentally friendly and chlorine-free process. This cellulose appeared as a new high-grade cellulose of waste origin quite similar to the high-grade cellulose extracted from more noble starting materials like wood and cotton linters. The benefits of α-cellulose recovery from P. oceanica were enhanced by its transformation into cellulose acetate CA and cellulose derivative GMA-C. Fully acetylated CA was prepared by conventional acetylation method and easily transformed into a transparent film. GMA-C with a molar substitution (MS) of 0.72 was produced by quenching Fenton's reagent (H2O2/FeSO4) generated cellulose radicals with GMA. GMA grafting endowed high-grade cellulose from Posidonia with adsorption capability. GMA-C removes ß-naphthol from water with an efficiency of 47%, as measured by UV-Vis spectroscopy. After hydrolysis of the glycidyl group to glycerol group, the modified GMA-C was able to remove p-nitrophenol from water with an efficiency of 92%, as measured by UV-Vis spectroscopy. α-cellulose and GMA-Cs from Posidonia waste can be considered as new materials of potential industrial and environmental interest.
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In the search for noninvasive diagnostic techniques and new therapies, "nanosystems", which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics.
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Quitosano/análogos & derivados , Heparina/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Materiales Biocompatibles , Línea Celular , Supervivencia Celular/efectos de los fármacos , Quitosano/administración & dosificación , Quitosano/toxicidad , Portadores de Fármacos , Heparina/toxicidad , Humanos , Hierro/química , Nanopartículas del Metal/toxicidad , Microscopía Electrónica de Transmisión , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad EstáticaRESUMEN
Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation.
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Glucuronidasa/antagonistas & inhibidores , Neoplasias/patología , Oligosacáridos/farmacología , Selectina-P/antagonistas & inhibidores , Sulfatos/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Endotelio Vascular/fisiología , Ensayo de Inmunoadsorción Enzimática , Glucuronidasa/biosíntesis , Glicósido Hidrolasas/biosíntesis , Glicósido Hidrolasas/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Neoplasias/metabolismo , Selectina-P/biosíntesis , Microambiente TumoralRESUMEN
Hydrogen peroxide (H2O2) and Cu(OAc)2 or FeSO4 (Fenton type reagents) perform heparin (Hep) depolymerisation to low-molecular-weight heparin (LMWH) following a radical chain mechanism. Hydroxyl (OH) radicals which are initially generated from H2O2 reduction by transition metal ions abstract hydrogen atoms on the heparin chain providing carbon centred radicals whose decay leads to the depolymerisation process. The main depolymerisation mechanism involves Hep radical intermediates that cleave the glycosidic linkage at unsulphated uronic acids followed by a 6-O-nonsulphated glucosamine, thus largely preserving the pentasaccharide sequence responsible for the binding to antithrombin III (AT). Both the transition metal ions influence the overall efficiency of the radical chain processes: Fe2+ acting as a catalyst, while Cu2+ acts as a reagent. LMWHs, especially those afforded by Cu2+, are somewhat unstable to the usual basic workup. However, this lack of stability can be eliminated by a previous NaBH4 reduction. Furthermore, with Cu2+, the process is much more reproducible than with Fe2+. Therefore, for the process of Fenton type depolymerisation of heparin, the use of Cu(OAc)2 is clearly preferable to the more "classical" FeSO4. The resulting activities and characteristics of these LMWHs are peculiar to these oxidative radical processes. In addition, LMWH provided by H2O2/Cu(OAc)2 in optimised conditions was found to posses anti-Xa and anti-IIa activities comparable to those of LMWHs currently in clinical use.
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Heparina de Bajo-Peso-Molecular/síntesis química , Peróxido de Hidrógeno/química , Hierro/química , Animales , Cobre , Inhibidores del Factor Xa , Heparina/química , Heparina de Bajo-Peso-Molecular/farmacología , Humanos , Protrombina/antagonistas & inhibidores , PorcinosRESUMEN
Cellulose material C1 was prepared by grafting of glycidyl methacrylate (GMA) in the presence of Fenton-type reagent. This one-pot procedure provided C1 with glycidyl isobutyrate branches. Glycidyl epoxide ring opening with water turned C1-C2 material branched with glycerol isobutyrate. So, C1 surface bears hydrophobic branches ending with the glycidyl group, while C2 surface presents hydrophilic branches ending with the glycerol group. The adsorption of aromatic polluting substances like phenol (Ph), 4-nitrophenol (pNPh), 2,4-dinitrophenol (dNPh), 2,4,6-trinitrophenol (picric acid, tNPh) and 2-naphtol (BN) from their water solutions was tested with C1, C2 and with the untreated cellulose material C0. Phenol adsorption did not occur. All the other aromatic molecules were removed in different amount both by C1 and C2. C1 and C2 showed different affinities towards nitrophenols and 2-naphtol. While C1 was much more effective for removing the hydrophobic 2-naphtol, C2 had higher adsorption capacity towards the hydrophilic nitrophenols, in agreement with their branches polarity, respectively.
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Celulosa/química , Fibra de Algodón , Compuestos Epoxi/química , Gossypium/química , Hidrocarburos Aromáticos/química , Metacrilatos/química , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisis , Adsorción , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Cinética , Espectroscopía de Resonancia Magnética , Fenoles/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Temperatura , TermodinámicaRESUMEN
A low molecular weight heparin (LMWH) obtained by a depolymerization process induced by a Fenton-type reagent was characterized in depth by nuclear magnetic resonance (NMR) spectroscopy. The depolymerization involves the cleavage of glycosidic bonds, leading to natural terminal reducing end residues, mainly represented by N-sulfated glucosamine (A (NS)). Natural uronic acids, especially the 2- O-sulfate iduronic acid (I (2S)), are also present as reducing residues. A peculiar reaction results, such as the disappearance of the nonsulfated iduronic acid residues when followed by 6-O-nonsulfated glucosamine, and the decrease of the glucuronic acid when followed by the N-acetylglucosamine, were observed. Iduronic acid residues, followed by 6- O-sulfate glucosamine (A (Nx,6S)), and the glucuronic acid residues, followed by A (NS) residues, were not modified. A few minor internal chain modifications occur, possibly arising from oxidative breaking of the bond between C2-C3 of glucosamine and uronic acids, suggested by evidence of formation of new -COR groups. Finally, no change was observed in the content of the N-sulfated, 6-O-sulfated glucosamine bearing an extra sulfate on 3-O, which is considered the marker of the active site for antithrombin. With respect to the original heparin, this LMWH is characterized by a lower number of nonsulfated uronic acid residues, and as a consequence, by a lower degree of structural heterogeneity than LMWHs prepared with other procedures.