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1.
J Colloid Interface Sci ; 581(Pt A): 185-194, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771730

RESUMO

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces.

2.
Sci Adv ; 6(16): eaaz4316, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426455

RESUMO

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

3.
Colloids Surf B Biointerfaces ; 193: 111108, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32408256

RESUMO

Biomineralization of metal organic frameworks (MOFs) using biomolecules has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule encapsulation, protection and controlled release. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process. A library of biomolecules (peptides and proteins) with different charges were systematically studied to fundamentally understand the role of biomolecules and their proprieties in biomolecule-mediated MOF biomineralization. Biomolecule charge, amino acid sequence and stirring speed have been demonstrated to play important roles in controlling biomineralization reaction rate, particle shape and morphology.

4.
Heliyon ; 5(8): e02277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31440604

RESUMO

Various pesticide nanocarriers have been developed. However, their pest-control applications remain limited in laboratories. Herein, we developed silica nanocapsules encapsulating fipronil (SNC) and their engineered form, poly(ethyleneimine)-coated SNC (SNC-PEI), based on recombinant catalytic modular protein D4S2 and used them against termite colonies Coptotermes lacteus in fields. To achieve this, an integrated biomolecular bioprocess was developed to produce D4S2 for manufacturing SNC containing fipronil with high encapsulation efficiency of approximately 97% at benign reaction conditions and at scales sufficient for the field applications. PEI coating was achieved via electrostatic interactions to yield SNC-PEI with a slower release of fipronil than SNC without coating. As a proof-of-concept, bait toxicants containing varied fipronil concentrations were formulated and exposed to nine termite mounds, aiming to prolong fipronil release hence allowing sufficient time for termites to relocate the baits into and distribute throughout the colony, and to eliminate that colony. Some baits were relocated into the mounds, but colonies were not eliminated due to several reasons. We caution others interested in producing bait toxicants to be aware of the multilevel resistance mechanisms of the Coptotermes spp. "superorganism".

5.
Angew Chem Int Ed Engl ; 58(40): 14357-14364, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364258

RESUMO

A large range of nanoparticles have been developed to encapsulate hydrophobic drugs. However, drug loading is usually less than 10 % or even 1 %. Now, core-shell nanoparticles are fabricated having exceptionally high drug loading up to 65 % (drug weight/the total weight of drug-loaded nanoparticles) and high encapsulation efficiencies (>99 %) based on modular biomolecule templating. Bifunctional amphiphilic peptides are designed to not only stabilize hydrophobic drug nanoparticles but also induce biosilicification at the nanodrug particle surface thus forming drug-core silica-shell nanocomposites. This platform technology is highly versatile for encapsulating various hydrophobic cargos. Furthermore, the high drug loading nanoparticles lead to better in vitro cytotoxic effects and in vivo suppression of tumor growth, highlighting the significance of using high drug-loading nanoparticles.

6.
ACS Nano ; 13(7): 7410-7424, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31287659

RESUMO

The physicochemical properties of nanoparticles play critical roles in regulating nano-bio interactions. Whereas the effects of the size, shape, and surface charge of nanoparticles on their biological performances have been extensively investigated, the roles of nanoparticle mechanical properties in drug delivery, which have only been recognized recently, remain the least explored. This review article provides an overview of the impacts of nanoparticle mechanical properties on cancer drug delivery, including (1) basic terminologies of the mechanical properties of nanoparticles and techniques for characterizing these properties; (2) current methods for fabricating nanoparticles with tunable mechanical properties; (3) in vitro and in vivo studies that highlight key biological performances of stiff and soft nanoparticles, including blood circulation, tumor or tissue targeting, tumor penetration, and cancer cell internalization, with a special emphasis on the underlying mechanisms that control those complicated nano-bio interactions at the cellular, tissue, and organ levels. The interesting research and findings discussed in this review article will offer the research community a better understanding of how this research field evolved during the past years and provide some general guidance on how to design and explore the effects of nanoparticle mechanical properties on nano-bio interactions. These fundamental understandings, will in turn, improve our ability to design better nanoparticles for enhanced drug delivery.

7.
Adv Healthc Mater ; 8(8): e1900015, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30868753

RESUMO

Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time-consuming, and often fail to replicate human activity. Here a microfluidic tumor-on-a-chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time-elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX-loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.

8.
J Colloid Interface Sci ; 539: 497-503, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30611045

RESUMO

Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigen + adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.


Assuntos
Alginatos/síntese química , Preparações de Ação Retardada/química , Técnicas Analíticas Microfluídicas , Microesferas , Ovalbumina/química , Alginatos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Tamanho da Partícula , Propriedades de Superfície
9.
Mol Med Rep ; 19(1): 187-194, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431114

RESUMO

Various types of mesenchymal stromal cells (MSCs) have been used in urological tissue engineering but to date the existence of MSCs has not been reported in the human bladder. The present study provided evidence that a small number of MSC­like cells exist in the human bladder and designated this class of cells 'human bladder­derived MSC­like cells' (hBSCs). It was demonstrated that hBSCs can be cultured to yield a large population. These hBSCs expressed the surface markers of MSCs and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. On induction with appropriate media in vitro, hBSCs could differentiate into bladder­associated cell types, including urothelial, endothelial and smooth muscle cell­like lineages. In addition, the average telomerase activity of adult hBSCs was higher compared with adult human bone marrow­derived MSCs, but lower than that of human umbilical cord Wharton's jelly­derived MSCs. These findings may inspire future studies on the role of hBSCs in urological tissue engineering applications and in other fields.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Bexiga Urinária/citologia , Adipogenia/fisiologia , Adulto , Idoso , Linhagem da Célula/fisiologia , Células Cultivadas , Condrogênese/fisiologia , Endotélio/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/citologia , Osteogênese/fisiologia , Engenharia Tecidual/métodos , Cordão Umbilical/citologia , Urotélio/citologia
10.
ACS Nano ; 12(11): 11600-11609, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30380832

RESUMO

Nanoparticle tumor accumulation relies on a key mechanism, the enhanced permeability and retention (EPR) effect, but it remains challenging to decipher the exact impact of the EPR effect. Animal models in combination with imaging modalities are useful, but it is impossible to delineate the roles of multiple biological barriers involved in nanoparticle tumor accumulation. Here we report a microfluidic tumor-vasculature-on-a-chip (TVOC) mimicking two key biological barriers, namely, tumor leaky vasculature and 3D tumor tissue with dense extracellular matrix (ECM), to study nanoparticle extravasation through leaky vasculature and the following accumulation in tumor tissues. Intact 3D tumor vasculature was developed with selective permeability of small molecules (20 kDa) but not large ones (70 kDa). The permeability was further tuned by cytokine stimulation, demonstrating the independent control of the leaky tumor vasculature. Combined with tumor spheroids in dense ECM, our TVOC model is capable of predicting nanoparticles' in vivo tumor accumulation, thus providing a powerful platform for nanoparticle evaluation.


Assuntos
Corantes Fluorescentes/farmacocinética , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Animais , Matriz Extracelular/química , Matriz Extracelular/efeitos dos fármacos , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacos
11.
Sensors (Basel) ; 18(9)2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30217092

RESUMO

Rapid acquisition of the spatial distribution of soil nutrients holds great implications for farmland soil productivity safety, food security and agricultural management. To this end, we collected 1297 soil samples and measured the content of soil total nitrogen (TN), soil available phosphorus (AP) and soil available potassium (AK) in Zengcheng, north of the Pearl River Delta, China. Hyperspectral remote sensing images (115 bands) of the Chinese Environmental 1A satellite were used as auxiliary variables and dimensionality reduction was performed using Pearson correlation analysis and principal component analysis. The TN, AP and AK of soil were predicted in the study area based on auxiliary variables after dimensionality reduction, along with stepwise linear regression (SLR), support vector machine (SVM), random forest (RF) and back-propagation neural network (BPNN) models; 324 independent points were used to verify the predictive performance. The BPNN model, which demonstrated the best predictive accuracy among all methods, combined ordinary kriging (OK) with mapping the spatial variations of soil nutrients. Results show that the BPNN model with double hidden layers had better predictive accuracy for soil TN (root mean square error (RMSE) = 0.409 mg kg-1, R² = 44.24%), soil AP (RMSE = 40.808 mg kg-1, R² = 42.91%) and soil AK (RMSE = 67.464 mg kg-1, R² = 48.53%) compared with the SLR, SVM and RF models. The back propagation neural network-ordinary kriging (BPNNOK) model showed the best predictive results of soil TN (RMSE = 0.292 mg kg-1, R² = 68.51%), soil AP (RMSE = 29.62 mg kg-1, R² = 69.30%) and soil AK (RMSE = 49.67 mg kg-1 and R² = 70.55%), indicating the best fitting ability between hyperspectral remote sensing bands and soil nutrients. According to the spatial mapping results of the BPNNOK model, concentrations of soil TN (north-central), soil AP (central and southwest) and soil AK (central and southeast) were respectively higher in the study area. The most important bands (464⁻517 nm) for soil TN (b10, b14, b20 and b21), soil AP (b3, b19 and b22) and soil AK (b4, b11, b12 and b25) exhibited the best response and sensitivity according to the SLR, SVM, RF and BPNN models. It was concluded that the application of hyperspectral images (visible-near-infrared data) with BPNNOK model was found to be an efficient method for mapping and monitoring soil nutrients at the regional scale.

12.
EBioMedicine ; 34: 85-93, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30078736

RESUMO

BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/antagonistas & inibidores , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
13.
J Zhejiang Univ Sci B ; 19(7): 535-546, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29971992

RESUMO

Excessive forces may cause root resorption and insufficient forces would introduce no effect in orthodontics. The objective of this study was to investigate the optimal orthodontic forces on a maxillary canine, using hydrostatic stress and logarithmic strain of the periodontal ligament (PDL) as indicators. Finite element models of a maxillary canine and surrounding tissues were developed. Distal translation/tipping forces, labial translation/tipping forces, and extrusion forces ranging from 0 to 300 g (100 g=0.98 N) were applied to the canine, as well as the force moment around the canine long axis ranging from 0 to 300 g·mm. The stress/strain of the PDL was quantified by nonlinear finite element analysis, and an absolute stress range between 0.47 kPa (capillary pressure) and 12.8 kPa (80% of human systolic blood pressure) was considered to be optimal, whereas an absolute strain exceeding 0.24% (80% of peak strain during canine maximal moving velocity) was considered optimal strain. The stress/strain distributions within the PDL were acquired for various canine movements, and the optimal orthodontic forces were calculated. As a result the optimal tipping forces (40-44 g for distal-direction and 28-32 g for labial-direction) were smaller than the translation forces (130-137 g for distal-direction and 110-124 g for labial-direction). In addition, the optimal forces for labial-direction motion (110-124 g for translation and 28-32 g for tipping) were smaller than those for distal-direction motion (130-137 g for translation and 40-44 g for tipping). Compared with previous results, the force interval was smaller than before and was therefore more conducive to the guidance of clinical treatment. The finite element analysis results provide new insights into orthodontic biomechanics and could help to optimize orthodontic treatment plans.


Assuntos
Dente Canino/fisiologia , Modelos Dentários , Fenômenos Biomecânicos , Simulação por Computador , Dente Canino/anatomia & histologia , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Maxila , Fricção em Ortodontia/fisiologia , Ligamento Periodontal/fisiologia , Rotação , Estresse Mecânico , Técnicas de Movimentação Dentária/estatística & dados numéricos
14.
Eur J Pharm Biopharm ; 130: 1-10, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29908938

RESUMO

Precise engineering of nanoparticles with systematically varied properties (size, charge surface properties, targeting ligands, etc.) remains a challenge, limiting the effective optimization of nanoparticles for particular applications. Herein we report a single-step microfluidic combinatorial approach for producing a library of single and dual-ligand liposomes with systematically-varied properties including size, zeta potential, targeting ligand, ligand density, and ligand ratio. A targeting ligand folic acid and a cell penetrating peptide TAT were employed to achieve the optimal synergistic targeting effect. In 2D cell monolayer models, the single-ligand folic acid modified liposome didn't show any enhanced cellular uptake, while the incorporation of TAT peptide "switched on" the function of folic acid, and induced significant elevated cellular uptake compared to the single ligand modified liposomes, showing a strong synergistic targeting effect. The folic acid and TAT peptide dual-ligand liposome also demonstrated enhanced tumor penetration as observed using 3D tumor spheroid models. The in vivo study further confirmed the improved tumor targeting and longer tumor retention (up to 72 h) of the dual-ligand liposomes. Our work not only proved the versatility of this microfluidic combinatorial approach in producing libraries of multifunctional liposomes with controlled properties but also revealed the great potential of the optimized liposome formulation for synergistic targeting effects.


Assuntos
Ácido Fólico/administração & dosagem , Produtos do Gene tat/química , Microfluídica/métodos , Nanopartículas , Animais , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Produtos do Gene tat/administração & dosagem , Humanos , Ligantes , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Células RAW 264.7 , Fatores de Tempo
15.
Adv Healthc Mater ; 7(15): e1800106, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29797508

RESUMO

The concept of dual-ligand targeting has been around for quite some time, but remains controversial due to the intricate interplay between so many different factors such as the choice of dual ligands, their densities, ratios and length matching, etc. Herein, the synthesis of a combinatorial library of single and dual-ligand nanoparticles with systematically varied properties (ligand densities, ligand ratios, and lengths) for tumor targeting is reported. Folic acid (FA) and hyaluronic acid (HA) are used as two model targeting ligands. It is found that the length matching and ligand ratio play critical roles in achieving the synergetic effect of the dual-ligand targeting. When FA is presented on the nanoparticle surface through a 5K polyethylene glycol (PEG) chain, the dual ligand formulations using the HA with either 5K or 10K length do not show any targeting effect, but the right length of HA (7K) with a careful selection of the right ligand ratio do enhance the targeting efficiency and specificity significantly. Further in vitro 3D tumor spheroid models and in vivo xenograft mice models confirm the synergetic targeting efficiency of the optimal dual-ligand formulation (5F2H7K ). This work provides a valuable insight into the design of dual-ligand targeting nanosystems.


Assuntos
Nanopartículas/química , Animais , Feminino , Ácido Fólico/química , Humanos , Ácido Hialurônico/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis/química , Propriedades de Superfície , Ensaios Antitumorais Modelo de Xenoenxerto
16.
ACS Nano ; 12(3): 2846-2857, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29489325

RESUMO

The physicochemical properties of nanoparticles (size, charge, and surface chemistry, etc.) influence their biological functions often in complex and poorly understood ways. This complexity is compounded when the nanostructures involved have variable mechanical properties. Here, we report the synthesis of liquid-filled silica nanocapsules (SNCs, ∼ 150 nm) having a wide range of stiffness (with Young's moduli ranging from 704 kPa to 9.7 GPa). We demonstrate a complex trade-off between nanoparticle stiffness and the efficiencies of both immune evasion and passive/active tumor targeting. Soft SNCs showed 3 times less uptake by macrophages than stiff SNCs, while the uptake of PEGylated SNCs by cancer cells was independent of stiffness. In addition, the functionalization of stiff SNCs with folic acid significantly enhanced their receptor-mediated cellular uptake, whereas little improvement for the soft SNCs was conferred. Further in vivo experiments confirmed these findings and demonstrated the critical role of nanoparticle mechanical properties in regulating their interactions with biological systems.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico/metabolismo , Nanocápsulas/química , Neoplasias/metabolismo , Peptídeos/metabolismo , Dióxido de Silício/metabolismo , Animais , Linhagem Celular Tumoral , Módulo de Elasticidade , Ácido Fólico/química , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Nanocápsulas/ultraestrutura , Peptídeos/química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Dióxido de Silício/química , Propriedades de Superfície
17.
Int J Neurosci ; 128(8): 772-777, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29297712

RESUMO

OBJECTIVES: Olfactory dysfunction (ODF) has been reported in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the comparison of olfactory function and olfactory-related gray matter (GM) between patients with NMO and MS needed to be further elucidated. MATERIALS AND METHODS: Thirty-seven patients with NMO and 37 with MS were enrolled. Olfactory function was evaluated with a Japanese T&T olfactometer test kit, and the neuroanatomical features of olfactory-related GM were assessed using voxel-based morphometry. RESULTS: Olfactory deficits were found in 51.4% of patients with NMO and 40.5% of patients with MS. Patients with NMO with ODF had significantly smaller olfactory bulbs than patients with MS with ODF (p = 0.031). Olfactory-related GM atrophy was found in patients with NMO in several regions of the right orbitofrontal cortex and right superior frontal gyrus; in patients with MS, reduced GM volume was found in the right parahippocampal gyrus and piriform cortex (p < 0.05, cluster size > 200 voxels). CONCLUSIONS: Olfactory deficits are common in both NMO and MS. However, the neuroanatomical features related to olfactory deficits differ greatly between the two diseases.


Assuntos
Esclerose Múltipla/complicações , Neuromielite Óptica/complicações , Transtornos do Olfato/etiologia , Adulto , Avaliação da Deficiência , Feminino , Humanos , Japão , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Transtornos do Olfato/diagnóstico por imagem , Bulbo Olfatório/diagnóstico por imagem , Limiar Sensorial/fisiologia , Índice de Gravidade de Doença
19.
J Biomech Eng ; 139(12)2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28816344

RESUMO

The method used in biomechanical modeling for finite element method (FEM) analysis needs to deliver accurate results. There are currently two solutions used in FEM modeling for biomedical model of human bone from computerized tomography (CT) images: one is based on a triangular mesh and the other is based on the parametric surface model and is more popular in practice. The outline and modeling procedures for the two solutions are compared and analyzed. Using a mandibular bone as an example, several key modeling steps are then discussed in detail, and the FEM calculation was conducted. Numerical calculation results based on the models derived from the two methods, including stress, strain, and displacement, are compared and evaluated in relation to accuracy and validity. Moreover, a comprehensive comparison of the two solutions is listed. The parametric surface based method is more helpful when using powerful design tools in computer-aided design (CAD) software, but the triangular mesh based method is more robust and efficient.


Assuntos
Análise de Elementos Finitos , Mandíbula , Fenômenos Mecânicos , Fenômenos Biomecânicos , Imageamento Tridimensional , Mandíbula/diagnóstico por imagem , Mandíbula/fisiologia , Amplitude de Movimento Articular , Tomografia Computadorizada por Raios X
20.
Stem Cells Dev ; 26(17): 1283-1292, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28548571

RESUMO

RHO GTPases regulate cell migration, cell-cycle progression, and cell survival in response to extracellular stimuli. However, the regulatory effects of RHO GTPases in mesenchymal stromal cells (MSCs) are unclear. Herein, we show that CDC42 acts as an essential factor in regulating cell proliferation and also takes part in lipotoxic effects of palmitate in human umbilical cord Wharton's jelly derived MSCs (hWJ-MSCs). Cultured human bone marrow, adipose tissue, and hWJ-MSC derived cells had varying pro-inflammatory cytokine secretion levels and cell death rates when treated by palmitate. Strikingly, the proliferation rate of these types of MSCs correlated with their sensitivity to palmitate. A glutathione-S-transferase pull-down assay demonstrated that hWJ-MSCs had the highest activation of CDC42, which was increased by palmitate treatment in a time-dependent manner. We demonstrated that palmitate-induced synthesis of pro-inflammatory cytokines and cell death was attenuated by shRNA against CDC42. In CDC42 depleted hWJ-MSCs, population-doubling levels were notably decreased, and phosphorylation of ERK1/2 and p38 MAPK was reduced. Our data therefore suggest a mechanistic role for CDC42 activity in hWJ-MSC proliferation and identified CDC42 activity as a promising pharmacological target for ameliorating lipotoxic cell dysfunction and death.


Assuntos
Células-Tronco Mesenquimais/citologia , Palmitatos/toxicidade , Cordão Umbilical/citologia , Geleia de Wharton/citologia , Proteína cdc42 de Ligação ao GTP/metabolismo , Adulto , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade
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