RESUMO
The recently discovered ferroelectricity in thin-film orthorhombic HfO2, which can be directly integrated into complementary metal-oxide semiconductor technology, has become an important research target. However, the use of orthorhombic HfO2 in practical devices has been limited by undesirable mixing with the monoclinic phase, which is nonpolar and thus degrades the ferroelectric properties. Here, we demonstrate that a Si dopant significantly stabilizes the ferroelectric phase because of its unique bonding characteristics, particularly its intrinsic tendency to form strong covalent bonds with O, thereby weakening the phase boundary to stabilize the ferroelectric orthorhombic phase over the nonpolar monoclinic phase, relatively. On the basis of our theoretical predictions, we conducted transmission electron microscopy measurements and confirmed that Si substitution doping indeed induced monoclinic structural components into the orthorhombic phase, which is a strong indication of the weakened phase boundary and subsequent facilitation of the ferroelectric transition. This work thus provides an atomic-scale picture for understanding the unique role of Si in promoting the ferroelectric phase and the dopant dependence on the wake-up effect in HfO2, offering a substantial advancement toward integrating ferroelectrics into practical devices.
RESUMO
BACKGROUND: In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon. RESULTS: Gene expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4) were used as indicators of insulin resistance. Relative protein expression levels of IRS-1 and GLUT4 were augmented in the cAT-MSC CM treatment group compared to insulin resistance models, indicating beneficial effects of cAT-MSC to DM, probably by actions of secreting factors. With reference to previous studies on fibroblast growth factor-1 (FGF1), we proposed FGF1 as a key contributing factor to the mechanism of action. We added anti-FGF1 neutralizing antibody to the CM-treated insulin resistance models. As a result, significantly diminished protein levels of IRS-1 and GLUT4 were observed, supporting our assumption. Similar results were observed in glucose uptake assay. CONCLUSIONS: Accordingly, this study advocated the potential of FGF-1 from cAT-MSC CM as an alternative insulin sensitizer and discovered a signalling factor associated with the paracrine effects of cAT-MSC.
Assuntos
Tecido Adiposo/metabolismo , Fator 1 de Crescimento de Fibroblastos/metabolismo , Resistência à Insulina , Comunicação Parácrina , Adipócitos/metabolismo , Tecido Adiposo/citologia , Animais , Cães , Transportador de Glucose Tipo 4/metabolismo , Técnicas In Vitro , Proteínas Substratos do Receptor de Insulina/metabolismo , Células-Tronco MesenquimaisRESUMO
A Gram-stain-negative bacterium, designated strain CBA4601(T), was isolated from a seawater sample obtained off the coast of Jeju Island, Korea. The organism grew in the presence of 0-4% (w/v) NaCl and at 20-35 °C and pH 7.0-9.0, with optimal growth in 2% NaCl, and at 25 °C and pH 8.0. Phylogenetic trees based on 16S rRNA gene sequences showed that strain CBA4601(T) was related to the genus Ferrimonas within the class Gammaproteobacteria. 16S rRNA gene sequence similarity between strain CBA4601(T) and Ferrimonas marina A4D-4(T), the most closely related species, was 96.9%. The G+C content of the genomic DNA from strain CBA4601(T) was 54.2 mol%, and the isoprenoid quinones menaquinone 7 (MK-7), ubiquinone 7 (Q-7) and ubiquinone 8 (Q-8) were detected. The major fatty acids were C(17:1)ω8c, C(18:1)ω9c and C(16:0), and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and an unidentified ninhydrin-positive phospholipid. On the basis of this taxonomic study using a polyphasic approach, strain CBA4601(T) represents a novel species of the genus Ferrimonas, for which the name Ferrimonas pelagia sp. nov. is proposed. The type strain is CBA4601(T) (â=KACC 16695(T)â=KCTC 32029(T)â=JCM 18401(T)).
Assuntos
Gammaproteobacteria/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/análise , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificação , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/análise , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Microbiologia da ÁguaRESUMO
Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical to the advancement of nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined that flat bands exist and induce robust yet independently switchable dipoles that exhibit a distinct ferroelectricity in hafnium dioxide (HfO2). Flat polar phonon bands in HfO2 cause extreme localization of electric dipoles within its irreducible half-unit cell widths (~3 angstroms). Contrary to conventional ferroelectrics with spread dipoles, those intrinsically localized dipoles are stable against extrinsic effects such as domain walls, surface exposure, and even miniaturization down to the angstrom scale. Moreover, the subnanometer-scale dipoles are individually switchable without creating any domain-wall energy cost. This offers unexpected opportunities for ultimately dense unit cell-by-unit cell ferroelectric switching devices that are directly integrable into silicon technology.
RESUMO
Mesenchymal stem cells (MSCs) have been used in studies on treatment of various diseases, and their application to immune-mediated diseases has garnered interest. Various methods for enhancing the immunomodulation effect of human MSCs have been used; however, similar approaches for canine MSCs are relatively unexplored. Accordingly, we evaluated immunomodulatory effects and mechanisms in canine MSCs treated with TNF-α and IFN-γ. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were incubated with the conditioned media (CM) from canine MSCs for 48â¯h. Expression of RNA was assessed by quantitative reverse transcription PCR (qRT-PCR), and protein levels were assessed by western blot. Expression of inducible nitric oxide synthase (iNOS), IL-6 and IL-1ß was significantly (one-way ANOVA) decreased in LPS-stimulated RAW 264.7 cells incubated with CM from canine MSCs compared to that in LPS-stimulated RAW 264.7 cells alone. Furthermore, anti-inflammatory effects of TNF-α- and IFN-γ-primed canine MSCs were significantly increased compared with those of naïve canine MSCs. Expression of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) were likewise significantly increased in primed canine MSCs. The level of iNOS protein in LPS-stimulated RAW 264.7 cells incubated with CM from the primed canine MSCs was decreased, but it increased when the cells were treated with NS-398(PGE2 inhibitor). In conclusion, compared with naïve canine MSCs, cells primed with TNF-α and IFN-γ cause a greater reduction in release of anti-inflammatory cytokines from LPS-stimulated RAW 264.7 cells; the mechanism is upregulation of the COX-2/PGE2 pathway.
Assuntos
Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Anti-Inflamatórios , Citocinas , Cães , Humanos , Lipopolissacarídeos , Macrófagos , Óxido NítricoRESUMO
In a previous study, we isolated octaphlorethol A (OPA) from Ishige foliacea and evaluated its anti-melanogenesis activity in a murine melanoma cell line. However, the whitening effect and toxicity of OPA have not yet been examined in vivo. Therefore, in this study, we investigated the inhibitory effect of OPA on melanin synthesis and tyrosinase activity in an in vivo zebrafish model. More than 90% of subject embryos survived upon exposure to OPA concentrations below 25 micrometer, which was not significantly different from the finding in the control group. OPA markedly inhibited melanin synthesis and tyrosinase activity in a concentration-dependent manner.
Assuntos
Phaeophyceae/metabolismo , Fenóis/isolamento & purificação , Fenóis/farmacologia , Animais , Sobrevivência Celular , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Melaninas/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Fenóis/química , Peixe-ZebraRESUMO
In this study, the potent skin-whitening effects of Octaphlorethol A (OPA) isolated from Ishige foliacea was investigated through inhibitory effect of melanin synthesis and tyrosinase activity in alpha-melanocyte stimulating hormone (α-MSH) induced B16F10 melanoma cells. OPA markedly inhibited melanin synthesis and tyrosinase activity in a concentration-dependent manner. We also found that OPA decreased microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2) protein expressions. Moreover, OPA reduces p38 MAPK protein levels and activates extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinases (JNKs) protein expressions in B16F10 cells. A specific ERK inhibitor PD98059 significantly blocks OPA-inhibited melanin synthesis and tyrosinase activity, whereas a p38MAP and JNK inhibitor had no effect. These findings provide evidence demonstrating that the anti-melanogenic effect of OPA is mediated through the activation of ERK signal pathway in B16F10 cells. These results indicate that OPA has the potential to be used as a melanogenesis inhibitor in the food and cosmetics industry.
Assuntos
Regulação para Baixo/efeitos dos fármacos , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Fenóis/farmacologia , Pigmentação/efeitos dos fármacos , Preparações Clareadoras de Pele/farmacologia , alfa-MSH/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melaninas/antagonistas & inibidores , Melanócitos/enzimologia , Melanócitos/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/metabolismo , Phaeophyceae/química , Fenóis/efeitos adversos , Fenóis/antagonistas & inibidores , Fenóis/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/isolamento & purificação , alfa-MSH/metabolismoRESUMO
We investigated the radioprotective effects of a polysaccharide isolated from enzymatic extracts of Ecklonia cava (E. cava) fermented by fungi and bacteria. We identified that the aqueous extract of the Lactobacillus brevis-fermented E. cava especially showed the highest proliferation effect. In addition, the enzymatic extract prepared by enzyme-assisted extraction using Viscozyme (VLFE) significantly increased cell proliferation. Further study indicated that the polysaccharides isolated from the >30 kDa fraction of VLFE (VLFEP) significantly enhanced survival and proliferation effects in γ-ray-irradiated cells. Also, VLFEP markedly reduced the DNA damage, production of reactive oxygen species, and the percentage of Sub-G(1) DNA contents caused by γ-ray-irradiation. Moreover, VLFEP modulated the expression levels of p53, Bax, and Bcl-2 via inhibition of IκBα degradation and phosphorylation and NFκB p65 translocation into nuclei. These results demonstrate that VLFEP has radioprotective properties including the modulation of apoptosis via the inhibition of the NFκB signaling pathway.
Assuntos
Apoptose , Raios gama/efeitos adversos , Levilactobacillus brevis , Phaeophyceae/química , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Dano ao DNA , Quinase I-kappa B/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Polissacarídeos/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Protetores contra Radiação/química , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
We investigated the composition of essential oil from fingered citron (Citrus medica L. var. sarcodactylis) (FCEO) peels by GC-MS and its anti-inflammatory effects on lipopolysaccharide (LPS) - stimulated mouse macrophage (RAW 264.7) cells. Fifteen compounds, representing 98.97% of the essential oil, were tentatively identified; the main constituents were limonene (52.44%) and γ-terpinene (28.41%). FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, FCEO suppressed the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. FCEO attenuated LPS-induced nuclear factor-κB (NF-κB) activation via inhibition of inhibitor κB-α phosphorylation. Furthermore, FCEO blocked activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that FCEO inhibits LPS-stimulated inflammation by blocking the NF-κB, JNK, and ERK pathways in macrophages, and demonstrate that FCEO possesses anti-inflammatory properties.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citrus/química , Lipopolissacarídeos/farmacologia , Óleos Voláteis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular/efeitos dos fármacos , Monoterpenos Cicloexânicos , Cicloexenos/farmacologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Limoneno , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monoterpenos/farmacologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óleos de Plantas/farmacologia , Terpenos/farmacologiaRESUMO
To assess the potential therapeutic properties of trans-1,3-diphenyl-2,3-epoxypropane-1-one (DPEP), its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E(2) (PGE(2)). Additionally, DPEP suppressed the production of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. We investigated the mechanism by which DPEP inhibits NO and PGE(2) by examining the level of nuclear factor-κB (NF-κB) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signaling pathway in RAW 264.7 cells. DPEP inhibited LPS-induced phosphorylation of ERK, JNK, and p38. Furthermore, DPEP inhibited the LPS-induced phosphorylation of inhibitor κB (IκB)-α and NF-κB p50. Taken together, the results of this study demonstrate that DPEP inhibits LPS-stimulated inflammation by blocking the NF-κB and MAPK pathways in macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Compostos de Epóxi/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Propano/análogos & derivados , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/genética , Dinoprostona/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Macrófagos/metabolismo , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Propano/farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The present study was designed to evaluate the molecular mechanisms of fucoxanthin against melanoma cell lines (B16F10 cells). Fucoxanthin reduced the proliferation of B16F10 cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during the G(0)/G(1) phase and apoptosis. Fucoxanthin-induced G(0)/G(1) arrest was associated with a marked decrease in the protein expressions of phosphorylated-Rb (retinoblastoma protein), cyclin D (1 and 2) and cyclin-dependent kinase (CDK) 4 and up-regulation of the protein levels of p15(INK4B) and p27(Kip1). Fucoxanthin-induced apoptosis was accompanied with the down-regulation of the protein levels of Bcl-xL, an inhibitor of apoptosis proteins (IAPs), resulting in a sequential activation of caspase-9, caspase-3, and PARP. Furthermore, the anti-tumor effect of fucoxanthin was assessed in vivo in Balb/c mice. Intraperitoneal administration of fucoxanthin significantly inhibited the growth of tumor mass in B16F10 cells implanted mice.
Assuntos
Antineoplásicos/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Xantofilas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Tumoral/efeitos dos fármacos , Xantofilas/farmacologiaRESUMO
Chronic exposure of skin to ultraviolet (UV) B radiation induces oxidative stress, which in turn, plays a crucial role in the induction of skin aging. The search for strategies to reverse skin aging is being constantly pursued. Here, the cytoprotective effect of quercitrin (QR) on UVB-induced cell injury in HaCaT human keratinocytes and in the zebrafish was investigated. Intracellular reactive oxygen species (ROS) generated by the exposure of HaCaT cells to UVB radiation were significantly decreased after treatment with QR, and significantly so with QR at 50 µM. As a result, QR reduced UVB-induced cell death and apoptosis in HaCaT cells. QR similarly reduced UVB-induced ROS generation and cell death in live zebrafish.
Assuntos
Apoptose/efeitos dos fármacos , Quercetina/análogos & derivados , Raios Ultravioleta , Animais , Apoptose/efeitos da radiação , Linhagem Celular , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/efeitos da radiação , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
The present study was designed to evaluate the molecular mechanisms of the action of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60 human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60 cells in a dose- and time-dependent manner accompanied by the induction of apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The results showed that ACAN-induced the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP), and decreased the level of Bcl-xL, but these effects were inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may have cancer chemopreventive and therapeutic potential, due to its ability to activate the p38 MAPK-mediated signalling pathways.