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1.
Homeopathy ; 111(3): 164-175, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34820794

RESUMO

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.


Assuntos
Homeopatia , Lactose , Varredura Diferencial de Calorimetria , Lactose/análise , Termogravimetria , Zinco
2.
J Struct Biol ; 213(1): 107693, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33387655

RESUMO

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.


Assuntos
Minerais/química , Dióxido de Silício/química , Dente/química , Animais , Quitina/química , Compostos Férricos/química , Gastrópodes/química , Compostos de Ferro/química , Microscopia Eletrônica de Transmissão/métodos
3.
Artif Organs ; 45(10): 1208-1218, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34036603

RESUMO

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.


Assuntos
Tecido Adiposo/citologia , Cartilagem/crescimento & desenvolvimento , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Tecido Adiposo/fisiologia , Fenômenos Biomecânicos , Cartilagem/citologia , Cartilagem/ultraestrutura , Células Cultivadas , Humanos , Hipertrofia , Células-Tronco Mesenquimais/fisiologia , Microscopia Eletrônica de Transmissão , Esferoides Celulares/fisiologia , Esferoides Celulares/ultraestrutura , Células Estromais/fisiologia
4.
Artif Organs ; 44(7): E288-E299, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31950507

RESUMO

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.


Assuntos
Cartilagem/crescimento & desenvolvimento , Condrogênese/fisiologia , Células-Tronco Mesenquimais/fisiologia , Cultura Primária de Células/métodos , Engenharia Tecidual/métodos , Tecido Adiposo/citologia , Cartilagem/citologia , Cartilagem/ultraestrutura , Diferenciação Celular/fisiologia , Células Cultivadas , Colágeno Tipo X/metabolismo , Meios de Cultura Livres de Soro , Matriz Extracelular/metabolismo , Humanos , Hipertrofia , Metaloproteinase 13 da Matriz/metabolismo , Microscopia Eletrônica de Transmissão , Esferoides Celulares/fisiologia , Esferoides Celulares/ultraestrutura , Células Estromais/fisiologia
5.
Nanotechnology ; 30(34): 345102, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30965299

RESUMO

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.


Assuntos
Lipossomos/química , Nanoestruturas/química , Protetores Solares/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/química , Composição de Medicamentos , Módulo de Elasticidade , Concentração de Íons de Hidrogênio , Camundongos , Tamanho da Partícula , Células RAW 264.7 , Ratos , Reologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Fator de Proteção Solar , Protetores Solares/metabolismo , Protetores Solares/farmacologia , Raios Ultravioleta , Viscosidade
7.
Homeopathy ; 108(1): 12-23, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30290377

RESUMO

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.


Assuntos
Arsenicais/isolamento & purificação , Condutividade Elétrica , Silício/isolamento & purificação , Citocinas/isolamento & purificação , Homeopatia/métodos , Humanos , Microscopia Eletrônica de Varredura/métodos
8.
Biometals ; 30(4): 541-548, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28608290

RESUMO

The most accepted hypothesis of magnetoreception for social insects is the ferromagnetic hypothesis which assumes the presence of magnetic material as a sensor coupled to sensitive structures that transmit the geomagnetic field information to the nervous system. As magnetite is the most common magnetic material observed in living beings, it has been suggested as basic constituent of the magnetoreception system. Antennae and head have been pointed as possible magnetosensor organs in social insects as ants, bees and termites. Samples of three antenna joints: head-scape, scape-pedicel and pedicel-third segment joints were embedded in epoxi resin, ultrathin sectioned and analyzed by transmission electron microscopy. Selected area electron diffraction patterns and X-ray energy dispersive spectroscopy were obtained to identify the nanoparticle compound. Besides iron oxides, for the first time, nanoparticles containing titanium have been identified surrounded by tissue in the antennae of ants. Given their dimension and related magnetic characteristics, these nanoparticles are discussed as being part of the magnetosensor system.


Assuntos
Formigas/ultraestrutura , Antenas de Artrópodes/ultraestrutura , Nanopartículas de Magnetita/química , Percepção Espacial/fisiologia , Titânio/química , Migração Animal/fisiologia , Animais , Formigas/anatomia & histologia , Formigas/fisiologia , Antenas de Artrópodes/anatomia & histologia , Antenas de Artrópodes/fisiologia , Campos Magnéticos , Microscopia Eletrônica de Transmissão , Microtomia , Inclusão do Tecido
9.
J Phycol ; 53(3): 642-651, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28258584

RESUMO

Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. However, the relationship between the mineral phase and the organic matrix in coralline algae has not yet been thoroughly examined. The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. A nanostructured pattern was observed in L. crispatum along the cell walls. At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. The crystallites in the bulk of the cell wall had a high level of spatial organization. However, the crystals displayed cleavages in the (104) faces after ultrathin sectioning with a microtome. This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs.


Assuntos
Calcificação Fisiológica , Carbonato de Cálcio/metabolismo , Rodófitas/fisiologia , Brasil , Parede Celular/fisiologia , Parede Celular/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão
10.
Homeopathy ; 106(3): 160-170, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28844289

RESUMO

BACKGROUND: A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. METHODS: Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). RESULTS: AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800 nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68 J/g in comparison to non-dynamized lactose (LAC; p < 0.05). CONCLUSIONS: Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.


Assuntos
Análise Diferencial Térmica/métodos , Homeopatia/métodos , Lactose/análise , Zinco/análise , Humanos , Microscopia Eletrônica de Transmissão/métodos , Espectrometria por Raios X/métodos
11.
J Struct Biol ; 196(2): 164-172, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27090155

RESUMO

In this work, the crystallography of calcareous sponges (Porifera) spicules and the organization pattern of the concentric layers present in their inner structure were investigated in 10 species of the subclass Calcaronea and three species of the subclass Calcinea. Polished spicules had specific concentric patterns that varied depending on the plane in which the spicules were sectioned. A 3D model of the concentric layers was created to interpret these patterns and the biomineralization process of the triactine spicules. The morphology of the spicules was compared with the crystallographic orientation of the calcite crystals by analyzing the Kikuchi diffraction patterns using a scanning electron microscope. Triactine spicules from the subclass Calcinea had actines (rays) elongated in the 〈210〉 direction, which is perpendicular to the c-axis. The scale spicules of the hypercalcified species Murrayona phanolepis presented the c-axis perpendicular to the plane of the scale, which is in accordance with the crystallography of all other Calcinea. The triactine spicules of the calcaronean species had approximately the same crystallographic orientation with the unpaired actine elongated in the ∼[211] direction. Only one Calcaronea species, whose triactine was regular, had a different orientation. Three different crystallographic orientations were found in diactines. Spicules with different morphologies, dimensions and positions in the sponge body had similar crystallographic directions suggesting that the crystallographic orientation of spicules in calcareous sponges is conserved through evolution.


Assuntos
Matriz Extracelular/química , Poríferos/anatomia & histologia , Animais , Calcificação Fisiológica , Cristalografia , Evolução Molecular , Microscopia Eletrônica de Varredura , Filogenia
12.
Water Sci Technol ; 74(8): 1867-1875, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27789887

RESUMO

The aims of the present work were to assess the application of a chemical process to degrade a mixture of parabens and determine the influence of a natural river water matrix on toxicity. Model effluents containing either a single compound, namely methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben or p-hydroxybenzoic acid, or to mimic realistic conditions a mixture of the six compounds was used. Fenton process was applied to reduce the organic charge and toxic properties of the model effluents. The efficiency of the decontamination has been investigated using a chemical as well as a toxicological approach. The potential reduction of the effluents' toxicity after Fenton treatment was evaluated by assessing (i) Vibrio fischeri luminescence inhibition, (ii) lethal effects amongst freshwater Asian clams (Corbicula fluminea), and (iii) the impact on mammalian neuronal activity using brain slices. From the environmental point of view such a broad toxicity analysis has been performed for the first time. The results indicate that Fenton reaction is an effective method for the reduction of chemical oxygen demand of a mixture of parabens and their toxicity to V. fischeri and C. fluminea. However, no important differences were found between raw and treated samples in regard to mammalian neuronal activity.


Assuntos
Parabenos/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Aliivibrio fischeri/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Corbicula/efeitos dos fármacos , Feminino , Oxirredução , Parabenos/toxicidade , Ratos , Ratos Wistar , Poluentes Químicos da Água/toxicidade
13.
J Mater Sci Mater Med ; 26(4): 166, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25791461

RESUMO

Hydroxyapatite (HA) has been investigated as a delivery system for antimicrobial and antibacterial agents to simultaneously stimulate bone regeneration and prevent infection. Despite evidence supporting the bactericidal efficiency of these HA carriers, few studies have focused on the effect of this association on bone regeneration. In this work, we evaluated the physico-chemical properties of hydroxyapatite microspheres loaded with chlorhexidine (CHX) at two different concentrations, 0.9 and 9.1 µgCHX/cm2 HA, and characterized their effects on in vitro osteoblast viability and bone regeneration. Ultraviolet-visible spectroscopy, scanning and transmission electron microscopy associated with energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy were used to characterize the association of CHX and HA nanoparticles. The high CHX loading dose induced formation of organic CHX plate-like aggregates on the HA surface, whereas a Langmuir film was formed at the low CHX surface concentration. Quantitative evaluation of murine osteoblast viability parameters, including adhesion, mitochondrial activity and membrane integrity of cells exposed to HA/CHX extracts, revealed a cytotoxic effect for both loading concentrations. Histomorphological analysis upon implantation into the dorsal connective tissues and calvaria of rats for 7 and 42 days showed that the high CHX concentration induced the infiltration of inflammatory cells, resulting in retarded bone growth. Despite a strong decrease in in vitro cell viability, the low CHX loading dose did not impair the biocompatibility and osteoconductivity of HA during bone repair. These results indicate that high antimicrobial doses may activate a strong local inflammatory response and disrupt the long-term osteoconductive properties of CHX-HA delivery systems.


Assuntos
Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Clorexidina/administração & dosagem , Implantes de Medicamento/administração & dosagem , Osteoblastos/fisiologia , Osteogênese/fisiologia , Células 3T3 , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Substitutos Ósseos/síntese química , Cápsulas/administração & dosagem , Cápsulas/síntese química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Clorexidina/química , Terapia Combinada , Difusão , Implantes de Medicamento/química , Durapatita/administração & dosagem , Durapatita/química , Masculino , Camundongos , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Ratos , Ratos Wistar
14.
J Biomol Struct Dyn ; : 1-16, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099329

RESUMO

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.

15.
Chemosphere ; 313: 137519, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36502913

RESUMO

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.


Assuntos
Nanoestruturas , Poluentes Químicos da Água , Animais , Humanos , Peixe-Zebra/metabolismo , Durapatita/toxicidade , Durapatita/metabolismo , Materiais Biocompatíveis/toxicidade , Materiais Biocompatíveis/metabolismo , Estresse Oxidativo , Nanoestruturas/toxicidade , Embrião não Mamífero/metabolismo , Larva , Poluentes Químicos da Água/toxicidade
16.
Front Cell Dev Biol ; 9: 756616, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35178394

RESUMO

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.

17.
Antibiotics (Basel) ; 10(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205394

RESUMO

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.

18.
Microsc Res Tech ; 83(12): 1610-1622, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920955

RESUMO

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.


Assuntos
Biomimética , Colagem Dentária , Suscetibilidade à Cárie Dentária , Dentina , Adesivos Dentinários , Teste de Materiais , Microscopia Eletrônica de Transmissão
19.
Int J Biol Macromol ; 159: 1048-1061, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32407944

RESUMO

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.


Assuntos
Celulose/análogos & derivados , Nanocompostos/química , Nanopartículas/química , Amido/análogos & derivados , Vitis/química , Filmes Comestíveis , Módulo de Elasticidade , Resistência à Tração
20.
J Dent ; 90: 103211, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31622646

RESUMO

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 70 wt.% of Si-HAp particles into a 70/30 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 (α = 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.


Assuntos
Esmalte Dentário/efeitos dos fármacos , Durapatita/uso terapêutico , Hidroxiapatitas , Nanoporos , Dióxido de Silício , Fluoreto de Sódio/química , Desmineralização do Dente/prevenção & controle , Remineralização Dentária/métodos , Cárie Dentária/prevenção & controle , Durapatita/química , Humanos , Fluoreto de Sódio/uso terapêutico
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