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1.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-31480310

RESUMEN

Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.


Asunto(s)
Contaminación del Aire/prevención & control , Fulerenos/análisis , Material Particulado/toxicidad , Agua/química , Apoptosis/efectos de los fármacos , Línea Celular , Ciudades , Proteínas Filagrina , Fulerenos/química , Humanos , Inflamación/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/ultraestructura , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Solubilidad
2.
J Cardiovasc Electrophysiol ; 24(5): 573-82, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23421445

RESUMEN

INTRODUCTION: Heart failure (HF) increases the susceptibility to atrial fibrillation (AF) and is associated with altered cardiomyocyte connexin. The regional remodeling of connexin(s) may contribute to the spatiotemporal organization of AF. This study sought to investigate the regional differences in connexin(s) and fibrosis in specific atrial regions and correlate that with the electrogram properties. METHODS AND RESULTS: Biatrial electroanatomic mapping during sinus rhythm (electrogram voltage and velocity) and AF (dominant frequency, DF) was performed in 6 ventricular pacing-induced HF dogs (at 252 beats/minute for 6 weeks) and 6 controls. Atrial tissues were sampled from 7 specific sites for analysis of the connexin and fibrosis. HF caused marked atrial dilatation, and increased the induced AF duration (P < 0.001). Remodeled connexins, including a lower expression and more lateralization of both connexin40 (Cx40) and Cx43 as well as increased regional dispersion of Cx40, in the presence of diffuse enhanced atrial fibrosis, characterized the atrial substrate of the HF dogs (P < 0.01). Regional analysis showed abnormal velocity and low electrogram voltage in the areas with downregulated Cx40 and Cx43 was enhanced in the presence of marked atrial fibrosis (>30% of area, P < 0.01). During AF, lower expression of the Cx40 was associated with higher DF in areas of less and more fibrosis, respectively (R = 0.67 and 0.58, P < 0.01). CONCLUSIONS: An altered expression of connexins correlated with the electrogram properties in the existence of diffuse enhanced atrial fibrosis associated with HF. The regional remodeling of Cx40 is likely an important factor in the maintenance of AF in HF.


Asunto(s)
Fibrilación Atrial/etiología , Conexinas/análisis , Electrocardiografía , Atrios Cardíacos/química , Atrios Cardíacos/fisiopatología , Insuficiencia Cardíaca/complicaciones , Animales , Fibrilación Atrial/patología , Western Blotting , Perros , Ecocardiografía , Fibrosis , Atrios Cardíacos/patología , Procesamiento de Imagen Asistido por Computador , Masculino , Microscopía Confocal , Proteína alfa-5 de Unión Comunicante
3.
Biomolecules ; 10(4)2020 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-32231102

RESUMEN

Exposure to particulate matter (PM) has been linked to pulmonary and cardiovascular dysfunctions, as well as skin diseases, etc. PM impairs the skin barrier functions and is also involved in the initiation or exacerbation of skin inflammation, which is linked to the activation of reactive oxygen species (ROS) pathways. Fullerene is a single C60 molecule which has been reported to act as a good radical scavenger. However, its poor water solubility limits its biological applications. The glyco-modification of fullerenes increases their water solubility and anti-bacterial and anti-virus functions. However, it is still unclear whether it affects their anti-inflammatory function against PM-induced skin diseases. Hence, glycofullerenes were synthesized to investigate their effects on PM-exposed HaCaT human keratinocytes. Our results showed that glycofullerenes could reduce the rate of PM-induced apoptosis and ROS production, as well as decrease the expression of downstream mitogen-activated protein kinase and Akt pathways. Moreover, PM-induced increases in inflammatory-related signals, such as cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2, were also suppressed by glycofullerenes. Notably, our results suggested that PM-induced impairment of skin barrier proteins, such as filaggrin, involucrin, repetin, and loricrin, could be reduced by pre-treatment with glycofullerenes. The results of this study indicate that glycofullerenes could be potential candidates for treatments against PM-induced skin diseases and that they exert their protective effects via ROS scavenging, anti-inflammation, and maintenance of the expression of barrier proteins.


Asunto(s)
Dermatitis/tratamiento farmacológico , Fulerenos/química , Fulerenos/farmacología , Queratinocitos/efectos de los fármacos , Material Particulado/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular , Dermatitis/etiología , Dinoprostona/metabolismo , Dispersión Dinámica de Luz , Proteínas Filagrina , Humanos , Queratinocitos/metabolismo , Espectroscopía de Resonancia Magnética , Tamaño de la Partícula , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier
4.
Sci Rep ; 9(1): 15233, 2019 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-31645652

RESUMEN

High blood glucose in diabetic patients often causes cardiovascular diseases (CVDs) that threats to human life. Curcumin (Cur) is known as an antioxidant agent, possesses anti-inflammatory activity, and prevents CVDs. However, the clinical application of curcumin was limited due to its low bioavailability. This study aimed to investigate the ameliorative effects of chitosan-encapsulated curcumin (CEC) on heart and kidney damages in streptozotocin-induced type-1 diabetes C57BL/6 mice model. The results showed that Cur- and CEC-treatments downregulated the blood sugar and total cholesterol level as well as enhanced insulin secretion. However, blood pressure, triglycerides content, and very low-density lipoprotein-cholesterol content were not changed. Histochemistry analysis revealed that both curcumin and chitosan-encapsulated curcumin ameliorated cell hypertrophy and nucleus enlargement in the left ventricular of heart and reduced fibrosis in the kidney, especially after the chitosan-encapsulated curcumin treatment. Our study suggested that chitosan can effectively enhance the protective effect of curcumin on the heart and kidney damages in type-1 diabetes mice model.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Curcumina/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Quitosano/química , Curcumina/administración & dosificación , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/complicaciones , Cardiomiopatías Diabéticas/patología , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Estreptozocina
5.
Chem Asian J ; 12(18): 2471-2479, 2017 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-28688169

RESUMEN

Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and regioselective anomeric de-O-acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per-O-acetylation of unprotected sugars by using a near-stoichiometric amount of acetic anhydride under solvent-free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol resulted in a moderate-to-excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi-one-pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf)3 -catalyzed glycosylation.


Asunto(s)
Acetales/síntesis química , Carbohidratos/química , Disprosio/química , Mesilatos/química , Compuestos Organometálicos/química , Acetales/química , Acetilación , Catálisis , Estructura Molecular , Estereoisomerismo
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