RESUMEN
Considering the absence of prior studies on the cholesterol metabolism-improving effects of eugeniin, the present investigation aimed to explore the potential impact of eugeniin on cholesterol metabolism. This study sought to elucidate the molecular mechanisms involved in this process using HepG2 and Caco-2 cells treated with 5 µm eugeniin. The intracellular cholesterol levels in HepG2 and Caco-2 cells were significantly decreased in the 24-h eugeniin-treated group. The protein and messenger ribonucleic acid (mRNA) levels of the low-density lipoprotein receptor (LDLR) were increased, while 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase protein and mRNA levels were decreased in HepG2 cells 6 h of the eugeniin-treated group. Additionally, LDLR protein and mRNA levels were increased in HepG2 cells after 24 h of eugeniin treatment. In Caco-2, the protein and mRNA levels of ATP-binding cassette transporter 1 were increased after 24 h eugeniin treatment. This novel finding indicates that eugeniin improves cholesterol metabolism in human cell cultures.
Asunto(s)
Colesterol , Hidroximetilglutaril-CoA Reductasas , Humanos , Células CACO-2 , Colesterol/metabolismo , Células Hep G2 , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Obesity presents a major risk factor in the development of cardiovascular diseases. Recent reports indicate that many kinds of polyphenols have the potential to prevent metabolic diseases. We hypothesized that rose polyphenols (ROSE) have the effect of improvement in lipid metabolism. In this study, we investigated whether rose polyphenols affected lipid metabolism and exerted antiobesity. To clarify the mechanism, C57BL/6J mice were fed a high-fat diet containing 0.25% ROSE for 35 days. Compared with the control group, body weight gain and adipose tissue weight in the 0.25% ROSE group were significantly decreased. Serum cholesterol and hepatic triglyceride concentrations significantly decreased, whereas fecal triglyceride was significantly increased in the 0.25% ROSE group. Liver stearoyl-CoA desaturase 1 (Scd1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and acyl-CoA:cholesterol acyltransferase 1 (Acat1) mRNA as well as protein stearoyl-CoA desaturase 1 concentrations were significantly lower in the 0.25% ROSE group than that in the control group. The mRNA and the protein concentrations of adipose triglyceride lipase, hormone-sensitive lipase, and peroxisomal acylcoenzyme A oxidase 1 in white adipose tissue were significantly higher in the 0.25% ROSE group than that in the control group. The components in rose polyphenols were quantified by liquid chromatography-tandem mass spectrometry, and we consider that ellagic acid plays an important role in an antiobesity effect because the ellagic acid content is the highest among polyphenols in rose polyphenols. In summary, rose polyphenols exhibit antiobesity effects by influencing lipid metabolism-related genes and proteins to promote lipolysis and suppress lipid synthesis.
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Polifenoles , Estearoil-CoA Desaturasa , Ratones , Animales , Ratones Obesos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , Ácido Elágico/metabolismo , Ácido Elágico/farmacología , Ratones Endogámicos C57BL , Tejido Adiposo/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Triglicéridos , ARN Mensajero/metabolismo , Expresión GénicaRESUMEN
In the context of the growing prevalence of type 2 diabetes (T2DM), control of postprandial hyperglycemia is crucial for its prevention. Blood glucose levels are determined by various factors including carbohydrate hydrolyzing enzymes, the incretin system and glucose transporters. Furthermore, inflammatory markers are recognized predictors of diabetes outcome. Although there is some evidence that isoflavones may exhibit anti-diabetic properties, little is known about to what extent their corresponding hydroxylated metabolites may affect glucose metabolism. We evaluated the ability of a soy extract before (pre-) and after (post-) fermentation to counteract hyperglycemia in vitro and in Drosophila melanogaster in vivo. Fermentation with Aspergillus sp. JCM22299 led to an enrichment of hydroxy-isoflavones (HI), including 8-hydroxygenistein, 8-hydroxyglycitein and 8-hydroxydaidzein, accompanied by an enhanced free radical scavenging activity. This HI-rich extract demonstrated inhibitory activity towards α-glucosidase and a reduction of dipeptidyl peptidase-4 enzyme activity. Both the pre- and post-fermented extracts significantly inhibited the glucose transport via sodium-dependent glucose transporter 1. Furthermore, the soy extracts reduced c-reactive protein mRNA and secreted protein levels in interleukin-stimulated Hep B3 cells. Finally, supplementation of a high-starch D. melanogaster diet with post-fermented HI-rich extract decreased the triacylglyceride content of female fruit flies, confirming its anti-diabetic properties in an in vivo model.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Isoflavonas , Animales , Femenino , Drosophila melanogaster/metabolismo , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/prevención & control , Isoflavonas/farmacología , Isoflavonas/metabolismo , Extractos Vegetales/farmacología , GlucosaRESUMEN
Koopman mode decomposition (KMD) is a technique of nonlinear time-series analysis capable of decomposing data on complex spatiotemporal dynamics into multiple modes oscillating with single frequencies, called the Koopman modes (KMs). We apply KMD to measurement data on oscillatory dynamics of a temperature field inside a room that is a complex phenomenon ubiquitous in our daily lives and has a clear technological motivation in energy-efficient air conditioning. To characterize not only the oscillatory field (scalar field) but also associated heat flux (vector field), we introduce the notion of a temperature gradient using the spatial gradient of a KM. By estimating the temperature gradient directly from data, we show that KMD is capable of extracting a distinct structure of the heat flux embedded in the oscillatory temperature field, relevant in terms of air conditioning.
RESUMEN
OBJECTIVE: Namilumab is an investigational human monoclonal antibody to human granulocyte-macrophage colony-stimulating factor (GM-CSF). A phase I study of repeated namilumab dosing (150 or 300 mg subcutaneously) in non-Japanese patients with rheumatoid arthritis reported no safety concerns. The objective of this study was to report the safety (primary endpoint) and pharmacokinetic/pharmacodynamic effects of namilumab in healthy Japanese and Caucasian men aged 20 - 45 years (NCT02354599). MATERIALS AND METHODS: 24 Japanese subjects were randomized to a single dose of namilumab (80, 150, or 300 mg; n = 6/group) or placebo (n = 6; 2 subjects randomized/matched dose); 8 Caucasian subjects received namilumab 150 mg (n = 6) or placebo (n = 2). RESULTS: Overall, 29 subjects completed the study (2 withdrew voluntarily; 1 due to a serious adverse event (AE) unrelated to treatment). Baseline demographics were similar across treatment groups; mean age and weight were higher in Caucasians. Namilumab was well tolerated, with no notable safety concerns or pharmacokinetic/pharmacodynamic differences between Japanese and Caucasian subjects. AEs were mild to moderate, with no dose-proportional increase in Japanese subjects. Area under the serum concentration-time curve from zero to infinity (AUC0-∞) and maximum serum concentration (Cmax) increased in a dose-proportional manner in Japanese subjects. AUC0-∞ was similar in Japanese (575.2 µg×day/mL) and Caucasian (559.7 µg×day/mL) 150-mg groups. Cmax was ~ 40% higher in Japanese subjects. Mean plasma total GM-CSF concentration-time profiles were similar in the Japanese and Caucasian 150-mg groups. Namilumab induced no clinically-relevant antibody response. CONCLUSION: Namilumab was well tolerated in Japanese and Caucasian subjects; namilumab 150 mg had similar pharmacokinetics in both populations, supporting further clinical development of this dose.â©.
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Anticuerpos Monoclonales/farmacocinética , Antirreumáticos/farmacocinética , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Antirreumáticos/efectos adversos , Área Bajo la Curva , Pueblo Asiatico , Método Doble Ciego , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Masculino , Persona de Mediana Edad , Población Blanca , Adulto JovenRESUMEN
In a previous study, we reported the effectiveness of a bacterial strain showing monolayer adsorption to oil surfaces on microbial conversion at oil-water interfaces. In the present study, we screened wild type strains from our toluene-degrading bacterial library that showed similar properties and succeeded in obtaining five wild type strains that adsorb to oil surfaces as a cell monolayer. We investigated the effects of cultivation conditions on cell surface hydrophobicity of these five strains. The effects of substrate hydrophobicity and the porous carrier were not significant. By contrast, growth temperature greatly affected the cell surface hydrophobicity of all five strains, especially strain TIS1-127, which was phylogenetically identified as Pseudomonas sp. which is closely related to P. mosselii, P. monteilii, and P. plecoglossicida. Pseudomonas sp. TIS1-127 cells grown at 37 degrees C were determined by the kinetic microbial-adhesion-to-hydrocarbon (MATH) test to be fully hydrophilic (lower than 10% of MATH value) while the cells grown at 28 degrees C were highly hydrophobic (over 90% of MATH value). We investigated the effects of growth temperature on toluene conversion by TIS1-127 resting cells in single-phase batch cultivation and in two-liquid-phase partitioning reactors containing an emulsion consisting of 20% silicone oil and 80% cell suspension. In both cases, the cells grown at 28 degrees C showed much higher conversion ability than those grown at 37 degrees C. Toluene conversion followed Michaelis-Menten kinetics and the K(m) values for the cells grown at 28 degrees C were lower than 1/10 those for the cells grown at 37 degrees C.