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In recent years, the scientific community has worked intensively in the search and development of new drugs to suppress viral infections, such as COVID-19. In fact, a number of active compounds have been tested; however, the absence of significant structure-activity relationships hinders the production of optimized drugs. In this study, molecular modeling techniques were employed to investigate the electronic, structural and chemical reactivity properties of a set α-ketoamides whose antiviral activities have been reported in the literature, aiming to propose new promising derivatives. The local reactivity of the compounds was evaluated via condensed-to-atoms Fukui indexes and molecular electrostatic potential. Multivariate data analysis and random forests machine learning techniques were employed to correlate the antiviral properties and electronic and structural descriptors and identify relevant variables. A series of new derivatives were then proposed and evaluated via density functional theory-based calculations, and docking/molecular dynamics with the target protein of the virus. The results suggest that active derivatives present reduced reactivity towards electrophilic agents on the central core of the molecules and high reactivity on R1 ligands. Derivatives with higher predicted antiviral activities were proposed based on simple electronic descriptors, and their efficacies are reinforced by docking and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.
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Hydroxyapatite (HA) is a biomaterial widely used in biomedical applications. Many studies have shown that ionic substituents can be incorporated into HA to produce a mineral composition more similar to natural bone tissue with more favorable biological characteristics for application in bone regeneration. However, its potentially toxic effects need to be evaluated before full approval for human use. For this purpose, an embryotoxicity test was performed on zebrafish according to OECD guideline 236. Zebrafish embryos were exposed to 1 or 3 microspheres of alginate containing nanoparticles of HA and carbonate (CHA), strontium (SrHA), and zinc-substituted HA (ZnHA) from 4 to 120 h post-fertilization (hpf). Lethality and developmental endpoints were evaluated. In addition, larval behavior at 168 hpf was also analyzed to observe whether biomaterials adversely affect optomotor and avoidance responses (neurotoxicity), as well as the oxidative stress pattern through qPCR. After 120 h exposure to all microspheres with different patterns of crystallinity, porosity, nanoparticle size, surface area, and degradation behavior, there was no mortality rate greater than 20%, indicating the non-embryotoxic character of these biomaterials. All experimental groups showed positive optomotor and avoidance responses, which means that embryo exposure to the tested biomaterials had no neurotoxic effects. Furthermore, larvae exposed to one SrHA microsphere showed a better optomotor response than the control. Furthermore, the biomaterials did not change the pattern of mRNA levels of genes related to oxidative stress even after 120 hpf. The growing number of new HA-based biomaterials produced should be accompanied by increased studies to understand the biosafety of these compounds, especially in alternative models, such as zebrafish embryos. These results reinforce our hypothesis that ion-substituted HA biomaterials do not impose toxicological effects, cause development and neuromotor impairment, or increase oxidative stress in zebrafish embryos being useful for medical devices and in the process of bone regeneration.
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Nanoestructuras , Contaminantes Químicos del Agua , Animales , Humanos , Pez Cebra/metabolismo , Durapatita/toxicidad , Durapatita/metabolismo , Materiales Biocompatibles/toxicidad , Materiales Biocompatibles/metabolismo , Estrés Oxidativo , Nanoestructuras/toxicidad , Embrión no Mamífero/metabolismo , Larva , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: Recent experimental results supporting the dynamization process show modification in the characteristics of solid mixtures. OBJECTIVE: The present work aims to evaluate the physicochemical properties of metallic zinc and lactose, evidencing the interactions between all chemical components presented in dynamized solid mixtures by analytical techniques. METHODS: Mixtures of zinc and lactose (1:9 w/w) were successively triturated at the same proportion according to the Brazilian Homeopathic Pharmacopoeia, receiving the designation of 10-1 - 10-6 (1dH - 6dH). All samples were submitted to the following characterization techniques: Atomic Absorption Spectrometry (AAS), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), and Raman Spectroscopy (RS). RESULTS: AAS results detected 97.0% of zinc in the raw material, and the triturated zinc lactose system (ZnMet) presented mean values similar to those expected for the physical mixtures: i.e., 9.94%, 1.23%, and 0.11% in the three first proportions (10-1, 10-2, 10-3), respectively. SEM images showed particle size reduction due to the trituration process. The XRD assays of ZnMet 10-3 and 10-6 indicated peak changes at 12.3° and 43.26°, probably associated with modifications of inter-atomic crystalline spacing. The thermal analysis results of dynamized samples suggest modifications in the chemical interaction between zinc and lactose induced by the physical forces applied. RS experiments showed variation in vibration frequencies due to the dynamization procedure, in which marked ZnMet 10-6 spectral modifications were detected at 357, 477, 1086 and 1142 cm-1, and in the wavelength range 860-920 cm-1. CONCLUSION: These results highlight the importance of applying suitable characterization methods to improve our understanding of the properties of homeopathic solid mixtures, whereas the uses of sensitive tools evidence the influence of trituration on the crystalline properties and in the enthalpy variation of dynamized samples.
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Homeopatía , Lactosa , Rastreo Diferencial de Calorimetría , Lactosa/análisis , Termogravimetría , ZincRESUMEN
Introdução: Os cistos branquiais são tumores congênitos laterais, resultantes de defeitos de desenvolvimento embrionário que afetam os arcos branquiais.1 As anomalias congênitas cervicais são mais comumente diagnosticadas nos primeiros anos de vida. Objetivo: Informar, discutir e analisar condutas para tratamento desse tipo de cisto congênito. Método:Relato de caso e análise de dados, diagnósticos e conduta baseada na literatura referente a Cisto Branquial da 4° Fenda. Resultados:Os cistos podem se manifestar tardiamente, mas as fístulas são, quase sempre, diagnosticadas ao nascimento ou na infância.São extremamente raros, estima-se que 95% das anomalias das fendas branquiais sejam da 2ª fenda; das 5% restantes, quase todas são da 1ª ou 3ª fenda.O diagnóstico é primariamente clínico, mas a ultrassonografia pode auxiliar no diagnóstico diferencial de um cisto branquial. O tratamento das anomalias branquiais é a excisão cirúrgica. Lactente sexo feminino, 9 meses de idade em acompanhamento de cisto branquial com conduta conservadora. O surgimento da massa se deu logo ao nascimento, havendo drenagem espontânea do cisto para o esôfago alguns dias depois. Após nove meses paciente retorna devido aumento progressivo da lesão que correlacionando com exame físico, exames de imagem levaram ao diagnóstico de cisto de 4º fenda branquial. Realizada cirurgia para remoção de Cisto juntamente com retirada de lobo esquerdo da tireoide (tireoidectomia parcial). Conclusão:Após a exerese da lesão paciente evoluiu satisfatoriamente sendo encaminhado para enfermaria e posteriormente alta com acompanhamento ambulatorial com pediatra geral.
Introduction: Branchial cysts are congenital tumors, resulting from embryonic defects that affect the branchial arches. Congenital cervical abnormalities are usually diagnosed in the first years of life. Objective: To inform, discuss and analyze treatment approaches for this type of congenital cyst. Method: Case report and analysis of data, diagnoses and approaches based on the literature addressing Fourth Branchial Cleft Cysts. Results: Cysts can manifest late, but fistulas are almost always diagnosed at birth or in childhood. They are extremely rare: it is estimated that 95% of branchial cleft anomalies involve the second cleft; of the remaining 5%, almost all arise from the first and third clefts. There are about 45 cases of fourth cleft cysts reported in the literature. The diagnosis is primarily clinical, but the ultrasound can be used for the differential diagnosis of a branchial cyst. Computed tomography will show air-fluid level in the anterior portion of the neck, in front of the thyroid and trachea, which may compress the trachea, causing respiratory distress in childhood. The treatment of branchial anomalies is surgical excision. A 9-month old female patient was being followed up after conservative treatment of a cervical mass (branchial cyst). The cyst appeared immediately after birth, but there was there was spontaneous drainage of the cyst into the esophagus a few days later. After nine months, the patient returned due to a progressive increase of the lesion, which, after physical examination and imaging exams, led to the diagnosis of a fourth branchial cleft cyst. A surgical procedure was performed to remove the cyst along with the left thyroid lobe (partial thyroidectomy). Conclusion: After the excision of the lesion, the patient made a good recovery. She was then referred to the infirmary and later discharged with outpatient follow-up by a general pediatrician.
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The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match for PVA as a dressing, as it focuses on creating a physical barrier to avoid wound dehydration. When associated with extracellular components, such as the collagen matrix, the device obtained can create the desired biological conditions to act as a skin substitute. This study aimed to analyze the anti-microbiological activity and the in vitro and in vivo responses of a bilaminar device of PVA containing AgNPs associated with a membrane of collagen-hyaluronic acid (col-HA). Additionally, mesenchymal stem cells were cultured in the device to evaluate in vitro responses and in vivo immunomodulatory and healing behavior. The device morphology revealed a porous pattern that favored water retention and in vitro cell adhesion. Controlled wounds in the dorsal back of rat skins revealed a striking skin remodeling with new epidermis fulfilling all previously injured areas after 14 and 28 days. No infections or significant inflammations were observed, despite increased angiogenesis, and no fibrosis-markers were identified as compared to controls. Although few antibacterial activities were obtained, the addition of AgNPs prevented fungal growth. All results demonstrated that the combination of the components used here as a dermal device, chosen according to previous miscellany studies of low/mid-cost biomaterials, can promote skin protection avoiding infections and dehydration, minimize the typical wound inflammatory responses, and favor the cellular healing responses, features that give rise to further clinical trials of the device here developed.
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As an alternative to the classical tissue engineering approach, bottom-up tissue engineering emerges using building blocks in bioassembly technologies. Spheroids can be used as building blocks to reach a highly complex ordered tissue by their fusion (bioassembly), representing the foundation of biofabrication. In this study, we analyzed the biomechanical properties and the fusion capacity of human adipose stem/stromal cell (ASC) we spheroids during an in vitro model of hypertrophic cartilage established by our research group. Hypertrophic induced-ASC spheroids showed a statistically significant higher Young's modulus at weeks 2 (P < .001) and 3 (P < .0005) compared with non-induced. After fusion, non-induced and induced-ASC spheroids increased the contact area and decreased their pairs' total length. At weeks 3 and 5, induced-ASC spheroids did not fuse completely, and the cells migrate preferentially in the fusion contact region. Alizarin red O staining showed the highest intensity of staining in the fused induced-ASC spheroids at week 5, together with intense staining for collagen type I and osteocalcin. Transmission electron microscopy and element content analysis (X-ray Energy Dispersive Spectroscopy) revealed in the fused quartet at week 3 a crystal-like structure. Hypertrophic induction interferes with the intrinsic capacity of spheroids to fuse. The measurements of contact between spheroids during the fusion process, together with the change in viscoelastic profile to the plastic, will impact the establishment of bioassembly protocols using hypertrophic induced-ASC spheroids as building blocks in biofabrication.
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Tejido Adiposo/citología , Cartílago/crecimiento & desarrollo , Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos/métodos , Tejido Adiposo/fisiología , Fenómenos Biomecánicos , Cartílago/citología , Cartílago/ultraestructura , Células Cultivadas , Humanos , Hipertrofia , Células Madre Mesenquimatosas/fisiología , Microscopía Electrónica de Transmisión , Esferoides Celulares/fisiología , Esferoides Celulares/ultraestructura , Células del Estroma/fisiologíaRESUMEN
We report the electron microscopy-based analysis of the major lateral tooth of the limpet Colisella subrugosa during early and intermediate stages of development. We aimed to analyze the structural relationship among the needle-like crystals of the iron oxide goethite, the amorphous silica phase that forms the tooth base and occupy inter-crystalline spaces in the cusp, and the chitin fibers of the matrix. Goethite crystals followed the three dimensional organization pattern of the chitin fibers in the cusp. In the tooth base, spherical individual silica granules were found in regions where the chitin fibers cross. The spherical granules near the interface between the tooth base and the cusp (junction zone) formed an almost continuous medium that could easily be ultrathin-sectioned for further analysis. By contrast, the nearby silica-rich region localized on the other side of the junction zone contained needle-like goethite crystals immersed in the matrix and presented a conchoidal fracture. The chitin fibers from the silica granules of the tooth base were dotted or undulating in projection with a periodicity of about 6 nm when observed by high magnification transmission electron microscopy. Very thin goethite crystals were present in the base of the cusp near the junction zone surrounded by silica. On several occasions, crystals presented internal thin straight white lines parallel to the major axis, indicating a possible growth around fibers. We propose that silica and iron oxide phases mineralization may occur simultaneously at least for some period and that silica moderates the dimensions of the iron oxide crystals.
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Minerales/química , Dióxido de Silicio/química , Diente/química , Animales , Quitina/química , Compuestos Férricos/química , Gastrópodos/química , Compuestos de Hierro/química , Microscopía Electrónica de Transmisión/métodosRESUMEN
Studies have shown that maternal malnutrition, especially a low-protein diet (LPD), plays a key role in the developmental mechanisms underlying mammary cancer programming in female offspring. However, the molecular pathways associated with this higher susceptibility are still poorly understood. Thus, this study investigated the adverse effects of gestational and lactational low protein intake on gene expression of key pathways involved in mammary tumor initiation after a single dose of N-methyl-N-nitrosourea (MNU) in female offspring rats. Pregnant Sprague-Dawley rats were fed a normal-protein diet (NPD) (17% protein) or LPD (6% protein) from gestational day 1 to postnatal day (PND) 21. After weaning (PND 21), female offspring (n = 5, each diet) were euthanized for histological analysis or received NPD (n = 56 each diet). At PND 28 or 35, female offspring received a single dose of MNU (25 mg/kg body weight) (n = 28 each diet/timepoint). After 24 h, some females (n = 10 each diet/timepoint) were euthanized for histological, immunohistochemical, and molecular analyses at PDN 29 or 36. The remaining animals (n = 18 each diet/timepoint) were euthanized when tumors reached ≥2 cm or at PND 250. Besides the mammary gland development delay observed in LPD 21 and 28 groups, the gene expression profile demonstrated that maternal LPD deregulated 21 genes related to DNA repair and DNA replication pathways in the mammary gland of LPD 35 group after MNU. We further confirmed an increased γ-H2AX (DNA damage biomarker) and in ER-α immunoreactivity in mammary epithelial cells in the LPD group at PND 36. Furthermore, these early postnatal events were followed by significantly higher mammary carcinogenesis susceptibility in offspring at adulthood. Thus, the results indicate that maternal LPD influenced the programming of chemically induced mammary carcinogenesis in female offspring through increase in DNA damage and deregulation of DNA repair and DNA replication pathways. Also, Cidea upregulation gene in the LPD 35 group may suggest that maternal LPD could deregulate genes possibly leading to increased risk of mammary cancer development and/or poor prognosis. These findings increase the body of evidence of early-transcriptional mammary gland changes influenced by maternal LPD, resulting in differential response to breast tumor initiation and susceptibility and may raise discussions about lifelong prevention of breast cancer risk.
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This study compared the ultrastructure, chemical composition, and proteases activity (PA) of sound (SD) and caries-affected dentin (CAD) in the dentin hybrid layer after using an experimental bonding system containing pyromellitic dianhydride glycerol methacrylate and biomimetic analogs. The bonding system used a three step and a total-etch procedure. Polyacrylic acid (5%) and sodium trimetaphosphate (5%) were added to the primer and monocalcium phosphate monohydrate (9%), beta-tricalcium phosphate (10.5%), and calcium hydroxide (0.5%) were added to the adhesive. Transmission electron microscopy (TEM) was used to evaluate the resultant structure, particularly the adhesive-dentin and the demineralized-SD interfaces. The chemical composition was evaluated through energy-dispersive X-ray spectroscopy (EDS) and selected area electron diffraction (SAED). The PA was measured with the Coomassie Blue-G250 coloring test, and the PA data were analyzed by ANOVA. EDS identified the presence of isolated calcium phosphate nanoparticles in the demineralized region; however, the SAED analysis did not show any evidences of hydroxyapatite (HA) neoformation in SD and CAD. The biomimetic analog-based adhesive system inhibited the activities of dentin proteases immediately after treatment. Additionally, the proteolytic activity on the affected dentin resembled that of the SD. In conclusion, no HA formed in the demineralized SD and CAD although there were calcium and phosphate deposits. The experimental adhesive system inhibited dentin proteases. The present study uses a new approach to investigate the hybrid layer behavior in dentin. The experimental adhesive system was synthesized and used on sound and affected-caries dentin as the substrate to reproduce real clinical conditions.
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Biomimética , Recubrimiento Dental Adhesivo , Susceptibilidad a Caries Dentarias , Dentina , Recubrimientos Dentinarios , Ensayo de Materiales , Microscopía Electrónica de TransmisiónRESUMEN
Nanocomposite films prepared from starch (ST) in the presence of cellulose nanocrystals (CNCs) was performed using grape pomace as raw material. CNCs were obtained by acid hydrolysis and added to filmogenic solutions (1, 2, 5, 10 and 15 g/100 g of ST). Cellulose, CNCs and Nanocomposites were characterized. Amorphous non-cellulosic materials were removed from the grape pomace presented values for CrI 64% and 71% and yield 12 and 70% in Cellulose and CNCs, respectively. Nanocomposites showed smaller permeability and the addition of 5 to 15% CNCs formed more opaque films and had improved tensile strength and Young's modulus. The addition of CNCs from 5 to 15% proved to be effective in improving mechanical properties and decreasing water vapor permeability, important characteristics in food packaging materials. This study provided an effective method to obtain CNCs from the agroindustrial waste and open the way to produce high-value starch based nanocomposites.
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Celulosa/análogos & derivados , Nanocompuestos/química , Nanopartículas/química , Almidón/análogos & derivados , Vitis/química , Películas Comestibles , Módulo de Elasticidad , Resistencia a la TracciónRESUMEN
Human adipose stem/stromal cell (ASC) spheroids were used as a serum-free in vitro model to recapitulate the molecular events and extracellular matrix organization that orchestrate a hypertrophic cartilage phenotype. Induced-ASC spheroids (ø = 450 µm) showed high cell viability throughout the period of culture. The expression of collagen type X alpha 1 chain (COLXA1) and matrix metallopeptidase 13 (MMP-13) was upregulated at week 2 in induced-ASC spheroids compared with week 5 (P < .001) evaluated by quantitative real-time PCR. In accordance, secreted levels of IL-6 (P < .0001), IL-8 (P < .0001), IL-10 (P < .0001), bFGF (P < .001), VEGF (P < .0001), and RANTES (P < .0001) were the highest at week 2. Strong in situ staining for collagen type X and low staining for TSP-1 was associated with the increase of hypertrophic genes expression at week 2 in induced-ASC spheroids. Collagen type I, osteocalcin, biglycan, and tenascin C were detected at week 5 by in situ staining, in accordance with the highest expression of alkaline phosphatase (ALPL) gene and the presence of calcium deposits as evaluated by Alizarin Red O staining. Induced-ASC spheroids showed a higher force required to compression at week 2 (P < .0001). The human ASC spheroids under serum-free inducer medium and normoxic culture conditions were induced to a hypertrophic cartilage phenotype, opening a new perspective to recapitulate endochondral ossification in vivo.
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Cartílago/crecimiento & desarrollo , Condrogénesis/fisiología , Células Madre Mesenquimatosas/fisiología , Cultivo Primario de Células/métodos , Ingeniería de Tejidos/métodos , Tejido Adiposo/citología , Cartílago/citología , Cartílago/ultraestructura , Diferenciación Celular/fisiología , Células Cultivadas , Colágeno Tipo X/metabolismo , Medio de Cultivo Libre de Suero , Matriz Extracelular/metabolismo , Humanos , Hipertrofia , Metaloproteinasa 13 de la Matriz/metabolismo , Microscopía Electrónica de Transmisión , Esferoides Celulares/fisiología , Esferoides Celulares/ultraestructura , Células del Estroma/fisiologíaRESUMEN
OBJECTIVES: To synthesize and evaluate the enamel remineralizing potential of dental composites containing silanized silica-hydroxyapatite (Si-HAp) nanoporous particles charged with sodium fluoride (NaF). METHODS: Si-HAp particles were synthesized using a solid-state method. Dental composites were prepared by incorporating 70â¯wt.% of Si-HAp particles into a 70/30â¯wt.% Bis-GMA/TEGDMA organic matrix. Four dental composites were produced: SilF, Sil, F, and NT (nontreated). For SilF and F, Si-HAp particles were previously treated with 10% NaF (F). Afterwards, SilF and Sil composites had their particles silanized (Sil) with α-methacryloxypropyl-1-trimethoxysilane (α-MPS). The remineralizing potential was evaluated in caries-like enamel lesions induced byS. mutans biofilm for seven days and after pH-cycling for fifteen days using X-ray microtomography (micro-CT). Z350 was used as a commercial control for remineralizing potential evaluation Degree of conversion (DC%), flexural strength (FS), and Knoop hardness (KHN) were characterized. Data were analyzed using one-way ANOVA and Tukey's HSD post-hoc test (αâ¯=â¯0.05). RESULTS: F presented the highest enamel remineralizing potential, followed by SilF. Alternatively, Sil and NT were not capable of totally recovering the enamel mineral loss. NT showed the highest DC%, followed by Sil, F, and SilF. Sil and NT showed the highest FS when compared to SilF and F. No statistical significance in KHN was found among the composites. CONCLUSIONS: Dental composites with Si-HAp nanoporous particles charged with NaF presented a remineralizing potential for human enamel. However, this ability underwent a subtle reduction after particle silanization. CLINICAL SIGNIFICANCE: Si-HAp nanoporous particles charged with NaF may be an alternative for producing dental composites with an improved remineralizing potential for enamel affected by caries.
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Esmalte Dental/efectos de los fármacos , Durapatita/uso terapéutico , Hidroxiapatitas , Nanoporos , Dióxido de Silicio , Fluoruro de Sodio/química , Desmineralización Dental/prevención & control , Remineralización Dental/métodos , Caries Dental/prevención & control , Durapatita/química , Humanos , Fluoruro de Sodio/uso terapéuticoRESUMEN
Background: Zinc-doped hydroxyapatite has been proposed as a graft biomaterial for bone regeneration. However, the effect of zinc on osteoconductivity is still controversial, since the release and resorption of calcium, phosphorus, and zinc in graft-implanted defects have rarely been studied. Methods: Microspheres containing alginate and either non-doped carbonated hydroxyapatite (cHA) or nanocrystalline 3.2 wt% zinc-doped cHA (Zn-cHA) were implanted in critical-sized calvarial defects in Wistar rats for 1, 3, and 6 months. Histological and histomorphometric analyses were performed to evaluate the volume density of newly formed bone, residual biomaterial, and connective tissue formation. Biomaterial degradation was characterized by transmission electron microscopy (TEM) and synchrotron radiation-based X-ray microfluorescence (SR-µXRF), which enabled the elemental mapping of calcium, phosphorus, and zinc on the microsphere-implanted defects at 6 months post-implantation. Results: The bone repair was limited to regions close to the preexistent bone, whereas connective tissue occupied the major part of the defect. Moreover, no significant difference in the amount of new bone formed was found between the two microsphere groups. TEM analysis revealed the degradation of the outer microsphere surface with detachment of the nanoparticle aggregates. According to SR-µXRF, both types of microspheres released high amounts of calcium, phosphorus, and zinc, distributed throughout the defective region. The cHA microsphere surface strongly adsorbed the zinc from organic constituents of the biological fluid, and phosphorus was resorbed more quickly than calcium. In the Zn-cHA group, zinc and calcium had similar release profiles, indicating a stoichiometric dissolution of these elements and non-preferential zinc resorption. Conclusions: The nanometric size of cHA and Zn-cHA was a decisive factor in accelerating the in vivo availability of calcium and zinc. The high calcium and zinc accumulation in the defect, which was not cleared by the biological medium, played a critical role in inhibiting osteoconduction and thus impairing bone repair.
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Alginatos/química , Regeneración Ósea , Calcio/metabolismo , Durapatita/química , Microesferas , Nanopartículas/química , Zinc/química , Zinc/metabolismo , Animales , Materiales Biocompatibles/química , Disponibilidad Biológica , Regeneración Ósea/efectos de los fármacos , Carbonatos/química , Muerte Celular , Línea Celular , Supervivencia Celular , Femenino , Ratones , Nanopartículas/ultraestructura , Ratas Wistar , Cráneo/fisiología , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Vesicular nanosystems are versatile and they are able to encapsulate actives with different solubilities, such as lipophilic and hydrophilic compounds. The most well-known vesicular nanosystems are liposomes and niosomes, the last one is formed by non-ionic surfactants. In the present work, we developed photoprotective niosomes containing sunscreens (octyl methoxycinnamate, diethylamino hydroxybenzoyl hexyl benzoate and phenylbenzimidazole sulfonic acid), non-ionic surfactants, cholesterol and stearylamine (positive-charged lipid). Studies based on dynamic light scattering techniques, entrapment efficiency and morphology by transmission electron microscopy were performed to characterize the niosomes. In addition, rheology, pH, in vitro sun protection factor (SPF) efficacy and toxicity and in vivo and in vitro safety were determined for the niosome formulations F-N1 and F-N2. The mean sizes of N1 and N2 were 168 ± 5 nm and 192 ± 8 nm, respectively, and their morphologies were spherical, unilamellar and with an entrapment efficiency of more than 45% for each sunscreen. Both formulations, F-N1 and F-N2 presented characteristics of pseudoplastic non-Newtonian fluids, showing declining viscosity with increasing shear rate applied. SPF values were considered satisfactory, 34 ± 8 for formulation F-N1 and 34 ± 5 for F-N2. The formulations did not present toxicity when tested in macrophages and the pH was compatible with skin, which minimizes allergies. The in vitro safety assay showed lipophilic sunscreens greater affinity for the epidermis, since this layer contains natural lipids. In vivo safety assay suggests that the increased skin retention of N2 is directly correlated with the positive charge of stearylamine. Stable photoprotective niosomes were obtained and were shown to be promising nanostructures to be used against solar radiation.
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Liposomas/química , Nanoestructuras/química , Protectores Solares/química , Animales , Supervivencia Celular/efectos de los fármacos , Cinamatos/química , Composición de Medicamentos , Módulo de Elasticidad , Concentración de Iones de Hidrógeno , Ratones , Tamaño de la Partícula , Células RAW 264.7 , Ratas , Reología , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Factor de Protección Solar , Protectores Solares/metabolismo , Protectores Solares/farmacología , Rayos Ultravioleta , ViscosidadRESUMEN
INTRODUCTION: According to the "silica hypothesis" formulated to explain homeopathy, the information of starting materials would be transferred to cells by silica nanoparticles detached from the glassware walls by serial dilution and agitation through epitaxy. We compared the biological activity, electrical current and silicon microparticle content (by means of scanning electron microscopy/energy-dispersive X-ray spectroscopy) of high dilutions (HDs) of arsenic prepared in plastic and glass vials to investigate the role of silica in their biological effects in vitro. MATERIALS AND METHODS: Co-cultures of macrophages and yeast (Saccharomyces cerevisiae) were treated with different HDs of arsenic prepared in plastic and glass vials. Macrophage morphology, phagocytosis index, nitric oxide (NO), and cytokine production were evaluated. RESULTS: Measurable amounts of silicon microparticles were detected only in the HDs prepared in glass vials, but ultra-centrifugation eliminated them. Specific and non-specific results were observed. Non-specific pro-inflammatory effects were seen in all dilutions prepared in plastic vials, including elevation of pro-inflammatory cytokines, NO and macrophage phagocytic index. Only the 200th centesimal dilution of arsenic produced specific decrease in interleukin-6 production in macrophages, and it was independent of the vial type or the presence of microparticles of silica in the medicine samples. The nature of the vials had an impact on the electric flow in the respective fluids. CONCLUSION: The non-specific, pro-inflammatory effects might be attributed to organic residuals detached from the vials' plastic walls during manipulation. Instead, specific silica-independent effects of the homeopathic medicine can be attributed to the decrease of interleukin-6 after treatment with the 200th centesimal dilution of arsenic.
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Arsenicales/aislamiento & purificación , Conductividad Eléctrica , Silicio/aislamiento & purificación , Citocinas/aislamiento & purificación , Homeopatía/métodos , Humanos , Microscopía Electrónica de Rastreo/métodosRESUMEN
Objective: To evaluate which examination, ultrasonography or magnetic resonance imaging, is more accurate in the measurement of malignant breast tumors in the pre-surgical evaluation, according to hormonal status. Method: This is a descriptive, crosssectional study in which we compared the largest tumor-size visualized by magnetic resonance imaging and ultrasonography before excision with the largest size visualized in the anatomopathological report. The sample was divided according to hormonal status: premenopausal women, postmenopausal women who have already had hormone-replacement therapy, and postmenopausal women who have never done hormone-replacement therapy. We evaluated which of the exams had a greater correlation with the size measured by the anatomopathological report using the Pearson correlation coefficient. Results: All the 39 patients had invasive-ductal carcinoma. When the total sample was analyzed (n=39), it was observed that the correlation between the ultrasonography and the anatomopathological report (r=0.73; p<0.001) was higher than the correlation between the magnetic resonance imaging and the anatomopathological report (r=0.57; p<0.001). In the premenopausal subgroup, the correlation between the ultrasonography and the anatomopathological report (r=0.46; p=0.05) was lower than the correlation between the magnetic resonance imaging and the anatomopathological report, (r=0.56; p=0.01). In the postmenopausal subgroup, Pearson's correlation shows that ultrasonography is better at assessing tumor size than magnetic resonance imaging, regardless of hormonereplacement therapy. Conclusion: Ultrasonography is satisfactory for pre-surgical staging in invasive-ductal carcinoma, but, when available, magnetic resonance imaging may be a better indication in premenopausal patients
Objetivo: Avaliar qual exame, ultrassonografia ou ressonância magnética, é mais preciso para dimensionar tumores malignos da mama na avaliação pré-cirúrgica, de acordo com o status hormonal. Metodologia: Trata-se de um estudo descritivo e transversal, no qual comparamos o maior diâmetro do tumor visualizado pela ressonância magnética e pela ultrassonografia antes da excisão com o maior tamanho visualizado no exame anatomopatológico da peça cirúrgica. A amostra foi dividida conforme o estado hormonal: mulheres pré-menopáusicas; pós-menopáusicas que já tiveram terapia de reposição hormonal; e pós-menopáusicas sem terapia de reposição hormonal. Avaliamos qual dos exames teve maior correlação com o tamanho medido pelo laudo anatomopatológico usando o coeficiente de correlação de Pearson. Resultados: Todas as 39 pacientes apresentavam carcinoma ductal invasivo. Na amostra total (n=39), a correlação entre ultrassonografia e exame anatomopatológico (r=0,73; p<0,001) foi maior que a correlação entre ressonância magnética e exame anatomopatológico (r=0,57; p<0,001). No subgrupo pré-menopausa, a correlação entre ultrassonografia e exame anatomopatológico (r=0,46; p=0,05) foi inferior à correlação entre ressonância magnética e exame anatomopatológico (r=0,56; p=0,01). Nas pós-menopáusicas, a correlação de Pearson mostra que a ultrassonografia é melhor para avaliar o tamanho do tumor do que a ressonância magnética, independentemente da utilização de terapia de reposição hormonal. Conclusão: A ultrassonografia é satisfatória para mensuração pré-operatória do carcinoma ductal invasivo, mas quando disponível, a ressonância magnética pode estar bem indicada em pacientes pré-menopáusicas.
RESUMEN
After insertion into bone, dental implants may be subjected to tribocorrosive conditions resulting in the release of metallic ions and solid wear debris, which can induce to peri-implant inflammatory reactions accompanied by bone loss, and ultimately implant loosening. Despite the promising ability of TiO2 nanotubes (NTs) to improve osseointegration and avoid infection-related failures, the understanding of their degradation under the simultaneous action of wear and corrosion (tribocorrosion) is still very limited. This study aims, for the first time, to study the tribocorrosion behavior of bio-functionalized TiO2 NTs submitted to two-cycle sliding actions, and compare it with conventional TiO2 NTs. TiO2 NTs grown by anodization were doped with bioactive elements, namely calcium (Ca), phosphorous (P), and zinc (Zn), through reverse polarization anodization treatments. Characterization techniques such as scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and scanning transmission electron microscopy (STEM), were used to characterize the films. Tribocorrosion tests were carried out in artificial saliva (AS) by applying two cycles of reciprocating sliding actions. The open circuit potential (OCP) was monitored before, during, and after both cycles of sliding, during which the coefficient of friction (COF) was calculated. The resulting wear scars were analyzed by SEM and EDS, and wear volume measurements were performed by 2D profilometry. Finally, the mechanical features of TiO2 NTs were accessed by nanoindentation. The results show that bio-functionalized TiO2 NTs display an enhanced tribocorrosion performance, ascribed to the growth of a nano-thick oxide film at Ti/TiO2 NTs interface, which significantly increased their adhesion strength to the substrate and consequently their hardness. Furthermore, it was discovered that during tribo-electrochemical solicitations, the formation of a P-rich tribofilm takes place, which grants both electrochemical protection and resistance to mechanical wear. This study provides fundamental and new insights for the development of multifunctional TiO2 NTs with long-term biomechanical stability and improved clinical outcomes.
Asunto(s)
Materiales Biocompatibles/química , Saliva Artificial/química , Titanio/química , Corrosión , Fricción , NanotubosRESUMEN
Internalization of hydroxyapatite nanoparticles in SAOS-2 osteoblasts for 2 and 24 h was investigated in vitro using 5 and 50 µg/mL nanoparticles in culture medium. No cytotoxic effects were observed in a PrestoBlue viability assay. Focused ion beam-scanning electron microscopy and transmission electron microscopy were used to study nanoparticle trafficking inside cells and to characterize the physicochemical properties of the remodeled nanoparticles. Nanoparticles were actively internalized by cells and maintained in intracellular membrane-bound compartments. Dissolution of hydroxyapatite nanoparticles was observed inside phagolysosome in all samples. After 24 h of internalization in cell culture assays, reprecipitation of calcium phosphate minerals was observed in membrane-bound compartments in 5 and 50 µg/mL samples. Compared to the original nanoparticles, the reprecipitated calcium phosphate phase presented a different morphology, structure, and chemical composition. Two sample preparation methods were used and confirmed that reprecipitation of the calcium phosphate crystallites occurred in the intracellular environment and not during electron microscopy sample preparation. Reprecipitation of calcium phosphate prevented the release of large amounts of calcium and phosphate ions inside the cells. This phenomenon may be linked to physiological processes in the cell that control the concentration and trafficking of intracellular calcium ions, which are highly controlled by cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 428-439, 2018.
Asunto(s)
Durapatita/química , Nanopartículas/química , Osteoblastos/citología , Línea Celular , Supervivencia Celular , Humanos , Nanopartículas/ultraestructura , Espectrometría por Rayos XRESUMEN
ABSTARCT: This work explores a new class of vortex/magnetite/iron oxide nanoparticles designed for magnetic hyperthermia applications. These nanoparticles, named Vortex Iron oxide Particles (VIPs), are an alternative to the traditional Superparamagnetic Iron Oxide Nanoparticles (SPIONs), since VIPs present superior heating power while fulfilling the main requirements for biomedical applications (low cytotoxicity and nonremanent state). In addition, the present work demonstrates that the synthesized VIPs also promote an internalization and aggregation of the particles inside the cell, resulting in a highly localized hyperthermia in the presence of an alternating magnetic field. Thereby, we demonstrate a new and efficient magnetic hyperthermia strategy in which a small, but well localized, concentration of VIPs can promote an intracellular hyperthermia process.