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The new Brain Imaging Beamline (BIB) of the Taiwan Photon Source (TPS) has been commissioned and opened to users. The BIB and in particular its endstation are designed to take advantage of bright unmonochromatized synchrotron X-rays and target fast 3D imaging, â¼1â ms exposure time plus very high â¼0.3â µm spatial resolution. A critical step in achieving the planned performances was the solution to the X-ray induced damaging problems of the detection system. High-energy photons were identified as their principal cause and were solved by combining tailored filters/attenuators and a high-energy cut-off mirror. This enabled the tomography acquisition throughput to reach >1â mm3â min-1, a critical performance for large-animal brain mapping and a vital mission of the beamline.
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Encéfalo/diagnóstico por imagen , Imagenología Tridimensional , Traumatismos por Radiación/prevención & control , Microtomografía por Rayos X/instrumentación , Animales , Diseño de Equipo , Fotones , Sincrotrones , TaiwánRESUMEN
BACKGROUND: Nanoparticles can be used for targeted drug delivery, in particular for brain cancer therapy. However, this requires a detailed analysis of nanoparticles from the associated microvasculature to the tumor, not easy because of the required high spatial resolution. The objective of this study is to demonstrate an experimental solution of this problem, based in vivo and post-mortem whole organ imaging plus nanoscale 3-dimensional (3D) X-ray microscopy. RESULTS: The use of gold nanoparticles (AuNPs) as contrast agents paved the way to a detailed high-resolution three dimensional (3D) X-ray and fluorescence imaging analysis of the relation between xenografted glioma cells and the tumor-induced angiogenic microvasculature. The images of the angiogenic microvessels revealed nanoparticle leakage. Complementary tests showed that after endocytotic internalization fluorescent AuNPs allow the visible-light detection of cells. CONCLUSIONS: AuNP-loading of cells could be extended from the case presented here to other imaging techniques. In our study, they enabled us to (1) identify primary glioma cells at inoculation sites in mice brains; (2) follow the subsequent development of gliomas. (3) Detect the full details of the tumor-related microvasculature; (4) Finding leakage of AuNPs from the tumor-related vasculature, in contrast to no leakage from normal vasculature.
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Neoplasias Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Medios de Contraste/química , Glioma/diagnóstico por imagen , Oro/química , Nanopartículas del Metal/química , Animales , Encéfalo/irrigación sanguínea , Encéfalo/patología , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Medios de Contraste/administración & dosificación , Endocitosis , Glioma/irrigación sanguínea , Glioma/patología , Oro/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Ratones , Trasplante de Neoplasias , Imagen Óptica/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The anti-inflammatory potential of Lonicera japonica makes it an excellent source of novel medicinal targets to reduce inflammation in diabetic nephropathy. We aimed to investigate whether the ethanol extract of the flowering aerial parts of L. japonica exerts an ameliorative effect on diabetic renal inflammation using streptozotocin-induced diabetic rats. Diabetic rats were treated orally with the ethanol extract of the flowering aerial parts of L. japonica (100 and 200 mg/kg/day) for 8 weeks. The rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen, and proteinuria, along with a marked elevation in the ratio of kidney weight to body weight; all of these abnormalities were significantly reversed by the ethanol extract of the flowering aerial parts of L. japonica. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with the ethanol extract of the flowering aerial parts of L. japonica. It reduced the accumulation of ED-1-expressing macrophages in renal tissue of diabetic rats, almost completely abolished T cell infiltration and attenuated the expression of proinflammatory cytokines. The ethanol extract of the flowering aerial parts of L. japonica downregulated the protein expression of p38 mitogen-activated protein kinase in the kidney of diabetic rats. The results suggest that it has the property to inhibit the activity of p-38 MAPK-mediated inflammatory response to halt the progression of diabetic nephropathy.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Lonicera/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/patología , Riñón/efectos de los fármacos , Riñón/patología , Extractos Vegetales/uso terapéutico , RatasRESUMEN
The protective effects of ruscogenin on nonalcoholic steatohepatitis in hamsters fed a high-fat diet were investigated. Ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) was orally administered by gavage once daily for eight weeks. A high-fat diet induced increases in plasma levels of total cholesterol, triglycerides, and free fatty acids, while the degree of insulin resistance was lowered by ruscogenin. High-fat diet-induced hepatic steatosis and necroinflammation were improved by ruscogenin. Gene expression of inflammatory cytokines and activity of nuclear transcription factor-κB were also increased in the high-fat diet group, which were attenuted by ruscogenin. Ruscogenin decreased hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target genes responsible for fatty acid ß-oxidation were upregulated by ruscogenin. In conclusion, these findings suggest that ruscogenin may attenuate high-fat diet-induced steatohepatitis through anti-inflammatory mechanisms, reducing hepatic lipogenic gene expression, and upregulating proteins in the fatty acid oxidation process.
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Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Sustancias Protectoras/farmacología , Espirostanos/farmacología , Animales , Peso Corporal/efectos de los fármacos , Cricetinae , Citocinas/genética , Citocinas/metabolismo , Dieta Alta en Grasa/efectos adversos , Regulación de la Expresión Génica/efectos de los fármacos , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Oxidación-Reducción/efectos de los fármacos , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Espirostanos/administración & dosificación , Espirostanos/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triglicéridos/metabolismoRESUMEN
We investigated the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) on the inhibition of rosiglitazone (RGZ)-induced adipogenesis in 3T3-L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil-Red O in RGZ (1 µmol/l)-treated 3T3-L1 cells without or with various concentrations of 6-gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte-specific transcription factors by real-time reverse transcription-polymerase chain reaction and Western blot analysis, respectively. 6-gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ-induced adipocyte differentiation in 3T3-L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3-L1 cells was also reduced by 6-gingerol (50 µmol/l). Treatment of differentiated 3T3-L1 cells with 6-gingerol (50 µmol/l) antagonized RGZ-induced gene expression of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3-L1 cells were decreased upon treatment with 6-gingerol. Our data suggests that 6-gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down-regulating PPARγ activity.
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Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Catecoles/farmacología , Alcoholes Grasos/farmacología , Tiazolidinedionas/efectos adversos , Células 3T3-L1 , Adipocitos/citología , Adipocitos/metabolismo , Animales , Proteína alfa Potenciadora de Unión a CCAAT/antagonistas & inhibidores , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Ratones , Obesidad , PPAR gamma/antagonistas & inhibidores , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rosiglitazona , Triglicéridos/metabolismoRESUMEN
Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation.
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Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/enzimología , Dieta Alta en Grasa/efectos adversos , Emodina/farmacología , Obesidad/tratamiento farmacológico , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/genética , Adipocitos Blancos/efectos de los fármacos , Adipocitos Blancos/enzimología , Adipocitos Blancos/patología , Tejido Adiposo Blanco/patología , Animales , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/farmacología , Western Blotting , Peso Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Dieta Aterogénica/efectos adversos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Emodina/administración & dosificación , Conducta Alimentaria/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica , Metabolismo de los Lípidos , Masculino , Ratones , Obesidad/inducido químicamente , Obesidad/genética , Obesidad/metabolismo , Fosforilación , Pioglitazona , Preparaciones de Plantas/farmacología , Ratas , Ratas Wistar , Rheum/química , Índice de Severidad de la Enfermedad , Tiazolidinedionas/administración & dosificación , Triglicéridos/sangreRESUMEN
Zingiber zerumbet (L) Smith (Zingiberaceae), commonly known as the pinecone or shampoo ginger, is distributed in many parts of Asia. It has been demonstrated that the aqueous extract of Z. zerumbet exerted a potential blood glucose lowering effect in normoglycemic and streptozotocin-induced hyperglycemic rats. The present study was undertaken to clarify whether the ethanol extract of Zingiber zerumbet (EEZZ) is effective in improving insulin resistance. Insulin resistance was induced in rats by feeding a high-fructose diet for six weeks. Thereafter, rats were maintained on the same diet and treated with oral EEZZ or pioglitazone once daily for eight weeks. At the end of treatment, the degree of basal insulin resistance was measured by homeostasis model assessment (HOMA-IR). Insulin sensitivity was calculated using the composite whole body insulin sensitivity index (ISIcomp). Protein expression was evaluated by immunoblotting. Phytochemicals in EEZZ were determined through liquid chromatography-tandem mass. Not only curcumin but also quercetin and kaempferol were abundant in EEZZ. EEZZ (300 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing HOMA-IR and elevating ISIcomp as well as enhancing hepatic glycogen accumulation. Elevated glycosylated hemoglobin levels and hyperinsulinemia were ameliorated by EEZZ. Further, EEZZ enhanced the action of insulin on muscle glucose transporter subtype 4 translocation and attenuated hepatic phosphoenolpyruvate carboxykinase expression. This study suggests that EEZZ may be an ethnomedicine for improving insulin sensitivity.
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Resistencia a la Insulina , Extractos Vegetales/farmacología , Zingiberaceae/química , Animales , Fructosa/administración & dosificación , Hipoglucemiantes/farmacología , Masculino , Pioglitazona , Ratas , Ratas Wistar , Tiazolidinedionas/farmacologíaRESUMEN
The objective of this study was to evaluate the acute and subacute toxicity (28 days) of the ethanol extract of Z. zerumbet rhizomes (EEZZ) via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg(-1) of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg(-1). In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg(-1) for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe.
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The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of myricetin. Myricetin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes. The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate, once daily for eight weeks. Myricetin (300 mg kg(-1) per day) displayed similar characteristics to fenofibrate (100 mg kg(-1) per day) in reducing lowered body weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor (PPAR)α. HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results suggest that myricetin suppressed BW gain and body fat accumulation by increasing the fatty acid oxidation, which was likely mediated via up-regulation of PPARα and down-regulation of SREBP expressions in the liver of HFD-fed rats.
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The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of emodin on high-fat diet (HFD)-induced obese rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed HFD for two weeks, Wistar rats were dosed orally with emodin (40 and 80 mg kg(-1)) or pioglitazone (20 mg kg(-1)), once daily for eight weeks. Emodin (80 mg kg(-1) per day) displayed similar characteristics to pioglitazone (20 mg kg(-1) per day) in reducing body weight gain, plasma lipid levels as well as coronary artery risk index and atherogenic index of HFD-fed rats. Emodin also caused dose related reductions in the hepatic triglyceride and cholesterol contents and lowered hepatic lipid droplets accumulation in HFD-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in hepatocytes of HFD-fed rats. Our findings suggest emodin could attenuate lipid accumulation by decreasing lipogenesis and increasing mitochondrial fatty acid ß-oxidation mediated by activation of the AMPK signaling pathway.
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The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of vinegar-baked Radix Bupleuri (VBRB) on high-fat diet- (HFD-) induced obese rats. After being fed HFD for two weeks, rats were dosed orally with VBRB or fenofibrate, once daily for further twelve weeks. VBRB (1.0 g kg(-1) per day) produced effects similar to fenofibrate (100 mg kg(-1)) in reducing body weight (BW) gain, visceral fat-pad weights, plasma lipid levels, as well as hepatic TG and cholesterol content of HFD-fed rats. VBRB also lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. VBRB and fenofibrate reversed the HFD-induced downregulation of hepatic peroxisome proliferator-activated receptor (PPAR)α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by VBRB and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats was lowered by VBRB and fenofibrate. The results of this study show that VBRB suppresses BW gain and body fat accumulation by increasing fatty acid oxidation, an effect which is likely mediated via upregulation of PPARα and downregulation of SREBP expression in the liver of HFD-fed rats.
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The present study was undertaken to characterize the effects of Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines, on diabetic nephropathy. Streptozotocin-induced diabetic rats were orally administrated DSS (2.8 g kg(-1) per day) for 12 consecutive weeks. DSS partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-hour urinary albumin excretion rate, and creatinine clearance as well as the kidney hypertrophy (kidney weight/body weight ratio) and glomerular mesangial matrix expansion were ameliorated after 12 weeks of DSS treatment. The increased expression of nuclear factor-κB as well as transforming growth factor-ß(1) and the progressive accumulation of type IV collagen in kidney of diabetic rats were also attenuated by DSS. Not only the elevated levels of advanced glycation end products (AGEs) and N(ε)-(carboxymethyl)lysine but also the higher levels of lipid peroxidation products in kidney of diabetic rats were ameliorated by DSS. Decreased activity of superoxide diamutase and glutathione peroxidase in kidney of diabetic rats was enhanced by DSS. These data demonstrated that the renoprotective effects of DSS in STZ-diabetic rats not only were attributable to regulate plasma glucose to attenuate AGEs expression in diabetic glomeruli but also likely reflected its antioxidant activity.
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The present study evaluated the potential genotoxicity of the ethanol extracts from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) using a standard battery of tests. Chemical analysis with liquid chromatography-tandem mass spectrometry revealed that EEZZR contained Zerumbone (200.3 ± 0.37 µg/g) and 6-gingerol (102.5 ± 0.28 µg/g). There were no increases in the number of revertant colonies with EEZZR at concentrations of 150-5000 µg per plate, regardless of the metabolic activation system (S-9 mix) used in the histidine-dependent auxotrophic mutants of Salmonella typhimurium (strains TA97, TA98, TA100, TA102, and TA1535) compared to the vehicle control. Furthermore, EEZZR at doses of 150-5000 µg mL(-1) did not increase the number of structural aberrations in Chinese hamster lung cells in the presence or absence of S-9 mix. An oral administration of EEZZR to ICR mice, with doses of up to 2000 mg/kg, caused no significant increases in the number of micronucleated polychromatic erythrocytes (MNPCEs) and mean ratio of polychromatic erythrocytes to total erythrocytes. Lastly, RZZEE did not increase the incidence of MNPCEs in bone marrow. Based on these findings, it may be concluded that the use of EEZZR in traditional medicine poses no risk of genotoxicity.
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The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of Angelica acutiloba root (Japanese Dong Quai). High-fat diet (HFD)-induced obese rats were treated orally with the polyphenolic-rich extract of Angelica acutiloba root (AARE) once daily for 8 weeks. The AARE (300 mg/kg per day) supplementation significantly lowered body weight gain, visceral fat-pad weights and plasma lipid levels, as well as the coronary artery risk index and the atherogenic index of HFD-fed rats. The AARE caused dose related reductions in the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplet accumulation and epididymal adipocyte size in the HFD-fed rats. The AARE reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor-α (PPARα). The HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase (ACO), and the cytochrome P450 isoform 4A1 (CYP4A1) was up-regulated by AARE. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by AARE. These results suggest that AARE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obesity by increasing lipid metabolism through the down-regulation of SREBPs and enhanced the expression of ACO and CYP4A1 in the liver, which was likely mediated by up-regulation of the expression of hepatic PPARα.
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Angelica/química , Fármacos Antiobesidad/farmacología , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Grasa Intraabdominal/efectos de los fármacos , Metabolismo de los Lípidos , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacosRESUMEN
Microscopy by Achromatic X-rays With Emission of Laminar Light (MAXWELL) is a new X-ray/visible technique with attractive characteristics including isotropic resolution in all directions, large-volume imaging and high throughput. An ultrathin, laminar X-ray beam produced by a Wolter type I mirror irradiates the sample stimulating the emission of visible light by scintillating nanoparticles, captured by an optical system. Three-dimensional (3D) images are obtained by scanning the specimen with respect to the laminar beam. We implemented and tested the technique with a high-brightness undulator at SPring-8, demonstrating its validity for a variety of specimens. This work was performed under the Synchrotrons for Neuroscience-an Asia-Pacific Strategic Enterprise (SYNAPSE) collaboration.
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Microscopía , Sincrotrones , Imagenología Tridimensional , Luz , Microscopía/métodos , Tomografía Computarizada por Rayos X/métodos , Rayos XRESUMEN
The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of the flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone). After being fed a high-fat diet (HFD) for two weeks, rats were dosed orally with kaempferol (75, 150, or 300 mg/kg) or fenofibrate (100 mg/kg) once daily for eight weeks. Fenofibrate is an antilipemic agent that exerts its therapeutic effects through activation of peroxisome proliferator-activated receptor α (PPAR α). Kaempferol (300 mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights, plasma lipid levels, as well as the coronary artery risk and atherogenic indices of HFD-fed rats. Kaempferol also caused dose-related reductions in hepatic triglyceride and cholesterol content and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. Kaempferol and fenofibrate reversed the HFD-induced downregulation of hepatic PPAR α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO), and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by kaempferol and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats were lowered by kaempferol and fenofibrate. These results suggest that kaempferol reduced the accumulation of visceral fat and improved hyperlipidemia in HFD-fed obese rats by increasing lipid metabolism through the downregulation of SREBPs and promoting the hepatic expression of ACO and CYP4A1, secondary to a direct upregulation hepatic PPAR α expression.
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Regulación de la Expresión Génica/efectos de los fármacos , Hipolipemiantes/farmacología , Quempferoles/farmacología , Hígado/fisiopatología , PPAR alfa/metabolismo , Acil-CoA Oxidasa/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Administración Oral , Animales , Citocromo P-450 CYP4A/metabolismo , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Fenofibrato/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
Angelica acutiloba root (Japanese Dong Quai), used for treatment of gynecological disorders, is currently cultivated in Taiwan. The present study evaluated the preventative effect of Angelica acutiloba root (Japanese Dong Quai) on the induction of insulin resistance. Insulin resistance was induced in rats by feeding a high fructose diet for 6 weeks. Thereafter, the rats were maintained on the same diet and treated with oral A. acutiloba root extract or pioglitazone once daily for 8 weeks. At the end of treatment, the degree of basal insulin resistance was measured by homeostasis model assessment (HOMA-IR). Insulin sensitivity was calculated using the composite whole body insulin sensitivity index (ISIcomp). Protein expression was evaluated by immunoblotting. A. acutiloba (300 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing HOMA-IR and elevating ISIcomp. Elevated glycosylated hemoglobin levels and hyperinsulinemia were ameliorated by A. acutiloba treatment without hepatotoxic or nephrotoxic effects. A. acutiloba treatment improved dyslipidemia, induced lipoprotein lipase activity and enhanced hepatic glycogen accumulation. Further, A. acutiloba treatment enhanced the action of insulin on muscle glucose transporter subtype 4 translocation and attenuated hepatic phosphoenolpyruvate carboxykinase expression. The findings suggest that A. acutiloba may be an effective ethnomedicine for improving insulin sensitivity.
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Angelica/química , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Extractos Vegetales/farmacología , Animales , Peso Corporal , Fructosa/efectos adversos , Prueba de Tolerancia a la Glucosa , Transportador de Glucosa de Tipo 4/metabolismo , Glucógeno/química , Homeostasis , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Lípidos/química , Hígado/química , Hígado/efectos de los fármacos , Masculino , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Pioglitazona , Raíces de Plantas/química , Ratas Wistar , Tiazolidinedionas/farmacologíaRESUMEN
RATIONALE AND OBJECTIVES: Breast cancer occurs more frequently in the upper outer (UO) quadrant, but whether this higher cancer incidence is related to the greater amount of dense tissue is not known. Magnetic resonance imaging acquires three-dimensional volumetric images and is the most suitable among all breast imaging modalities for regional quantification of density. This study applied a magnetic resonance imaging-based method to measure quadrant percent density (QPD), and evaluated its association with the quadrant location of the developed breast cancer. MATERIALS AND METHODS: A total of 126 cases with pathologically confirmed breast cancer were reviewed. Only women who had unilateral breast cancer located in a clear quadrant were selected for analysis. A total of 84 women, including 47 Asian women and 37 western women, were included. An established computer-aided method was used to segment the diseased breast and the contralateral normal breast, and to separate the dense and fatty tissues. Then, a breast was further separated into four quadrants using the nipple and the centroid as anatomic landmarks. The tumor was segmented using a computer-aided method to determine its quadrant location. The distribution of cancer quadrant location, the quadrant with the highest QPD, and the proportion of cancers occurring in the highest QPD were analyzed. RESULTS: The highest incidence of cancer occurred in the UO quadrant (36 out of 84, 42.9%). The highest QPD was also noted most frequently in the UO quadrant (31 out of 84, 36.9%). When correlating the highest QPD with the quadrant location of breast cancer, only 17 women out of 84 (20.2%) had breast cancer occurring in the quadrant with the highest QPD. CONCLUSIONS: The results showed that the development of breast cancer in a specific quadrant could not be explained by the density in that quadrant, and further studies are needed to find the biological reasons accounting for the higher breast cancer incidence in the UO quadrant.
Asunto(s)
Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Mama/diagnóstico por imagen , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Mama/patología , Neoplasias de la Mama/patología , Estudios de Evaluación como Asunto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
RATIONALE AND OBJECTIVES: Low-dose chest computed tomography (LDCT), increasingly being used for screening of lung cancer, may also be used to measure breast density, which is proven as a risk factor for breast cancer. In this study, we developed a segmentation method to measure quantitative breast density on CT images and correlated with magnetic resonance density. MATERIALS AND METHODS: Forty healthy women receiving both LDCT and breast magnetic resonance imaging (MRI) were studied. A semiautomatic method was applied to quantify the breast density on LDCT images. The intra- and interoperator reproducibility was evaluated. The volumetric density on MRI was obtained by using a well-established automatic template-based segmentation method. The breast volume (BV), fibroglandular tissue volume (FV), and percent breast density (PD) measured on LDCT and MRI were compared. RESULTS: The measurements of BV, FV, and PD on LDCT images yield highly consistent results, with the intraclass correlation coefficient of 0.999 for BV, 0.977 for FV, and 0.966 for PD for intraoperator reproducibility, and intraclass correlation coefficient of 0.953 for BV, 0.974 for FV, and 0.973 for PD for interoperator reproducibility. The BV, FV, and PD measured on LDCT and MRI were well correlated (all r ≥ 0.90). Bland-Altman plots showed that a larger BV and FV were measured on LDCT than on MRI. CONCLUSIONS: The preliminary results showed that quantitative breast density can be measured from LDCT, and that our segmentation method could yield a high reproducibility on the measured volume and PD. The results measured on LDCT and MRI were highly correlated. Our results showed that LDCT may provide valuable information about breast density for evaluating breast cancer risk.
Asunto(s)
Densidad de la Mama/fisiología , Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Mama/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Dosis de Radiación , Reproducibilidad de los ResultadosRESUMEN
Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone), a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 µmol/L) treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate)-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day) once daily for another four weeks. 6-Gingerol (100 mg/kg/day) attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB), which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.