ABSTRACT
The 10-23 DNAzyme, a catalytic DNA molecule with RNA-cleaving activity, has garnered significant interest for its potential therapeutic applications as a gene-silencing agent. However, the lack of a detailed understanding about its mechanism has hampered progress. A recent structural analysis has revealed a highly organized conformation thanks to the stabilization of specific interactions within the catalytic core of the 10-23 DNAzyme, which facilitate the cleavage of RNA. In this configuration, it has been shown that G14 is in good proximity to the cleavage site which suggests its role as a general base, by activating the 2'-OH nucleophile, in the catalysis of the 10-23 DNAzyme. Also, the possibility of a hydrated metal acting as a general acid has been proposed. In this study, through activity assays, we offer evidence of the involvement of general acid-base catalysis in the mechanism of the 10-23 DNAzyme by analyzing its pH-rate profiles and the role of G14, and metal cofactors like Mg2+ and Pb2+. By substituting G14 with its analogue 2-aminopurine and examining the resultant pH-rate profiles, we propose the participation of G14 in a catalytically relevant proton transfer event, acting as a general base. Further analysis, using Pb2+ as a cofactor, suggests the capability of the hydrated metal ion to act as a general acid. These functional results provide critical insights into the catalytic strategies of RNA-cleaving DNAzymes, revealing common mechanisms among nucleic acid enzymes that cleave RNA.
Subject(s)
DNA, Catalytic , DNA, Catalytic/chemistry , DNA, Catalytic/metabolism , Hydrogen-Ion Concentration , Biocatalysis , Kinetics , Magnesium/chemistry , Magnesium/metabolism , Catalysis , Lead/chemistry , Lead/metabolism , DNA, Single-StrandedABSTRACT
Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.
Subject(s)
Antineoplastic Agents , Curcumin , Curcumin/analogs & derivatives , Magnesium , beta-Cyclodextrins , beta-Cyclodextrins/chemistry , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/pharmacokinetics , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Magnesium/chemistry , Apoptosis/drug effects , Female , Cell Line, Tumor , STAT3 Transcription Factor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Cell Movement/drug effects , Solubility , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Chick Embryo , Matrix Metalloproteinase 9/metabolismABSTRACT
This study describes the production, characterization and application of an endoglucanase from Penicillium roqueforti using lignocellulosic agro-industrial wastes as the substrate during solid-state fermentation. The endoglucanase was generated after culturing with different agro-industrial wastes for 96 h without any pretreatment. The highest activity was obtained at 50 °C and pH 4.0. Additionally, the enzyme showed stability in the temperature and pH ranges of 40-80 °C and 4.0-5.0, respectively. The addition of Ca2+, Zn2+, Mg2+, and Cu2+ increased enzymatic activity. Halotolerance as a characteristic of the enzyme was confirmed when its activity increased by 35% on addition of 2 M NaCl. The endoglucanase saccharified sugarcane bagasse, coconut shell, wheat bran, cocoa fruit shell, and cocoa seed husk. The Box-Behnken design was employed to optimize fermentable sugar production by evaluating the following parameters: time, substrate, and enzyme concentration. Under ideal conditions, 253.19 mg/g of fermentable sugars were obtained following the saccharification of wheat bran, which is 41.5 times higher than that obtained without optimizing. This study presents a thermostable, halotolerant endoglucanase that is resistant to metal ions and organic solvents with the potential to be applied in producing fermentable sugars for manufacturing biofuels from agro-industrial wastes.
Subject(s)
Cellulase , Saccharum , Cellulase/chemistry , Cellulose , Dietary Fiber , Fermentation , Industrial Waste , Research Design , Saccharum/metabolism , Sugars , Calcium/chemistry , Copper/chemistry , Zinc/chemistry , Magnesium/chemistryABSTRACT
This study was dedicated to developing analytical methods for determining macronutrients (Ca, K, and Mg) in soy leaf samples with and without petioles. The study's primary purpose was to present Laser-induced breakdown spectroscopy (LIBS) as a viable alternative for directly analyzing leaf samples using chemometric tools to interpret the data obtained. The instrumental condition chosen for LIBS was 70â mJ of laser pulse energy, 1.0â µs of delay time, and 100â µm of spot size, which was applied to 896 samples: 305 of soy without petioles and 591 of soy with petioles. The reference values of the analytes for the proposition of calibration models were obtained using inductively coupled plasma optical emission spectroscopy (ICP-OES) technique. Twelve normalization modes and two calibration strategies were tested to minimize signal variations and sample matrix microheterogeneity. The following were studied: multivariate calibration using partial least squares and univariate calibration using the area and height of several selected emission lines. The notable normalization mode for most models was the Euclidean norm. No analyte showed promising results for univariate calibrations. Micronutrients, P and S, were also tested, and no multivariate models presented satisfactory results. The models obtained for Ca, K, and Mg showed good results. The standard error of calibration ranged from 2.3â g/kg for Ca in soy leaves without petioles with two latent variables to 5.0â g/kg for K in soy leaves with petioles with two latent variables.
Subject(s)
Lasers , Photoelectron Spectroscopy/methods , Spectrum Analysis/methods , Calcium/analysis , Calcium/chemistry , Potassium/analysis , Potassium/chemistry , Magnesium/analysis , Magnesium/chemistryABSTRACT
The effect of unidirectional and cross rolling on the corrosion rate, texture, tensile properties and hemolysis of the Mg-0.375Ga and Mg-0.750Ga alloys was evaluated. Pure Mg and as-cast alloys were processed by unidirectional and cross rolling at 400°C to obtain a total thickness reduction of 50%. The corrosion rate was measured by the weight loss method in simulated body fluid. Determination of the hemolysis percentage was carried out by direct contact of specimens with diluted blood. After hot rolling, the mechanical properties of the alloys were improved. The cross-rolled Mg-0.750Ga alloy showed the highest grain refinement (55 µm) and the highest ultimate tensile strength (240 MPa), however, lower elongation (13.9%) than the rolled Mg-0.375Ga alloy. While unidirectional rolling creates a strong basal texture, cross rolling weakens considerably this texture. The Ga addition weakens the basal texture. Corrosion rate of the Mg-Ga alloys was significantly reduced (<1 mm/yr) after heat treatment and hot rolling due the homogenization of the microstructure and the presence of gallium as alloying element. The cross-rolled samples showed higher corrosion than the heat-treated and unidirectionally rolled samples. After rolling, alloys showed hemolysis percentages between 7.1 and 9.3%, values lower than those presented by pure magnesium (>22.7%) and as-cast alloys (>24.2%); however, the alloys are still hemolytic (>5%).
Subject(s)
Alloys , Magnesium , Alloys/chemistry , Biocompatible Materials/chemistry , Corrosion , Magnesium/chemistry , Materials Testing , Tensile StrengthABSTRACT
Human 71 kDa heat shock cognate protein (HSPA8, also known as Hsc70, Hsp70-8, Hsc71, Hsp71 or Hsp73) is a constitutively expressed chaperone that is critical for cell proteostasis. In the cytosol, HSPA8 plays a pivotal role in folding and refolding, facilitates protein trafficking across membranes and targets proteins for degradation, among other functions. Here, we report an in solution study of recombinant HSPA8 (rHSPA8) using a variety of biophysical and biochemical approaches. rHSPA8 shares several structural and functional similarities with others human Hsp70s. It has two domains with different stabilities and interacts with adenosine nucleotides with dissociation constants in the low micromolar range, which were higher in the presence of Mg2+. rHSPA8 showed lower ATPase activity than its homolog HSPA5/hGrp78/hBiP, but it was 4-fold greater than that of recombinant HSPA1A/hHsp70-1A, with which it is 86% identical. Small angle X-ray scattering indicated that rHSPA8 behaved as an elongated monomeric protein in solution with dimensions similar to those observed for HSPA1A. In addition, rHSPA8 showed structural flexibility between its compacted and extended conformations. The data also indicated that HSPA8 has capacity in preventing the aggregation of model client proteins. The present study expands the understanding of the structure and activity of this chaperone and aligns with the idea that human homologous Hsp70s have divergent functions.
Subject(s)
HSC70 Heat-Shock Proteins/chemistry , Adenosine Triphosphate/chemistry , Adenosine Triphosphate/metabolism , HSC70 Heat-Shock Proteins/metabolism , Humans , Magnesium/chemistry , Magnesium/metabolism , Molecular Dynamics Simulation , Protein Domains , Protein FoldingABSTRACT
Decapod crustaceans show variable degrees of euryhalinity and osmoregulatory capacity, by responding to salinity changes through anisosmotic extracellular regulation and/or cell volume regulation. Cell volume regulatory mechanisms involve exchange of inorganic ions between extra- and intra-cellular (tissue) compartments. Here, this interplay of inorganic ions between both compartments has been evaluated in four decapod species with distinct habitats and osmoregulatory strategies. The marine/estuarine species Litopenaeus vannamei (Lv) and Callinectes danae (Cd) were submitted to reduced salinity (15), after acclimation to 25 and 30, respectively. The freshwater Macrobrachium acanthurus (Ma) and Aegla schmitti (As) were submitted to increased salinity (25). The four species were salinity-challenged for both 5 and 10 days. Hemolymph osmolality, sodium, chloride, potassium, and magnesium were assayed. The same inorganic ions were quantified in muscle samples. Muscle hydration (MH) and ninhydrin-positive substances (NPS) were also determined. Lv showed slight hemolymph dilution, increased MH and no osmotically-relevant decreases in muscle osmolytes; Cd displayed hemolymph dilution, decreased muscular NaCl and stable MH; Ma showed hypo-regulation and steady MH, with no change in muscle ions; As conformed hemolymph sodium but hypo-regulated chloride, had stable MH and increased muscle NPS and ion levels. Hemolymph and muscle ions (especially chloride) of As were highly correlated (Pearson, +0.83). Significant exchanges between hemolymph and muscle ionic pools were more evident in the two species with comparatively less AER regulatory power, C. danae and A. schmitti. Our findings endorse that the interplay between extracellular and tissue ionic pools is especially detectable in euryhaline species with relatively lower osmoregulatory strength.
Subject(s)
Decapoda/physiology , Ions/metabolism , Osmoregulation , Palaemonidae/metabolism , Penaeidae/physiology , Animals , Cadmium/metabolism , Hemolymph , Magnesium/chemistry , Osmolar Concentration , Potassium/chemistry , Salinity , Sodium Chloride/chemistry , Species Specificity , Water-Electrolyte Balance/physiologyABSTRACT
Fluxes between fractured-karstified and detritic aquifers are commonly poorly understood in many environments. These two types of aquifers are in contact in the southeastern Pampean region in the Argentine Buenos Aires province, and the aim of this work is to analyze their relationship contributing to improve the hydrological model. A joint application of hydrochemical and multi-isotope (δ 2H, δ 18O, δ 13C-TDIC, δ 18O-TDIC, 87Sr/86Sr) tools was used. TDIC, δ 2H, δ 18O and δ 13C-TDIC allowed differentiating two main end members. Water in the Pampeano aquifer (PA) which is transferred from the fractured-karstic aquifer (F-KA) is characterised by high TDIC around 500-700â mg/L, isotopically depleted in 18O (about -5.5 ) and high δ 13C-TDIC (around -10.0 ). The other end member is direct recharge water infiltrated into the PA with TDIC ranging from 400 to 500â mg/L, slightly enriched in 18O (δ 18O = -4.8 ), and δ 13C-TDIC in the range of soil CO2 as a result of reactions with calcrete concretions (from -20.0 to -9.0 ). Dolomite dissolution is the main process controlling the chemistry of the low-mineralized (Mg-Ca-HCO3) waters, whereas high-mineralized (Na-HCO3) waters are strongly influenced by ion-exchange reactions with adsorbed Ca2+ and Mg2+ and by evaporation.
Subject(s)
Environmental Monitoring/methods , Groundwater/chemistry , Isotopes/analysis , Argentina , Calcium Carbonate/chemistry , Magnesium/chemistry , Solubility , Water CycleABSTRACT
Spittlebugs are the main pest of tropical pastures and Marandu palisade grass (Urochloa brizantha cv. Marandu) is the most representative cultivated pasture in the tropics. Our objective was to characterize Marandu palisade grass responses subjected to Mahanarva (Hemiptera: Cercopidae) attack and to estimate the losses in terms of beef production from pasture-based systems. A set of five experiments were carried out. Three consecutive years of monitoring showed that Mahanarva spittlebugs increased their abundance after first rains with three to four peaks throughout the wet season. A decrease of 66% on herbage yield was observed in the greenhouse trial, with an average decrease of 61% on pools of calcium, magnesium, phosphorus, sulfur, potassium, crude protein, neutral-detergent fiber and in vitro digestible dry matter of Marandu palisade grass. Results from field experiments corroborated with greenhouse trial showing decreases on herbage yield varying from 31 to 43% depending on level of fertilization and grazing severity of Marandu palisade grass. Finally, an unprecedented 154-ha field experiment indicated that Mahanarva decreases 74% the beef productivity (i.e. kg body weight ha-1) of Nellore heifers grazing Marandu palisade grass.
Subject(s)
Animal Feed , Hemiptera/physiology , Poaceae , Animal Husbandry , Animals , Calcium/chemistry , Cattle , Entomology , Female , Linear Models , Magnesium/chemistry , Nutritive Value , Phosphorus/chemistry , Photosynthesis , Rain , Red Meat , Seasons , Sulfur/chemistryABSTRACT
Hsp90 is a ubiquitous, homodimer and modular molecular chaperone. Each Hsp90 protomer has three different domains, named the N-terminal domain (NTD), middle domain (MD) and C-terminal domain (CTD). The Hsp90 molecular cycle involves ATP binding and hydrolysis, which drive conformational changes. Hsp90 is critical for the viability of eukaryotic organisms, including the protozoan that causes the severe form of malaria, Plasmodium falciparum, the growth and differentiation of which are compromised when Hsp90 is inhibited. Here, we characterize the structure of a recombinant P. falciparum Hsp90 (PfHsp90) protein, as well as its MD (PfHsp90MD) and NTD plus MD (PfHsp90NMD) constructs. All the proteins were obtained with high purity and in the folded state. PfHsp90 and PfHsp90NMD interacted with adenosine nucleotides via the NTD, and Mg2+ was critical for strong binding. PfHsp90 behaved mostly as elongated and flexible dimers in solution, which dissociate with a sub-micromolar dissociation constant. The PfHsp90MD and PfHsp90NMD constructs behaved as globular and elongated monomers, respectively, confirming the importance of the CTD for dimerization. Small angle X-ray scattering data were obtained for all the constructs, and ab initio models were constructed, revealing PfHsp90 in an open conformation and as a greatly elongated and flexible protein.
Subject(s)
HSP90 Heat-Shock Proteins/chemistry , Plasmodium falciparum/chemistry , Protozoan Proteins/chemistry , Recombinant Proteins/chemistry , Adenosine/chemistry , Adenosine Triphosphate/chemistry , Binding Sites , Cross-Linking Reagents/chemistry , Crystallography, X-Ray , Hydrolysis , Magnesium/chemistry , Models, Molecular , Protein Binding , Protein Conformation , Protein MultimerizationABSTRACT
The influence of magnesium on roasting vanadium slag was investigated by simulating the roasting process of vanadium by mixing V2O5 and MgO. The calcination products of V2O5 reacted with MgO at different temperatures which were characterized by X-ray diffraction (XRD), Thermogravimetry-differential scanning calorimetry (TG-DSC) and scanning electron microscope (SEM). There were two mass loss intervals, three endothermic peaks and one exothermic peak appearing during the reaction by the integrated thermal analysis as the temperature increased from room temperature to 1273.15 K. The samples of mixed V2O5 and MgO began to melt at 573.15 K and reacted at 773 K, and the shape of the particles changed from block to ovoid or irregular sphere at 773.15 K. With increasing the reaction temperature from 973.15 to 1073.15 K, the intermediate of VO2 was produced, and MgV2O6 was partially decomposed at 1073.15 K. During this process, the particle shape gradually returned to block shape. The conversion rate of vanadium is 99.4% with MgO of 1.65%.
Subject(s)
Magnesium/chemistry , Calorimetry, Differential Scanning , Minerals , Thermogravimetry , VanadiumABSTRACT
We provide a kinetic characterization of (Na+, K+)-ATPase activity in a posterior gill microsomal fraction from the grapsid crab Goniopsis cruentata. (Na+, K+)-ATPase activity constitutes 95% of total ATPase activity, and sucrose density centrifugation reveals an ATPase activity peak between 25 and 35% sucrose, distributed into two, partially separated protein fractions. The (Na+, K+)-ATPase α-subunit is localized throughout the ionocyte cytoplasm and has an Mr of ≈ 10 kDa and hydrolyzes ATP obeying cooperative kinetics. Low (VM = 186.0 ± 9.3 nmol Pi min-1 mg-1 protein and K0.5 = 0.085 ± 0.004 mmol L-1) and high (VM = 153.4 ± 7.7 nmol Pi min-1 mg-1 protein and K0.5 = 0.013 ± 0.0006 mmol L-1) affinity ATP binding sites were characterized. At low ATP concentrations, excess Mg2+ stimulates the enzyme, triggering exposure of a high-affinity binding site that accounts for 50% of (Na+, K+)-ATPase activity. Stimulation by Mg2+ (VM = 425.9 ± 25.5 nmol Pi min-1 mg-1 protein, K0.5 = 0.16 ± 0.01 mmol L-1), K+ (VM = 485.3 ± 24.3 nmol Pi min-1 mg-1 protein, K0.5 = 0.9 ± 0.05 mmol L-1), Na+ (VM = 425.0 ± 23.4 nmol Pi min-1 mg-1 protein, K0.5 = 5.1 ± 0.3 mmol L-1) and NH4+ (VM = 497.9 ± 24.9 nmol Pi min-1 mg-1 protein, K0.5 = 9.7 ± 0.5 mmol L-1) obeys cooperative kinetics. Ouabain inhibits up to 95% of ATPase activity with KI = 196.6 ± 9.8 µmol L-1. This first kinetic characterization of the gill (Na+, K+)-ATPase in Goniopsis cruentata enables better comprehension of the biochemical underpinnings of osmoregulatory ability in this semi-terrestrial mangrove crab.
Subject(s)
Brachyura/metabolism , Chemical Phenomena , Gills/metabolism , Magnesium/chemistry , Magnesium/metabolism , Sodium-Potassium-Exchanging ATPase/chemistry , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Enzyme Activation , Microsomes , PhosphorylationABSTRACT
Abstract Background: Different mechanical properties have been suggested for metallic bioresorbable vascular scaffolds (BVS) in comparison to polymeric BVS. We aim to evaluate the acute mechanical performance of Magmaris® scaffold in comparison to Absorb®. Materials and Methods: Two groups of 10 coronary lesions treated with Magmaris® and Absorb® 1.1 (20584 vs. 21016 struts) were compared. In all cases, optical coherence tomographic (OCT) images were acquired after scaffold deployment. Baseline clinical, angiographic, and procedural characteristics were compared, including OCT evaluations. Results: No baseline clinical or angiographic significant differences were found between groups. The most common indication for revascularization was effort angina (60% vs. 70% p = 0.45) with no ST-elevation myocardial infarction (MI) cases. Main target artery was left anterior descending, with a mean vessel diameter of 3.46 ± 0.23 in Absorb® and 3.52 ± 0.19mm in Magmaris® groups (p = 0.56). All cases underwent pre- and post-dilatation with a procedural success rate of 100%. OCT analyses showed larger scaffold and vessel diameters in Magmaris® group: 3.11 ± 0.38 mm versus 3.07 ± 0.36 mm, p = 0.03 and 4.12 ± 0.51 mm versus 4.04 ± 0.46 mm, p = 0.04. Despite the application of slightly higher postdilatation pressures to Magmaris® devices (18.01 ± 2.15 vs. 17.20 ± 3.80 atm, p = 0.05), significantly lower percentages of disrupted and malapposed struts were identified within Magmaris® scaffolds (0.15% vs. 0.27%, p = 0.03 and 1.06% vs. 1.46% p = 0.01). No cardiac death, target vessel-related MI, or clinically driven target lesion revascularization was reported in a 30-day follow-up. Conclusion: Mechanical properties of Magmaris® scaffold allow achieving larger vessel and scaffold diameters in a safe manner, with lower rates of malapposition and scaffold disruption.
Resumen Introducción: Se ha sugerido la presencia de un distinto comportamiento mecánico entre los dos grupos principales de dispositivos bioresorbibles: metálicos y poliméricos. En este estudio evaluamos el comportamiento mecánico agudo del andamiaje bioresorbible metálico Magmaris® frente al del polimérico Absorb®. Métodos: Se compararon dos grupos de 10 lesiones coronarias tratadas con Magmaris® y Absorb® 1.1 (20584 vs. 21016 struts). En todos los casos se realizó estudio postimplante del dispositivo mediante tomografia de coherencia óptica (OCT). Se compararon las características basales clínicas y angiográficas, así como aspectos del procedimiento (incluídos los estudios de OCT) entre ambos grupos. Resultados: No se encontraron diferencias clínicas o angiográficas estadísticamente significativas entre ambos grupos. La indicación más frecuente de revascularización coronaria fué la presencia de angina de esfuerzo (60% vs. 70% p = 0.45), sin incluirse casos de IAMCEST. La arteria descendente anterior fué el principal vaso diana, con un diámetro medio de 3.46 ± 0.23 mm en el grupo de Absorb® y de 3.52 ± 0.19mm en el grupo de Magmaris® (p = 0.56). En todos los casos se realizó pre y postdilatación, con una tasa de éxito del procedimiento del 100%. Los estudios mediante OCT demostraron un mayor diámetro de stent y del vaso en el grupo de Magmaris®: 3.11 ± 0.38mm versus 3.07 ± 0.36 mm, p = 0.03 y 4.12 ± 0.51mm versus 4.04 ± 0.46mm, p = 0.04. A pesar de someter a los dispositivos Magmaris® a presiones de postdilatación ligeramente superiores (18.01 ± 2.15 vs. 17.20 ± 3.80 atm, p = 0.05), se identificó un menor porcentaje estadísticamente significativo de struts rotos o malapuestos en dicho grupo (0.15% vs. 0.27 %, p = 0.03 y 1.06 % vs. 1.46% p = 0.01). En un seguimiento a 30 días no se registraron eventos mayores: muerte cardíaca, IM relacionado con vaso diana o TLR. Conclusión: Las propiedades mecánicas del scaffold metálico bioresorbible Magmaris® permiten alcanzar mayores diámetros de stent y vaso de forma segura tras su implante, con una baja tasa de malaposición y disrupción.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Coronary Artery Disease/surgery , Absorbable Implants , Tissue Scaffolds , Drug-Eluting Stents , Polyesters/chemistry , Prosthesis Design , Coronary Artery Disease/diagnostic imaging , Retrospective Studies , Treatment Outcome , Coronary Angiography , Tomography, Optical Coherence , Magnesium/chemistryABSTRACT
Background: Different mechanical properties have been suggested for metallic bioresorbable vascular scaffolds (BVS) in comparison to polymeric BVS. We aim to evaluate the acute mechanical performance of Magmaris® scaffold in comparison to Absorb®. Materials and Methods: Two groups of 10 coronary lesions treated with Magmaris® and Absorb® 1.1 (20584 vs. 21016 struts) were compared. In all cases, optical coherence tomographic (OCT) images were acquired after scaffold deployment. Baseline clinical, angiographic, and procedural characteristics were compared, including OCT evaluations. Results: No baseline clinical or angiographic significant differences were found between groups. The most common indication for revascularization was effort angina (60% vs. 70% p = 0.45) with no ST-elevation myocardial infarction (MI) cases. Main target artery was left anterior descending, with a mean vessel diameter of 3.46 ± 0.23 in Absorb® and 3.52 ± 0.19mm in Magmaris® groups (p = 0.56). All cases underwent pre- and post-dilatation with a procedural success rate of 100%. OCT analyses showed larger scaffold and vessel diameters in Magmaris® group: 3.11 ± 0.38 mm versus 3.07 ± 0.36 mm, p = 0.03 and 4.12 ± 0.51 mm versus 4.04 ± 0.46 mm, p = 0.04. Despite the application of slightly higher postdilatation pressures to Magmaris® devices (18.01 ± 2.15 vs. 17.20 ± 3.80 atm, p = 0.05), significantly lower percentages of disrupted and malapposed struts were identified within Magmaris® scaffolds (0.15% vs. 0.27%, p = 0.03 and 1.06% vs. 1.46% p = 0.01). No cardiac death, target vessel-related MI, or clinically driven target lesion revascularization was reported in a 30-day follow-up. Conclusion: Mechanical properties of Magmaris® scaffold allow achieving larger vessel and scaffold diameters in a safe manner, with lower rates of malapposition and scaffold disruption.
Introducción: Se ha sugerido la presencia de un distinto comportamiento mecánico entre los dos grupos principales de dispositivos bioresorbibles: metálicos y poliméricos. En este estudio evaluamos el comportamiento mecánico agudo del andamiaje bioresorbible metálico Magmaris® frente al del polimérico Absorb®. Métodos: Se compararon dos grupos de 10 lesiones coronarias tratadas con Magmaris® y Absorb® 1.1 (20584 vs. 21016 struts). En todos los casos se realizó estudio postimplante del dispositivo mediante tomografia de coherencia óptica (OCT). Se compararon las características basales clínicas y angiográficas, así como aspectos del procedimiento (incluídos los estudios de OCT) entre ambos grupos. Resultados: No se encontraron diferencias clínicas o angiográficas estadísticamente significativas entre ambos grupos. La indicación más frecuente de revascularización coronaria fué la presencia de angina de esfuerzo (60% vs. 70% p = 0.45), sin incluirse casos de IAMCEST. La arteria descendente anterior fué el principal vaso diana, con un diámetro medio de 3.46 ± 0.23 mm en el grupo de Absorb® y de 3.52 ± 0.19mm en el grupo de Magmaris® (p = 0.56). En todos los casos se realizó pre y postdilatación, con una tasa de éxito del procedimiento del 100%. Los estudios mediante OCT demostraron un mayor diámetro de stent y del vaso en el grupo de Magmaris®: 3.11 ± 0.38mm versus 3.07 ± 0.36 mm, p = 0.03 y 4.12 ± 0.51mm versus 4.04 ± 0.46mm, p = 0.04. A pesar de someter a los dispositivos Magmaris® a presiones de postdilatación ligeramente superiores (18.01 ± 2.15 vs. 17.20 ± 3.80 atm, p = 0.05), se identificó un menor porcentaje estadísticamente significativo de struts rotos o malapuestos en dicho grupo (0.15% vs. 0.27 %, p = 0.03 y 1.06 % vs. 1.46% p = 0.01). En un seguimiento a 30 días no se registraron eventos mayores: muerte cardíaca, IM relacionado con vaso diana o TLR. Conclusión: Las propiedades mecánicas del scaffold metálico bioresorbible Magmaris® permiten alcanzar mayores diámetros de stent y vaso de forma segura tras su implante, con una baja tasa de malaposición y disrupción.
Subject(s)
Absorbable Implants , Coronary Artery Disease/surgery , Drug-Eluting Stents , Tissue Scaffolds , Aged , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Female , Humans , Magnesium/chemistry , Male , Middle Aged , Polyesters/chemistry , Prosthesis Design , Retrospective Studies , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
Mg-Fe layered double hydroxide intercalated with chloride (Mg-Fe-Cl LDH) was synthetized, characterized, and evaluated as adsorbent to remove nitrate from aqueous solution. The pH, initial nitrate concentration, adsorbent dosage, and particle size were investigated. Kinetic data was best represented by pseudo-second order model indicating that the rate limiting step was chemisorption. Intraparticle diffusion model indicates that adsorption kinetic is limited by external and intraparticle diffusion. Sips model was selected, based on R2, ARE, and AIC, to adequately represent the adsorption isotherms, which permits to affirm that the adsorption occurs in heterogeneous surface, obtaining the maximum adsorption capacity of 18.17 mg.g-1 at 30 oC. Thermodynamics parameters indicate that the adsorption was spontaneous, exothermic, and with structural modification. These findings come up with Mg-Fe-Cl LDH as a suitable adsorbent for nitrate and could contribute to its removal from the water and wastewater.
Subject(s)
Chlorides/chemistry , Hydroxides/chemistry , Iron/chemistry , Magnesium/chemistry , Nitrates/chemistry , Water Pollutants, Chemical , Adsorption , Hydrogen-Ion Concentration , Kinetics , Nitrates/analysisABSTRACT
Following our previous work, where we described the interaction of calcium with the Cx26 hemichannel, we further explore the same system by atomistic molecular dynamics simulations considering a different di-cation, magnesium. Specifically, the interaction of magnesium di-cation with the previously reported calcium binding sites (ASP2, ASP117, ASP159, GLU114, GLU119, GLU120, and VAL226) was investigated to identify similarities and differences between them. In order to do so, four extensive simulations were carried out. Two of them considered a Cx26 hemichannel embedded on a POPC bilayer with one of the di-cations and a sodium-chlorine solution. For the remaining two, no di-cations were included and a sodium-chlorine or potassium-chlorine solution was considered. Potassium has a similar atomic mass to calcium, and sodium to magnesium, but they both differ in charge (1e and 2e respectively). Magnesium and calcium, even having the same charge, showed different affinity for the explored protein. From the calcium binding sites referred above, we found that the magnesium di-cations only binds strongly to the GLU114 site of one connexin. For the sodium and potassium simulations, no specific interactions with the protein were found. Altogether, these results suggest that mass and steric effects play an important role in determining cation binding to Cx26 hemichannels.
Subject(s)
Connexin 26/chemistry , Lipid Bilayers/chemistry , Magnesium/chemistry , Amino Acids/chemistry , Calcium/chemistry , Electrons , Molecular Dynamics Simulation , Phosphatidylcholines/chemistryABSTRACT
Bioactive glass (BG)-based scaffolds of 45S5 composition covered with hydroxyapatite nanoparticles loaded with Mg2+, Zn2+ and, both Mg2+ and Zn2+ ions, were developed and tested as materials for tissue engineering applications. The scaffolds were prepared by the foam replica technique and mono- and bi-metal loaded and unloaded hydroxyapatite nanoparticles (HA, Zn-HA, Mg-HA and Mg-Zn-HA) were obtained by an adaptation of the wet chemical deposition method. Coating of BG with these nanoparticles was performed by dip-coating to obtain HA-BG, Zn-HA-BG, Mg-HA-BG and Mg-Zn-HA-BG scaffolds. As predictor of the bone bonding ability of the produced scaffolds, in this study we investigated the formation of an apatite layer on the scaffold surfaces in the presence of simulated body fluid. The cytotoxicity and osteogenic properties of the materials in vitro was evaluated using human osteoblast-like MG-63 cell cultures. The mineralization assay following Kokubo's protocol indicated that bi-metal loaded Mg-Zn-HA-BG scaffolds exhibited higher/faster bioactivity than mono-metal loaded scaffolds while mineralization of HA-BG, Zn-HA-BG and Mg-HA-BG was similar to that of uncoated scaffolds. Moreover, an increase of proliferation of MG-63 cells after 48â¯h and 7 days was measured by BrdU assays for Mg-Zn-HA-BG scaffolds. In agreement with these results, SEM images confirmed increased interaction between these scaffolds and cells, in comparison to that observed for mono-metal-loaded HA-coated scaffolds. Altogether, the obtained results suggest that nanocrystalline Mg-Zn-HA coatings enhance the biological performance of standard scaffolds of 45S5 BG composition. Thus these novel ion doped HA coated scaffolds are attractive systems for bone tissue engineering.
Subject(s)
Ceramics/chemistry , Coated Materials, Biocompatible/chemistry , Durapatite/chemistry , Glass/chemistry , Magnesium/chemistry , Osteoblasts/drug effects , Tissue Scaffolds , Zinc/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Body Fluids/chemistry , Cell Adhesion/drug effects , Cell Line , Cell Proliferation/drug effects , Ceramics/pharmacology , Coated Materials, Biocompatible/pharmacology , Durapatite/pharmacology , Humans , Nanoparticles/chemistry , Osteoblasts/cytology , Osteoblasts/physiology , Osteogenesis/drug effects , Tissue Engineering/methodsABSTRACT
Aim:Proteus mirabilis biofilms colonize medical devices, and their role in microbial pathogenesis is well established. Magnesium-doped zinc oxide nanoparticles (ZnO:MgO NPs) have potential antimicrobial properties; thus, we aimed at evaluating the antibiofilm activity of ZnO:MgO NPs against P. mirabilis biofilm. Materials & methods: After synthesis and characterization of ZnO:MgO NPs and their addition to a polymer film, we evaluated the stages of P. mirabilis biofilm development over glass coverslip covered by different concentrations of ZnO:MgO NPs. Results: Low concentrations of ZnO:MgO NPs affect the development of P. mirabilis biofilm. Descriptors showed reduced values in bacterial number, bacterial volume and extracellular material. Conclusion: Our results highlight this new application of ZnO:MgO NPs as a potential antibiofilm strategy in medical devices.
Subject(s)
Biofilms/drug effects , Magnesium/chemistry , Nanoparticles/chemistry , Proteus mirabilis/drug effects , Proteus mirabilis/growth & development , Zinc Oxide/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , Zinc Oxide/pharmacologyABSTRACT
Prosopis strombulifera (Lam.) Benth. is a halophytic shrub found in highly saline soils in Argentina, with high tolerance against NaCl but strong growth inhibition by Na2SO4. In the present study, the differences in the physiological responses caused by these salts and an iso-osmotic combination thereof on photosynthesis, mineral composition and metabolism were analyzed. Na2SO4 treated plants were the most affected by salinity, showing a significant decrease in several photosynthetic parameters. Proline and cysteine accumulated significantly in the plants in response to salt stress. These results show by the first time that the SO42- anion is triggering damage in the photosynthetic apparatus and consequently affecting the photosynthetic process, which may explain the strong growth inhibition in these plants at high salinity. Moreover, the SO42- anion provoke challenges in the incorporation of nutrients, decreasing the levels of K, Ca, P and Mg, and inducing a strong antioxidant activity in P. strombulifera.