RESUMO
A novel mesoporous magnesium-based cement (MBC) was fabricated by using the mixed powders of magnesium oxide, sodium dihydrogen phosphate, and mesoporous magnesium silicate (m-MS). The results indicate that the setting time and water absorption of the MBC increased as a function of increasing m-MS content, while compressive strength decreased. In addition, the degradability of the MBC in a solution of Tris-HCl and the ability of apatite formation on the MBC were significantly improved with the increase in m-MS content. In cell culture experiments, the results show that the attachment, proliferation, and alkaline phosphatase activity of the MC3T3-E1 cells on the MBC were significantly enhanced with the increase of the content of m-MS. It can be suggested that the MBC with good cytocompatibility could promote the proliferation and differentiation of the MC3T3-E1 cells. In short, our findings indicate that the MBC containing m-MS had promising potential as a new biocement for bone regeneration and repair applications.
Assuntos
Materiais Biocompatíveis , Compostos de Magnésio/química , Silicatos de Magnésio/química , Fosfatos/química , Adesivos Teciduais , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Proliferação de Células , Camundongos , Microscopia Eletrônica de Varredura , Espectrofotometria Infravermelho , Difração de Raios XRESUMO
The gastrointestinal (GI) tract's mucus layer serves as a critical barrier and a mediator in drug nanoparticle delivery. The mucus layer's diverse molecular structures and spatial complexity complicates the mechanistic study of the diffusion dynamics of particulate materials. In response, we developed a bi-component coarse-grained mucus model, specifically tailored for the colorectal cancer environment, that contained the two most abundant glycoproteins in GI mucus: Muc2 and Muc5AC. This model demonstrated the effects of molecular composition and concentration on mucus pore size, a key determinant in the permeability of nanoparticles. Using this computational model, we investigated the diffusion rate of polyethylene glycol (PEG) coated nanoparticles, a widely used muco-penetrating nanoparticle. We validated our model with experimentally characterized mucus pore sizes and the diffusional coefficients of PEG-coated nanoparticles in the mucus collected from cultured human colorectal goblet cells. Machine learning fingerprints were then employed to provide a mechanistic understanding of nanoparticle diffusional behavior. We found that larger nanoparticles tended to be trapped in mucus over longer durations but exhibited more ballistic diffusion over shorter time spans. Through these discoveries, our model provides a promising platform to study pharmacokinetics in the GI mucus layer.
Assuntos
Muco , Nanopartículas , Polietilenoglicóis , Humanos , Nanopartículas/química , Difusão , Polietilenoglicóis/química , Muco/metabolismo , Muco/química , Mucina-2/metabolismo , Mucina-2/química , Mucina-5AC/metabolismo , Mucina-5AC/química , Mucosa Intestinal/metabolismo , Trato Gastrointestinal/metabolismo , Células Caliciformes/metabolismo , Modelos BiológicosRESUMO
We aim to assess the effects of different air pollutants on meibomian gland dysfunction (MGD). As a prospective multicenter study, 864 patients were recruited from four different regions (i.e., coal, oil, steel, and living). The oil region had a significantly lower temperature and higher O3 and SO2 concentrations than other regions. Notably, participants in oil region presented with more frequent and serious MGD signs and higher cytokine levels (median interleukin 6 [IL-6] in oil: 2.66, steel: 0.96, coal: 0.38, living: 0.56; IL-8 in oil: 117.52, steel: 46.94, coal: 26.89, living: 33; vascular endothelial growth factor [VEGF] in oil: 25.09, steel: 14.02, coal: 14.02, living: 28.47). The short-term fluctuations of cytokine levels were associated with the changes in gas levels (PM2.5 and IL-8: ß = 0.016 [0.004-0.029]; O3 and IL-6: ß = 0.576 [0.386-0.702]; O3 and IL-8: ß = 0.479 [0.369-0.890]; SO2 and VEGF: ß = 0.021 [0.001-0.047]). After long-term exposure, lid margin neovascularization (r = 0.402), meibomian gland (MG) expression (r = 0.377), MG secretion (r = 0.303), MG loss (r = 0.404), and tear meniscus height (r = - 0.345) were moderately correlated with air quality index (AQI). Individuals in oil region had more serious MGD signs and higher cytokine levels. MGD is susceptible to long-term exposure to high AQI.
Assuntos
Poluição do Ar , Doenças Palpebrais , Disfunção da Glândula Tarsal , Poluição do Ar/efeitos adversos , Carvão Mineral , Citocinas/metabolismo , Doenças Palpebrais/induzido quimicamente , Doenças Palpebrais/diagnóstico , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Estudos Prospectivos , Aço , Lágrimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Up to now, experimental limitations have prevented researchers from achieving the molecular-level understanding for the initial steps of the enzymatic hydrolysis of cellulose, where cellulase breaks down the crystal structure on the surface region of cellulose and exposes cellulose chains for the subsequent hydrolysis by cellulase. Because one of these non-hydrolytic enzymatic steps could be the rate-limiting step for the entire enzymatic hydrolysis of crystalline cellulose by cellulase, being able to analyze and understand these steps is instrumental in uncovering novel leads for improving the efficiency of cellulase. In this communication, we report an innovative application of the microcantilever technique for a real-time assessment of the morphological change of cellulose induced by a treatment of sodium chloride. This sensitive nanomechanical approach to define changes in surface structure of cellulose has the potential to permit a real-time assessment of the effect of the non-hydrolytic activities of cellulase on cellulose and thereby to provide a comprehensive understanding of the initial steps of the enzymatic hydrolysis of cellulose.
Assuntos
Celulose/química , Sistemas Microeletromecânicos/instrumentação , Nanotecnologia/instrumentação , Transdutores , Sistemas Computacionais , Desenho de Equipamento , Análise de Falha de Equipamento , Conformação MolecularRESUMO
The nano drug delivery system (NDDS) has been extensively investigated for cancer treatment because of its ability to enhance drug efficacy. However, there are only a few studies attempting NDDS for AZD9291 (Osimertinib). Here, we encapsulated AZD9291 in chitooligosaccharides (COS)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles. COS, a cationic polymer, was used to develop positively charged nanoparticles with good biological affinity. The prepared AZD-PLGA-COS NPs exhibited a smaller particle size (176.6 ± 0.4 nm), a positively charged surface (+18.65 ± 0.38 mV), and an increased cellular uptake. The IC50 of H1975 cells was reduced by 45.90%, and the expression of p-EGFR, PARP, Bak, caspase-9, Bax, and Bcl-2 was regulated to promote cellular apoptosis. Furthermore, COS was found to inhibit the expression of immune checkpoint PD-L1. This study suggests that COS-modified PLGA nanoparticles with low toxicity and high encapsulation efficiency (EE) could potentially enhance drug efficacy.
Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quitina/análogos & derivados , Portadores de Fármacos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antígeno B7-H1/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitina/química , Quitosana , Liberação Controlada de Fármacos , Receptores ErbB/metabolismo , Humanos , Concentração Inibidora 50 , Microscopia Eletrônica de Transmissão , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Oligossacarídeos , Tamanho da Partícula , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the properties of PEEK. By adding nanoparticles, fibers, etc., elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1â¯wt% to 9â¯wt%). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vitro and in vivo, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants.
Assuntos
Cetonas/farmacologia , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Tantálio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Benzofenonas , Varredura Diferencial de Calorimetria , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Colágeno/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Teste de Materiais , Camundongos , Minerais/metabolismo , Nanopartículas/toxicidade , Osseointegração/efeitos dos fármacos , Osteogênese/genética , Polímeros , Ratos Sprague-Dawley , Espectrometria por Raios X , Propriedades de Superfície , TermogravimetriaRESUMO
Research on language production has focused on the process of utterance planning and involved studying the synchronization between visual gaze and the production of sentences that refer to objects in the immediate visual environment. However, it remains unclear how the visual grouping of these objects might influence this process. To shed light on this issue, the present research examined the effects of the visual grouping of objects in a visual display on utterance planning in two experiments. Participants produced utterances of the form "The snail and the necklace are above/below/on the left/right side of the toothbrush" for objects containing these referents (e.g., a snail, a necklace and a toothbrush). These objects were grouped using classic Gestalt principles of color similarity (Experiment 1) and common region (Experiment 2) so that the induced perceptual grouping was congruent or incongruent with the required phrasal organization. The results showed that speech onset latencies were shorter in congruent than incongruent conditions. The findings therefore reveal that the congruency between the visual grouping of referents and the required phrasal organization can influence speech production. Such findings suggest that, when language is produced in a visual context, speakers make use of both visual and linguistic cues to plan utterances.
RESUMO
A bioactive composite was prepared by incorporating 40 wt% nano-hydroxyapatite (nHA) into polyetheretherketone (PEEK) through a process of compounding, injection, and molding. The mechanical and surface properties of the nHA/PEEK composite were characterized, and the in vitro osteoblast functions in the composite were investigated. The mechanical properties (elastic modulus and compressive strength) of the nHA/PEEK composite increased significantly, while the tensile strength decreased slightly as compared with PEEK. Further, the addition of nHA into PEEK increased the surface roughness and hydrophilicity of the nHA/PEEK composite. In cell tests, compared with PEEK and ultra-high-molecular-weight polyethylene, it was found that the nHA/PEEK composite could promote the functions of MC3T3-E1 cells, including cell attachment, spreading, proliferation, alkaline phosphatase activity, calcium nodule formation, and expression of osteogenic differentiation-related genes. Incorporation of nHA into PEEK greatly improved the bioperformance of PEEK. The nHA/PEEK composite might be a promising orthopedic implant material.
Assuntos
Durapatita/farmacologia , Cetonas/farmacologia , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Animais , Benzofenonas , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Durapatita/química , Interações Hidrofóbicas e Hidrofílicas , Cetonas/química , Teste de Materiais , Camundongos , Osteogênese/efeitos dos fármacos , Polietilenoglicóis/química , Polímeros , Próteses e Implantes , Propriedades de SuperfícieRESUMO
To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and testing data sets are divided into equal size in all cases except for the neck. Overall the AAR method achieves a mean accuracy of about 2 voxels in localizing non-sparse blob-like objects and most sparse tubular objects. The delineation accuracy in terms of mean false positive and negative volume fractions is 2% and 8%, respectively, for non-sparse objects, and 5% and 15%, respectively, for sparse objects. The two object groups achieve mean boundary distance relative to ground truth of 0.9 and 1.5 voxels, respectively. Some sparse objects - venous system (in the thorax on CT), inferior vena cava (in the abdomen on CT), and mandible and naso-pharynx (in neck on MRI, but not on CT) - pose challenges at all levels, leading to poor recognition and/or delineation results. The AAR method fares quite favorably when compared with methods from the recent literature for liver, kidneys, and spleen on CT images. We conclude that separation of modality-independent from dependent aspects, organization of objects in a hierarchy, encoding of object relationship information explicitly into the hierarchy, optimal threshold-based recognition learning, and fuzzy model-based IRFC are effective concepts which allowed us to demonstrate the feasibility of a general AAR system that works in different body regions on a variety of organs and on different modalities.
Assuntos
Algoritmos , Lógica Fuzzy , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Modelos Estatísticos , Reconhecimento Automatizado de Padrão/métodos , Imagem Corporal Total/métodos , Inteligência Artificial , Simulação por Computador , Humanos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodosRESUMO
HM-3, an RGD modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory. Its robust inhibitory effects on endothelial cell migration and tumour growth have been demonstrated by in vivo and in vitro activity assays. However, the drug has relatively short half-life in vivo. For the purpose of prolonging HM-3 half-life and retaining the safety and efficacy of the peptide, the study chose methoxy-polyethylene glycol-Succinimidyl Carbonate (SC-mPEG, molecular weight 20 kDa, named SC-mPEG(20k)) to specifically modify its N terminus. Compared with HM-3, the site-specific mono-PEGylated peptide PEG(20k)-HM-3 was shown the same activity in the inhibition of B16F10 tumour in vivo (the inhibitory effect of PEG(20k)-HM-3, HM-3 and Taxol were 44.35, 39.68%, respectively), while the frequency of drug-administering reduced from twice a day to once every 3 days. Its rate of in vitro degradation in serum was markedly reduced (72.78% could still be detected after 132 h). Histochemistry and immunohistochemistry analysis showed that both HM-3 and PEG(20k)-HM-3 induced large areas of continuous necrosis within tumours and significantly reduced the vessel density compared to control. It might be a breakthrough in PEG modification field to modify a small peptide with a large PEG and reach a good result.