Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Molecules ; 27(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35335198

RESUMO

Polyopes affinis is a red algal species commonly found on the South coast and near Jeju Island, Korea. This study aimed to determine whether P. affinis extracts can inhibit the pathogenesis of T-helper-2 (Th2)-mediated inflammation in a human keratinocyte cell line of atopic dermatitis (AD). Cells were incubated with 10 ng/mL of interferon gamma (IFN-γ) and 10 ng/mL of tumor necrosis factor-alpha (TNF-α) at various concentrations of PAB (10, 30, and 60 µg/mL) and PAA (100, 500, and 1000 µg/mL) extracts. A gene-ontology (GO)-enrichment analysis revealed that PAB significantly enriched the genes associated with biological processes such as cell adhesion, immune response, inflammation, and chemokine-mediated pathways. PAB suppressed the expression of the secretory proteins and mRNAs that are associated with the thymus and the production of activation-regulated chemokines (TARC/CCL17) and macrophage-derived chemokines (MDC/CCL22). The effect of the extract on mitogen-activated protein kinases (MAPKs) was related to its inhibition of TARC/CCL17 and MDC/CCL22 production by blocking NF-κB and STAT1 activation. These results suggest that seaweed extract may improve AD by regulating pro-inflammatory chemokines. In conclusion, we first confirmed the existence of phloroglucinol, a polyphenol formed from a precursor called phlorotannin, which is present in PAB, and this result proved the possibility of PAB being used as a treatment for AD.


Assuntos
NF-kappa B , Fator de Necrose Tumoral alfa , Regulação para Baixo , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interferon gama/metabolismo , Queratinócitos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Int J Mol Sci ; 20(3)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30695994

RESUMO

Leathesia difformis (L.) Areschoug (L. difformis) is a species of littoral brown algae of the class Phaeophyceae. Only a few studies on the apoptotic, antiviral, and antioxidant properties of L. difformis have been reported, and its inhibitory effect on melanin synthesis has not been studied. The aim of this study was to investigate the anti-melanogenic effect of L. difformis extract on α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanocytes and its mechanism of action. L. difformis was extracted using 80% ethanol (LDE) and then fractioned between ethyl acetate (LDE-EA) and water (LDE-A). Our data demonstrated that LDE-EA significantly inhibited melanin level and cellular tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of genes associated with melanin synthesis, such as microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (Dct), and melanocortin 1 receptor (Mc1r) was down-regulated by LDE-EA treatment. Moreover, LDE-EA decreased p-CREB levels, which suggests that the inhibition of the cAMP/PKA/CREB pathways may be involved in the anti-melanogenic effect of LDE-EA. Thus, this study revealed that LDE-EA is an effective inhibitor of hyperpigmentation through inhibition of CREB pathways and may be considered as a potential therapeutic agent for hyperpigmentation disorders.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Phaeophyceae/química , Transdução de Sinais , alfa-MSH/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Modelos Biológicos , Monofenol Mono-Oxigenase/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Xantofilas/análise
3.
Int J Mol Sci ; 20(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871136

RESUMO

Signal reproducibility in surface-enhanced Raman scattering (SERS) remains a challenge, limiting the scope of the quantitative applications of SERS. This drawback in quantitative SERS sensing can be overcome by incorporating internal standard chemicals between the core and shell structures of metal nanoparticles (NPs). Herein, we prepared a SERS-active core Raman labeling compound (RLC) shell material, based on Au⁻Ag NPs and assembled silica NPs (SiO2@Au@RLC@Ag NPs). Three types of RLCs were used as candidates for internal standards, including 4-mercaptobenzoic acid (4-MBA), 4-aminothiophenol (4-ATP) and 4-methylbenzenethiol (4-MBT), and their effects on the deposition of a silver shell were investigated. The formation of the Ag shell was strongly dependent on the concentration of the silver ion. The negative charge of SiO2@Au@RLCs facilitated the formation of an Ag shell. In various pH solutions, the size of the Ag NPs was larger at a low pH and smaller at a higher pH, due to a decrease in the reduction rate. The results provide a deeper understanding of features in silver deposition, to guide further research and development of a strong and reliable SERS probe based on SiO2@Au@RLC@Ag NPs.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Dióxido de Silício/química , Prata/química , Compostos de Anilina/química , Benzoatos/química , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Análise Espectral Raman/métodos , Compostos de Sulfidrila/química
4.
Am J Phys Med Rehabil ; 103(3): 208-214, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37602547

RESUMO

OBJECTIVE: The aim of the study is to assess the effects of leg length discrepancy on paraspinal muscle activity and kinematic variables during gait. DESIGN: Thirty-nine healthy participants aged 5-12 yrs performed the 10-m walk test using the surface electromyography and G-walk sensor for the following conditions: (1) non-leg length discrepancy condition (leg length discrepancy 0 cm) and (2) leg length discrepancy condition with an insole on the right leg at three different heights (leg length discrepancy 0.5 cm, 1.0 cm, and 1.5 cm). The root mean square was normalized using maximal voluntary contraction and reference voluntary contraction methods (RMS_MVC and RMS_ref) and compared between the sides. RESULTS: The mean RMS_MVC of the 12th thoracic erector spinae on the right side was significantly higher at a leg length discrepancy 0.5 cm and 1 cm. Regarding the 3rd lumbar multifidus, the mean RMS_MVC on the right side was significantly higher at a leg length discrepancy 1.5 cm. The mean RMS_ref exhibited similar patterns. Pelvic obliquity and rotation showed asymmetry at a leg length discrepancy 1.5 cm compared with a leg length discrepancy 0 cm. CONCLUSIONS: A small leg length discrepancy significantly affected the asymmetric hyperactivation of the 3rd lumbar multifidus and 12th thoracic erector spinae muscles during gait. Considering the action of these muscles, asymmetric hyperactivation might result in rotation and bending of the lumbar spine and the bending of the thoracolumbar spine.


Assuntos
Perna (Membro) , Músculos Paraespinais , Humanos , Eletromiografia , Músculos Paraespinais/fisiologia , Vértebras Lombares , Região Lombossacral , Músculo Esquelético/fisiologia
5.
Comput Struct Biotechnol J ; 20: 6360-6374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420156

RESUMO

G protein-coupled receptors (GPCRs) are promising drug targets because they play a large role in physiological processes by modulating diverse signaling pathways in the human body. The GPCR-mediated signaling pathways are regulated by four types of ligands-agonists, neutral antagonists, partial agonists, and inverse agonists. Once each type of ligand is bound to the binding site, it activates, deactivates, or does not perturb signaling by shifting the conformational ensemble of GPCRs. Predicting the ligand's effect on the conformation at the binding moment could be a powerful screening tool for rational GPCR drug design. Here, we detected conformational differences by capturing the spatiotemporal residue pair pattern of the ligand-bound ß2-adrenergic receptor (ß2AR) using a 3-dimensional residual network, 3D-ResNets. The network was trained with the time series of protein distance maps extracted from hundreds of molecular dynamics (MD) simulation trajectories of ten ß2AR-ligand complexes. The MD system was constructed with a lipid bilayer embedded in an inactive ß2AR X-ray crystal structure and solvated with explicit water molecules. To train the network, three hyperparameters were tested, and it was found that the number of MD trajectories in the training set significantly affected the model's accuracy. The classification of agonists and neutral antagonists was successful, but inverse agonists were not. Between the agonists and antagonists, different residue pair patterns were spotted on the extracellular loop segment. This result demonstrates the potential application of a 3-D neural network in GPCR drug screening, as well as an analysis tool for protein functional dynamics.

6.
Nutrients ; 12(5)2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32349358

RESUMO

Pyropia yezoensis, a red alga, is popular and harvested a lot in East Asia and is famous for its medicinal properties attributable to its bioactive compounds including amino acids (porphyra-334 and shinorine, etc.), polysaccharides, phytosterols, and pigments, but its anti-inflammatory effect and mechanism of anti-atopic dermatitis (AD) have not been elucidated. In this study, we investigate the anti-AD effect of P. yezoensis extract (PYE) on mRNA and protein levels of the pro-inflammatory chemokines, thymus, and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), in human HaCaT keratinocyte cells treated to interferon (IFN)-γ or tumor necrosis factor (TNF)-α (10 ng/mL each). The effect of the PYE on extracellular signal-regulated kinase (ERK) and other mitogen-activated protein kinases (MAPKs) was related to its suppression of TARC and MDC production by blocking NF-κB activation in HaCaT cells. Furthermore, astaxanthin and xanthophyll from P. yezoensis were identified as anti-AD candidate compounds. These results suggest that the PYE may improve AD and contained two carotenoids by regulating pro-inflammatory chemokines.


Assuntos
Quimiocina CCL17/metabolismo , Quimiocina CCL22/metabolismo , Regulação para Baixo/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interferon gama/efeitos adversos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Porphyra/química , Fator de Necrose Tumoral alfa/efeitos adversos , Anti-Inflamatórios , Dermatite Atópica/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HaCaT , Humanos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Xantofilas/isolamento & purificação , Xantofilas/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
J Mol Graph Model ; 100: 107669, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32659632

RESUMO

Acinetobacter baumannii is a gram-negative bacterium that is rapidly developing drug resistance due to the abuse of antibiotics. The emergence of multidrug-resistant A. baumannii has greatly contributed to the urgency of developing new antibiotics. Previously, we had discovered two potent inhibitors of A. baumannii ß-ketoacyl acyl carrier protein synthase III (abKAS III), YKab-4 and YKab-6, which showed potent activity against A. baumannii. In addition, we have reported the crystal structure of abKAS III. In the present study, we investigated the binding between abKAS III and its inhibitors by docking simulation. Molecular dynamics (MD) simulations were performed using docked inhibitor models to identify the hotspot residues related to inhibitor binding. The binding free energies estimated using the MD simulations suggest that residues I198 and F260 of abKAS III serve as the inhibitor binding hotspots. I198, found to be responsible for mediating hydrophobic interactions with inhibitors, had the strongest residual binding energy among all abKAS III residues. We modeled glutamine substitutions of residues I198 and F260 and estimated the relative binding energies of the I198Q and F260Q variants. The results confirmed that I198 and F260 are the key inhibitor binding residues. The roles of the key residues in inhibitor binding, i.e. F260 in the α9 helix and the I198 in the ß6ß7 loop region, were investigated using principal component analysis (PCA). PCA revealed the structural changes resulting from the abKAS III I198Q and F260Q mutations and described the essential dynamics of the α9 helix. In addition, the results suggest that the ß6ß7 loop region may act as a gate keeper for ligand binding. Hydrophobic interactions involving I198 and F260 in abKAS III appear to be essential for the binding of the inhibitors YKab-4 and YKab-6. In conclusion, this study provides valuable information for the rational design of antibiotics via the inhibition of abKAS III.


Assuntos
Acinetobacter baumannii , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Transferases (Outros Grupos de Fosfato Substituídos)
8.
Sci Rep ; 8(1): 13938, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30224683

RESUMO

In this study, we report on the fabrication of multilayered tri-functional magnetic-SERS-fluorescence nanoprobes (MF-SERS particles) containing clustered superparamagnetic Fe3O4 nanoparticles (NPs), silver NPs, and a fluorescent silica layer. The MF-SERS particles exhibited strong SERS signals from the silver NPs as well as both superparamagnetism and fluorescence. MF-SERS particles were uptaken by cells, allowing successful separation using an external magnetic field. SERS and fluorescence signals could be detected from the NP-containing cells, and CD44 antibody-conjugated MF-SERS particles selectively targeted MDA-MB-231 cells. Based on these properties, MF-SERS particles proved to be a useful nanoprobe for multiplex detection and separation of cancer cells.


Assuntos
Corantes Fluorescentes/química , Nanopartículas de Magnetita/química , Dióxido de Silício/química , Linhagem Celular Tumoral , Fluorescência , Células Hep G2 , Humanos , Receptores de Hialuronatos/metabolismo , Magnetismo/métodos , Prata/química , Análise Espectral Raman/métodos
9.
Nanomaterials (Basel) ; 7(6)2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28608835

RESUMO

We report magnetic silver nanoshells (M-AgNSs) that have both magnetic and SERS properties for SERS-based detection. The M-AgNSs are composed of hundreds of Fe3O4 nanoparticles for rapid accumulation and bumpy silver shell for sensitive SERS detection by near-infrared laser excitation. The intensity of the SERS signal from the M-AgNSs was strong enough to provide single particle-level detection. We obtained much stronger SERS signal intensity from the aggregated M-AgNSs than from the non-aggregated AgNSs. 4-Fluorothiophenol was detected at concentrations as low as 1 nM, which corresponds to 0.16 ppb. The limit of detection for tetramethylthiuram disulfide was 10 µM, which corresponds to 3 ppm. The M-AgNSs can be used to detect trace amounts of organic molecules using a portable Raman system.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA