RESUMO
OBJECTIVE: To uncover the involvement of long non-coding RNA (lncRNA) MALAT1 in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs), and the underlying mechanism. MATERIALS AND METHODS: Relative levels of MALAT1, microRNA-124-3p (miRNA-124-3p) and peroxisome proliferator-activated receptor alpha (PPARα) in VSMCs treated with different doses of oxidized low-density lipoprotein (ox-LDL) for different time points were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Proliferative and apoptotic changes of VSMCs overexpressing MALAT1 were assessed. Subcellular distribution of MALAT1 was analyzed. The potential binding among MALAT1, miRNA-124-3p and PPARα was determined by dual-luciferase reporter gene assay, and their interaction was determined as well. Finally, the influences of MALAT1/miRNA-124-3p/PPARα regulatory loop on the proliferative and apoptotic abilities of VSMCs were examined. RESULTS: MALAT1 and PPARα were dose-dependently downregulated in ox-LDL-treated VSMCs, whereas miRNA-124-3p was gradually upregulated. Overexpression of MALAT1 attenuated viability and induced apoptosis in ox-LDL-treated VSMCs. Moreover, MALAT1 was mainly distributed in the nucleus. Dual-luciferase reporter gene assay verified that MALAT1 could sponge miRNA-124-3p, and moreover, PPARα was the direct target of miRNA-124-3p. MALAT1 negatively regulated miRNA-124-3p level and miRNA-124-3p negatively regulated PPARα level as well. Finally, MALAT1/miRNA-124-3p/PPARα regulatory loop was identified to regulate the viability and apoptosis of ox-LDL-treated VSMCs. CONCLUSIONS: LncRNA MALAT1 mediates proliferation and apoptosis of VSMCs by sponging miRNA-124-3p to positively regulate PPARα level.
Assuntos
MicroRNAs/genética , Músculo Liso Vascular/citologia , PPAR alfa/genética , PPAR alfa/metabolismo , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas , Apoptose , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo , Humanos , Lipoproteínas LDL/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismoRESUMO
The fundamental parameters of the superconducting state such as coherence length and pairing strength are essential for understanding the nature of superconductivity. These parameters can be estimated by measuring critical parameters such as upper critical field, Hc2. In this work, Hc2 of a superconducting (110) LaAlO3/SrTiO3 interface is determined through magnetoresistive measurements as a function of the gate voltage, VG. When VG increases, the critical temperature has a dome-like shape, while Hc2 monotonically decreases. This relationship of independence between the variation of Tc and of Hc2 suggests that the Cooper pairing potential is stronger in the underdoped region and the coherence length increases with the increase of VG. The result is as for high temperature superconducting cuprates and it is different than for conventional low temperature superconductors.
Assuntos
Angiografia Digital , Artéria Basilar/anormalidades , Artéria Basilar/diagnóstico por imagem , Artéria Carótida Interna/anormalidades , Artéria Carótida Interna/diagnóstico por imagem , Angiografia Cerebral , Materiais Revestidos Biocompatíveis , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/terapia , Stents , Tomografia Computadorizada por Raios X , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/terapia , Idoso , Feminino , Seguimentos , Humanos , Resultado do TratamentoRESUMO
Fourier series and an energy mapping method were used in this study to design a lens that produces a light pattern of multiple concentric circles (LPMCC) for a light-emitting diode (LED) fishing lamp. Fourier series were used to represent the light intensity distribution curve (LIDC) of the LPMCC light pattern. Energy mapping involves performing angular energy mapping based on the LIDCs of an LED light source and LPMCC to design a freeform lens. Type I and Type II LPMCC lenses were designed according to the phototaxis behavior of fish to create a LPMCC light pattern of interleaving light-dark zones that attracts fish shoals to stay in an area for a long period. The experimental results indicated that, in comparing the LIDCs of the Type I and II lenses with the respective simulation values, the normalized cross-correlation (NCC) value reached 96%. According to a 24-hour observation of the phototaxis of Poecilia reticulata to evaluate the effectiveness of the proposed light pattern to attract fish, when a fish shoal was habituated to a light source that emitted constant illumination light, it gradually moved away from the intense light zone and hovered around the junction of the light and dark zones. In the future, the design used in this study can be applied to LED fishing lamps to replace traditional fishing lamps.
RESUMO
In this paper, total internal reflection-refraction (TIR-R) concentration (U-TIR-R-C) lens module were designed for uniformity using the energy configuration method to eliminate hot spots on the surface of solar cell and increase conversion efficiency. The design of most current solar concentrators emphasizes the high-power concentration of solar energy, however neglects the conversion inefficiency resulting from hot spots generated by uneven distributions of solar energy concentrated on solar cells. The energy configuration method proposed in this study employs the concept of ray tracing to uniformly distribute solar energy to solar cells through a U-TIR-R-C lens module. The U-TIR-R-C lens module adopted in this study possessed a 76-mm diameter, a 41-mm thickness, concentration ratio of 1134 Suns, 82.6% optical efficiency, and 94.7% uniformity. The experiments demonstrated that the U-TIR-R-C lens module reduced the core temperature of the solar cell from 108 °C to 69 °C and the overall temperature difference from 45 °C to 10 °C, and effectively relative increased the conversion efficiency by approximately 3.8%. Therefore, the U-TIR-R-C lens module designed can effectively concentrate a large area of sunlight onto a small solar cell, and the concentrated solar energy can be evenly distributed in the solar cell to achieve uniform irradiance and effectively eliminate hot spots.
RESUMO
This study employs a sub-module concept to develop high-brightness light-emitting diode (HB-LED) fishing light arrays to replace traditional fishing light attractors. The horizontal/vertical (H/V) plane light intensity distribution curve (LIDC) of a LED light source are mapped to assist in the design of a non-axisymmetric lens with a fish-attracting light pattern that illuminates sufficiently large areas and alternates between bright and dark. These LED fishing light attractors are capable of attracting schools of fish toward the perimeter of the luminous zone surrounding fishing boats. Three CT2 boats (10 to 20 ton capacity) were recruited to conduct a field test for 1 y on the sea off the southwestern coast of Taiwan. Field tests show that HB-LED fishing light array installed 5 m above the boat deck illuminated a sea surface of 5 × 12 m and achieved an illuminance of 2000 lx. The test results show that the HB-LED fishing light arrays increased the mean catch of the three boats by 5% to 27%. In addition, the experimental boats consumed 15% to 17% less fuel than their counterparts.
Assuntos
Desenho Assistido por Computador , Peixes , Lentes , Luz , Iluminação/instrumentação , Semicondutores , Animais , Desenho de Equipamento , Reprodutibilidade dos Testes , NaviosRESUMO
We demonstrate the spin selective coupling of the exciton state with cavity mode in a single quantum dot (QD)-micropillar cavity system. By tuning an external magnetic field, each spin polarized exciton state can be selectively coupled with the cavity mode due to the Zeeman effect. A significant enhancement of spontaneous emission rate of each spin state is achieved, giving rise to a tunable circular polarization degree from -90% to 93%. A four-level rate equation model is developed, and it agrees well with our experimental data. In addition, the coupling between photon mode and each exciton spin state is also achieved by varying temperature, demonstrating the full manipulation over the spin states in the QD-cavity system. Our results pave the way for the realization of future quantum light sources and the quantum information processing applications.
RESUMO
We report magnetic field control of the quantum chaotic dynamics of hydrogen analogues in an anisotropic solid state environment. The chaoticity of the system dynamics was quantified by means of energy level statistics. We analyzed the magnetic field dependence of the statistical distribution of the impurity energy levels and found a smooth transition between the Poisson limit and the Wigner limit, i.e., transition between regular Poisson and fully chaotic Wigner dynamics. The effect of the crystal field anisotropy on the quantum chaotic dynamics, which manifests itself in characteristic transitions between regularity and chaos for different field orientations, was demonstrated.
RESUMO
The anisotropic diamagnetic Kepler problem (ADKP) is realized experimentally by the orbital electrons of a P donor in Si under magnetic fields. The interference of electron wave packets which leads to quasi-Landau resonances (QLR) were observed. Applying the closed-orbit theory to an anisotropic solid state environment, we have identified orbits responsible for the QLR manifesting the quantum chaotic behavior in Rydberg atoms. The excellent consistency between the measured spectra and theoretical calculation provides unambiguous evidence of quantum chaotic dynamics of electrons in the ADKP.
RESUMO
Batch-fabrication of a micro-ball lens array (MBA) could not only reduce micro assembly costs but also replace conventional ball lenses or costly GRINs (Gradient Refractive Index) without compromising performance. Compared with conventional half-spherical micro-lenses, the MBA is a spherical micro-lens that can focus light in all directions, thus providing the flexibility required for optical applications. Current MBAs are made of SU-8 photoresist by an extrusion process rather than the traditional thermal reflow process. The aim of this study was to develop a new process for MBA batch-fabrication, performed at ambient temperature, by spin-coating SU-8 onto a silicon-wafer surface, which serves as an extrusion plate, and extruding it through a nozzle to form an MBA. The nozzle consists of a nozzle orifice and nozzle cavity, the former being defined and made from SU-8 photoresist using ultra-violet (UV) lithography, which results in good mechanical properties. In this paper, the fabrication of 4 x 4 MBAs with diameters ranging from 60 to 550 um is described. Optical measurements indicated a diameter variance within 3% and a maximum coupling efficiency of approximately 62% when the single mode fiber (SMF) was placed at a distance of 10 um from the MBA. The results of this study proved that MBA fabrication by the extrusion process can enhance the coupling efficiency.
RESUMO
Dried Coptidis Rizoma was extracted with boiling water. Conditioned medium was prepared by stimulating human peripheral blood mononuclear cells with Coptidis Rizoma extract (CR). The conditioned medium was then added to human leukemic U937 cells suspension for investigating the antiproliferation effect and the induction of apoptosis. Apparent DNA fragmentation and morphological changes occurred in U937 cells after incubating for 48 h to 72 h with the conditioned medium that had been prepared with 400 microg CR solids/mL. Flow cytometric analysis revealed that the percentage of apoptotic U937 cells increased in a time- and concentration-dependent manner. The upregulation of Bax expression, the downregulation of Bcl-2 and procaspase-3 expression, and the release of cytochrome c from the mitochondria in U937 cells were all observed. Reverse transcription-polymerase chain reaction detected cytokine-related mRNA expressions in human mononuclear cells incubated with CR. An increase in the concentration of CR in culturing medium downregulated granulocyte macrophage colony-stimulatory factor mRNA expression while upregulated interleuken-2 mRNA expression. All the above-mentioned evidences suggest that CR induces the apoptosis of human leukemic U937 cells via the changes in cytokine profile and protein expressions in mitochondria pathway and that CR has the potential to be used in the therapy of leukemia due to its strong apoptosis-promoting effect.
Assuntos
Apoptose/efeitos dos fármacos , Coptis/química , Extratos Vegetais/farmacologia , Western Blotting , Caspase 3/metabolismo , Divisão Celular/efeitos dos fármacos , Grupo dos Citocromos c , Fragmentação do DNA , Relação Dose-Resposta a Droga , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células U937/efeitos dos fármacosRESUMO
A simple steam-assisted solid phase synthesis method was developed for synthesis of boehmite nanowires in the presence of TEAOH surfactant. The boehmite nanowires had uniform diameters (12-16 nm) and length up to 1-2 microm. The morphology of the nanostructured wires was well preserved after being converted to pure gamma-Al2O3 by thermal treatment at 600 degrees C for 5 h. The nanowires of Al2O3 exhibited excellent thermal stability by retarding the phase transformation and maintaining the wires-like nanostructure after being aged up to 1300 degrees C by preventing sintering between particles at high temperatures. The surface areas of Al2O3 nanowires could be maintained as high as 68 m2/g at 1300 degrees C while the surface areas of Al2O3 micropowder shrank to 0.89 m2/g after same thermal treatment. Both in-situ XRD and 27Al NMR results indicated that the crystal structure of gamma-Al2O3 nanowires was not transformed to alpha-Al2O3 at 1300 degrees C whereas micropowder Al2O3 was fully converted to alpha-Al2O3 at 1100 degrees C.
Assuntos
Óxido de Alumínio/química , Nanopartículas/química , Nanofios/química , Hidróxido de Alumínio/química , Cristalização , Temperatura Alta , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Nanotecnologia/métodos , Pós , Análise Espectral Raman , Temperatura , Fatores de Tempo , Difração de Raios XRESUMO
In an earlier study, we reported that nitric oxide is involved in lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate-induced malignant transformation via increases in metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression in rat glioma C6 cells, however the mechanism has remained undefined. Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate alone, induced transformation in glioma C6 cells (but not in human glioblastoma cells GBM-8401 cells) without affecting their viability. An increase in inducible nitric oxide synthase protein expression, nitric oxide production, and metalloproteinase 9 enzyme activity is identified lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-treated C6 cells, however lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate and 12-o-tetradecanoylphorbol 13-acetate (but not lipopolysaccharide) addition shows the similar inductive pattern on metalloproteinase 9 enzyme activity without affecting inducible nitric oxide synthase protein expression and nitric oxide production in GBM-8401 cells. Treatment of C6 cells with lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate increases the expression of phosphorylated extracellular regulated protein kinases and Jun N-terminal kinases, but not p38, proteins, and an addition of the extracellular regulated protein kinases inhibitor PD98059 or Jun N-terminal kinases inhibitors SP600125, but not the p38 inhibitor SB203580, significantly blocked lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced inducible nitric oxide synthase protein expression and metalloproteinase 9 enzyme activity accompanied by blocking morphological transformation in C6 cells. Among 19 structurally related flavonoids, kaempferol and wogonin exhibit significant inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced morphological transformation and colony formation, and attenuation of inducible nitric oxide synthase, phosphorylated extracellular regulated protein kinases protein expression, and metalloproteinase 9 enzyme activity was observed. 2'-OH flavone at a dose of 100 microM inhibition of lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events via apoptosis induction is identified. Furthermore, lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate, induces tumoral invasion and migration in vitro and in vivo, and those are blocked by kaempferol and wogonin addition. These data suggest that combination of lipopolysaccharide and 12-o-tetradecanoylphorbol 13-acetate promotes tumoral progression via activating metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression, which is located downstream of mitogen-activated protein kinases activation, in rat glioma cells C6. Kaempferol and wogonin exhibit effective inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events, and thus possess the potential for further development.
Assuntos
Neoplasias Encefálicas/metabolismo , Movimento Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Flavonoides/farmacologia , Glioma/metabolismo , Invasividade Neoplásica/fisiopatologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/fisiopatologia , Carcinógenos/antagonistas & inibidores , Movimento Celular/fisiologia , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides/uso terapêutico , Glioma/tratamento farmacológico , Glioma/fisiopatologia , Humanos , Quempferóis/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Ratos , Acetato de Tetradecanoilforbol/antagonistas & inibidoresRESUMO
A 34-year-old woman presented with 2-year history of a dome-shaped papule on a well-circumscribed, thickened, port-wine stain on the left side of the chin. Squeezing on the port-wine-stain plaque revealed many comedos within dilated follicular orifices. The papule was excised and submitted for histological examination. Histopathological study showed a lobular neoplasm, comprising dilated, cystic pilosebaceous structures surrounded by fibrous stroma, bearing the characteristics of folliculosebaceous cystic hamartoma. The reported case shows that, in addition to the vascular nature, both ectodermal and mesenchymal abnormalities may be involved in port-wine stains.
Assuntos
Dermatoses Faciais/patologia , Hamartoma/patologia , Mancha Vinho do Porto/patologia , Adulto , Feminino , Folículo Piloso/patologia , Humanos , Glândulas Sebáceas/patologiaRESUMO
Fusarium solani keratitis is a rare ocular infectious disease. The clinical characteristics and treatment methods of 18 patients with culture proven F. solani keratitis between July 1997 and December 2003 and with a follow-up period of more than 4 months were analysed retrospectively. The patients were divided into two groups based on the severity of keratitis. Group A (n = 13) displayed non-severe keratitis and were treated with debridement, lamellar keratectomy and antifungal medication. Group B (n = 5) displayed severe keratomycosis and were treated with lamellar keratectomy combined with amniotic membrane transplantation (AMT) and antifungal medication. In group A, wound healing did not interfere with the integrity of the anterior chamber. The mean re-epithelialisation time was 12.67 days (range: 5-21 days). All patients were free of major immediate postoperative complications. In group B, AMT preserved the anterior chamber integrity in two cases, but failed to do so in the other three cases. Therapeutic patch grafts were required in these three cases. Non-severe F. solani keratitis is best treated with superficial keratectomy. Timely AMT combined with lamellar keratectomy appears to be an adjuvant therapy for severe keratomycosis and avoiding emergent therapeutic penetrating keratoplasty. However, AMT was effective in cases involving non-suppurative Fusarium keratitis.
Assuntos
Infecções Oculares Fúngicas/terapia , Fusarium , Ceratite/terapia , Micoses/terapia , Adulto , Idoso , Âmnio/transplante , Antifúngicos/uso terapêutico , Terapia Combinada , Córnea/cirurgia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/cirurgia , Feminino , Seguimentos , Humanos , Ceratite/tratamento farmacológico , Ceratite/cirurgia , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/cirurgia , Estudos Retrospectivos , CicatrizaçãoRESUMO
Moderate basic sites could be created onto mesoporous Si-MCM-41 materials by postsynthesis modification with highly dispersed La2O3. The La2O3-modified MCM-41 materials (designated here as LaM) have been characterized by Fourier transform infrared spectroscopy, temperature-programmed desorption, X-ray photoelectron spectroscopy, X-ray diffraction (XRD), and N2 adsorption/desorption and have been tested as model adsorbents for CO2 adsorption. XRD and N2 adsorption results showed that all LaM materials still maintained their uniform hexagonal mesoporous structure even after postsynthesis modification with La2O3 loading up to 20 wt %. Although the surface area, pore size, and pore volume of LaM materials decreased with increasing La2O3 loading, their capacity for CO2 storage could be significantly improved when La2O3 loading was increased from 0 to 10 wt %. Unidentate and bidentate carbonates have been identified by in situ FTIR as the two types of CO2 species adsorbed on LaM surface. The LaM material also possesses good thermal stability, allowing the model adsorbent to be regenerated at high temperature and recyclable.
Assuntos
Dióxido de Carbono/química , Lantânio/química , Membranas Artificiais , Compostos de Organossilício/química , Óxidos/química , Silício/química , Adsorção , Tamanho da Partícula , Propriedades de Superfície , TemperaturaRESUMO
BACKGROUND: 5-aminolaevulinic acid (ALA) is used as a protoporphyrin IX-precursor for the photodynamic therapy of superficial skin cancer and cutaneous metastases of internal malignancies. However, the permeability of hydrophilic ALA across the skin is very low. OBJECTIVES AND METHODS: The objective of this study was to optimize and enhance the in vitro skin permeation of ALA by two resurfacing techniques: erbium:yttrium-aluminium-garnet (Erb:YAG) laser and microdermabrasion. Light microscopic changes in pig skin caused by these techniques were also compared. The electrically assisted methods, iontophoresis and electroporation, were also used to facilitate ALA permeation across laser- or microdermabrasion-treated skin. RESULTS: Among the modalities tested in this study the Erb:YAG laser showed the greatest enhancement of ALA permeation. The laser fluence was found to play an important role in controlling the drug flux, producing enhancement ratios from 4-fold to 246-fold relative to the control. The skin permeation of ALA across microdermabrasion-treated skin was approximately 5-15-fold higher than that across intact skin. Both the ablated effect of the stratum corneum (SC) and ALA flux were proportional to the treatment duration of microdermabrasion. The application of iontophoresis or electroporation alone also increased the ALA permeation by approximately 15-fold and 2-fold, respectively. The incorporation of iontophoresis or electroporation with the resurfacing techniques caused a profound synergistic effect on ALA permeation. CONCLUSIONS: This basic study has encouraged the further investigation of ALA permeation by laser or microdermabrasion.
Assuntos
Ácido Aminolevulínico/administração & dosagem , Dermabrasão , Terapia a Laser , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Administração Tópica , Alumínio , Animais , Eletroporação , Érbio , Iontoforese , Modelos Animais , Permeabilidade , Absorção Cutânea , Suínos , ÍtrioRESUMO
We developed a gene gun method for the transfer of human agouti signalling protein (ASP) cDNA to alter rat skin colour in vivo. Human ASP cDNA was cloned into a modified cytomegalovirus plasmid and delivered to the skin of Long-Evans rats by gene gun bombardment. Skin pigmentation, body weight and blood sugar of ASP cDNA-transfected rats were recorded against the control group, which were injected with plasmids encoding for green fluorescent protein. The treated skin showed lighter skin colour after 3 days of ASP gene transfection. This depigmentation effect was most prominent on day 14 and the skin gradually returned to its original pigmentation by day 28. Successful transfection of ASP gene in skin and hair follicles, as well as downregulation of melanocortin-1 receptor (MC1R) and tyrosinase expression upon treatment, was confirmed using immunohistochemistry and Western blot analysis. Body weight and blood sugar in the treated rats did not show statistically significant differences as compared to control groups. These observations demonstrate that gene transfer using the gene gun method can induce high cutaneous ASP production and facilitate a switch from dark to fair colour without systemic pleiotropic effects. Such a colour switch may be that ASP is acting in a paracrine fashion. In addition, this study verifies that ASP exerts its functions by acting as an independent ligand that downregulates the melanocyte MC1R and tyrosinase protein in an in vivo system. Our result offers new, interesting insights about the effect of ASP on pigmentation, providing a novel approach to study the molecular mechanisms underlying skin melanogenesis.
Assuntos
Biolística , DNA Complementar/administração & dosagem , Terapia Genética/métodos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pigmentação da Pele/genética , Proteína Agouti Sinalizadora , Animais , Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Masculino , Monofenol Mono-Oxigenase/análise , Ratos , Ratos Long-Evans , Receptor Tipo 1 de Melanocortina/análise , Pele/química , Transgenes , Tubulina (Proteína)/análiseRESUMO
Several natural flavonoids have been demonstrated to perform some beneficial biological activities, however, higher-effective concentrations and poor-absorptive efficacy in body of flavonoids blocked their practical applications. In the present study, we provided evidences to demonstrate that flavonoids rutin, quercetin, and its acetylated product quercetin pentaacetate were able to be used with nitric oxide synthase (NOS) inhibitors (N-nitro-L-arginine (NLA) or N-nitro-L-arginine methyl ester (L-NAME)) in treatment of lipopolysaccharide (LPS) induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions in a mouse macrophage cell line (RAW 264.7). The results showed that rutin, quercetin, and quercetin pentaacetate-inhibited LPS-induced NO production in a concentration-dependent manner without obvious cytotoxic effect on cells by MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide as an indicator. Decrease of NO production by flavonoids was consistent with the inhibition on LPS-induced iNOS gene expression by western blotting. However, these compounds were unable to block iNOS enzyme activity by direct and indirect measurement on iNOS enzyme activity. Quercetin pentaacetate showed the obvious inhibition on LPS-induced PGE2 production and COX-2 gene expression and the inhibition was not result of suppression on COX-2 enzyme activity. Previous study demonstrated that decrease of NO production by L-arginine analogs effectively stimulated LPS-induced iNOS gene expression, and proposed that stimulatory effects on iNOS protein by NOS inhibitors might be harmful in treating sepsis. In this study, NLA or L-NAME treatment stimulated significantly on LPS-induced iNOS (but not COX-2) protein in RAW 264.7 cells which was inhibited by these three compounds. Quercetin pentaacetate, but not quercetin and rutin, showed the strong inhibitory activity on PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS co-treated RAW 264.7 cells. These results indicated that combinatorial treatment of L-arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS-induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX-2 genes.
Assuntos
Flavonoides/farmacologia , Isoenzimas/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Animais , Western Blotting , Linhagem Celular , Ciclo-Oxigenase 2 , Dinoprostona/biossíntese , Antagonismo de Drogas , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo II , Nitroarginina/farmacologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Rutina/farmacologiaRESUMO
The influence of an erbium:YAG laser on the transdermal delivery of drugs across skin was studied in vitro. Indomethacin and nalbuphine, which have the same molecular weight, were selected as model lipophilic and hydrophilic drugs, respectively, to compare skin permeation by laser treatment. The results indicate a significant increase in the permeation of indomethacin and nalbuphine across skin pretreated with an erbium:YAG laser. The laser had a greater effect on the permeation of hydrophilic molecules which usually possess low permeability. The laser intensity and its spot size were found to play an important role in controlling transdermal delivery of drugs. Permeation of the hydrophilic drug increased following an increase of laser energy. On the other hand, a different result was observed for the lipophilic drug transported across laser-treated skin. The stratum corneum (SC) layer in skin could be partly ablated by the erbium:YAG laser. The barrier function of the SC may also be modulated by a lower intensity of the laser without affecting the viability and structure of the epidermis/dermis as determined by histological observations. However, ultrastructural alteration of the epidermis/dermis may be caused by laser treatment. Use of an erbium:YAG laser is a good method for enhancing transdermal absorption of both lipophilic and hydrophilic drugs, because it allows precise control of SC removal, and this ablation of SC can be reversible to the original normal status.