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1.
Int J Med Sci ; 17(6): 815-823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218703

RESUMO

Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in Ipo11 gene utilized by gene trapping. The Ipo11-/- embryos showed an embryonic lethal phenotype. The Ipo11-/- embryos showed a reduced size at embryonic day 10.5 (E10.5) when compared with Ipo11+/+ or Ipo11+/- embryos and died by E11.5. Whereas Ipo11+/- mice were healthy and fertile, and there was no detectable changes in embryonic lethality and phenotype when reviewed. In the X-gal staining with the Ipo11-/- or Ipo11+/- embryos, strong X-gal staining positivity was detected systematically in the whole mount embryos at E10.5, although almost no X-gal positivity was detected at E9.5, indicating that the embryos die soon after the process of Ipo11 expression started. These results indicate that Ipo11 is essential for the normal embryonic development in mice.

2.
Molecules ; 25(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098445

RESUMO

Positive physiological benefits of several plant oils on the UV-induced photoaging have been reported in some cell lines and model mice, but perilla oil collected from the seeds of Perilla frutescens L. has not been investigated in this context. To study the therapeutic effects of cold-pressed perilla oil (CPO) on UV-induced photoaging in vitro and in vivo, UV-induced cellular damage and cutaneous photoaging were assessed in normal human dermal fibroblasts (NHDFs) and HR-1 hairless mice. CPO contained five major fatty acids including linolenic acid (64.11%), oleic acid (16.34%), linoleic acid (11.87%), palmitic acid (5.06%), and stearic acid (2.48%). UV-induced reductions in NHDF cell viability, ROS production, SOD activity, and G2/M cell cycle arrest were remarkably improved in UV + CPO treated NHDF cells as compared with UV + Vehicle treated controls. Also, UV-induced increases in MMP-1 protein and galactosidase levels were remarkably suppressed by CPO. In UV-radiated hairless mice, topical application of CPO inhibited an increase in wrinkle formation, transepidermal water loss (TEWL), erythema value, hydration and melanin index on dorsal skin of UVB-irradiated hairless mice. CPO was observed to similarly suppress UV-induced increases in epidermal thickness, mast cell numbers, and galactosidase and MMP-3 mRNA levels. These results suggest CPO has therapeutic potential in terms of protecting against skin photoaging by regulating skin morphology, histopathology and oxidative status.

3.
Mol Med Rep ; 21(3): 1346-1355, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894328

RESUMO

AlaskOmega® Omega 7 500, also known as Omega­7 fatty acid or 7­MEGA™, is a highly concentrated palmitoleic acid (C16:1). Little is known about how 7­MEGA regulates skin inflammation and wrinkle formation in cultured skin cells. The present study aimed to investigate the effects of 7­MEGA on the expression of cyclooxygenase­2 (COX­2), matrix metallopeptidase (MMP)­1/3 and type 1 procollagen, which are markers of skin inflammation and wrinkle formation, in ultraviolet B (UVB)­irradiated human dermal fibroblasts (HDFs) and keratinocytes (HaCaT). No toxicity was observed upon treatment of HDFs and HaCaT cells with 0.5­2.5 µl/ml 7­MEGA. The exposure of HaCaT cells to 10 mJ/cm2 UVB for 6 h resulted in increased protein and/or mRNA expression of COX­2 and MMP­3. Treatment of HaCaT cells with 2.5 µl/ml 7­MEGA suppressed the UVB­induced expression of COX­2 and MMP­3 in these cells. In addition, treatment with 2.5 µl/ml 7­MEGA attenuated the UVB­induced expression and phosphorylation levels of c­Fos and c­Jun, two components of the activator protein­1 (AP­1) transcription factor, in HaCaT cells. Exposure of HDFs to 60 mJ/cm2 UVB for 6 h significantly decreased the expression of type 1 procollagen protein, whereas treatment with 2.5 µl/ml 7­MEGA partially reversed the effects of UVB on the expression of type 1 procollagen protein. These results demonstrated for the first time that 7­MEGA regulated the expression of COX­2, MMP­3 and type 1 procollagen in UVB­irradiated skin cells. The present study suggested that 7­MEGA may serve as a novel agent against UVB­induced skin inflammation and damage.

4.
Toxicol In Vitro ; 63: 104675, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31648046

RESUMO

In order to overcome the limitations of single in vitro eye irritation tests, Integrated Approaches to Testing Assessment strategies have been suggested for evaluating eye irritation. This study developed two tiered approaches combining alternative test methods. They were designed in consideration of the solubility property of test chemicals and to use the RhCE tests at final steps. The tiered approach A is composed of the STE, BCOP, HET-CAM or RhCE tests, whereas the tiered approach B is designed to perform simultaneously two in vitro test methods at the first stage and the RhCE test at the final stage. The predictive capacity of the two tiered approaches was estimated using 47 chemicals. The accuracy, sensitivity, and specificity value of the tiered approach A were 95.7% (45/47), 100% (34/34), and 84.6% (11/13), respectively, whereas those of the tiered approach B were 95.7% (45/47), 97.1% (33/34), and 92.3% (12/13), respectively. The approach A and B were considered to be available methods for distinguishing test chemicals of Category 1 (all 73.3%) and No Category (84.6% and 92.3%), respectively. Especially, the approach B was considered as an efficient method as the Bottom-Up approach, because it predicted correctly test chemicals classified as No Category.

5.
Toxicol Res ; 35(4): 353-359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31636846

RESUMO

The purpose of this study was to investigate the effect of 7-MEGA™ 500 on the improvement of skin aging in an UVB-induced photo-aging model of hairless mice. The dorsal skin of hairless mice was exposed to UVB three times a week for 12 weeks to induce skin wrinkle. After inducing the wrinkle, 7-MEGA™ 500 was orally administered once a day for 4 weeks. Skin thickness, skin barrier function, and wrinkle indicators were improved by treatment with 7-MEGA™ 500. Both gene and protein expression levels of MMP-3 and c-Jun in skin were significantly decreased by 7-MEGA™ 500. Therefore, the intake of 7-MEGA™ 500 is thought to have a positive effect on the improvement of skin aging, although further studies are needed.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30903998

RESUMO

BACKGROUND: Maqui berry (Aristotelia chilensis) has been reported to have anti-glycation, anti-inflammation, lipogenesis-inhibiting activities highly related to its anti-oxidation function, but practical efficacy studies on immunological mechanisms for atopic dermatitis, have not been reported yet. OBJECTIVE: This study investigated the immune regulation mechanism of Aristotelia chilensis water extract (ACWE) related to atopic-like dermatitis METHODS: Antioxidant and anti-inflammatory effects of ACWE was assayed. Atopy inhibitory effect was evaluated using in vitro cell study and in vivo 2,4-dinitrochlorobenzene (DNCB)-induced mouse atopic-like dermatitis model. RESULTS: ACWE has good antioxidant activities, and atopic indications were improved in ACWE group in DNCB-induced atopic-like dermatitis model of BALB/c mice. In spleen cells from mice, ACWE increased interferon-gamma (IFN-γ) levels, and decreased interleukin-4 (IL-4) levels compared with the DNCB control. CONCLUSION: ACWE was efficacious for atopic dermatitis which indicates that ACWE might have potential as an agent for atopic dermatitis.

7.
Food Chem Toxicol ; 121: 360-366, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30213554

RESUMO

Permanent oxidative hair dyes are widely used but their toxicity is not well-established. Here we aimed to evaluate the skin sensitization and irritation of nine hair dye substances (MAP, MRP-N, RS, PAOX, 2,4-DAPE, 2,6-PYR, PPD, Grey HED and PM) permitted for use in EU and Korea, using in vitro and in chemico and in silico test methods. Skin sensitization was evaluated by the KeratinoSens™ assay, Direct Peptide Reactivity Assay (DPRA) and DEREK. Six of nine dyes tested were determined as sensitizers in common. However, the decision for MAP, RS or PAOX was diverged across assays showing 2 positives and 1 negative. Skin irritation of hair dye substances was assessed with or without 6% H2O2 on a reconstructed human epidermis, Epiderm™, which demonstrated that H2O2 increased the skin irritation potential of some hair dyes. PPD and PM were determined to be irritants with H2O2. Epidermal damages by hair dye and H2O2 could be further confirmed through the histology of tissue remaining after MTT assay. Collectively, our study demonstrated that hair dyes possess potential skin sensitization and irritation issues which could be further aggravated by H2O2.


Assuntos
Tinturas para Cabelo/química , Oxidantes/toxicidade , Testes de Irritação da Pele , Bioensaio , Simulação por Computador , Dermatite Alérgica de Contato , União Europeia , Humanos , Irritantes , Oxidantes/química , Estresse Oxidativo , República da Coreia , Pele/efeitos dos fármacos
8.
Toxicol Res ; 34(2): 97-102, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29686771

RESUMO

The objective of this study was to determine the oral wound healing effects of acai berry water extracts (ABWE) in rat oral mucosa. To estimate the anti-oxidative effects of ABWE, the contents of phenolic compounds, and DPPH (1,1-diphenyl-2-picryl hydrazyl) and ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) abilities were evaluated. Wound healing effects of ABWE were tested following 6-day exposure after induction of wound by applying 50% acetic acid to oral mucosa of Sprague-Dawley rats. Macroscopic and histopathological analyses were performed to determine wound healing effects of ABWE. Sodium fusidate (20 mg/g) was used as positive control. ABWE showed significantly high antioxidant effects in all assays, although its potency was weaker than the positive control. From day 3 after treatment, wound healing effects of ABWE were observed in oral mucosa. These wound healing effects were also consistent with histopathological evaluation results. Taken together, these results indicate that ABWE might have potential as an oral wound healing agent in the future.

9.
Toxicol Res ; 33(2): 149-156, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28503264

RESUMO

The purpose of this study was to investigate the wound healing effect of acai berry water extracts (ABWE) and a possible underlying mechanism involved in its action using various in vitro and in vivo models. The wound healing effect of ABWE was evaluated by migration assay using HS68 fibroblast cells. In addition, its effect on mRNA expression of procollagen, fibronectin, and MMP-1 was determined. Moreover, the wound healing effect of ABWE was evaluated in in vivo wound models through macroscopic and microscopic observation. In addition, mRNA expression levels of wound related genes were determined. Results revealed that ABWE was not cytotoxic. It increased migration of HS68 fibroblast cells. ABWE increased mRNA expression levels of fibronectin but decreased the mRNA expression levels of MMP-1. ABWE also showed significantly potent wound healing effect in vivo based on macroscopic and histopathological observation and mRNA expression evaluation for wound related genes. Taken together, our results indicated that ABWE might have potential as a wound healing agent.

10.
J Expo Sci Environ Epidemiol ; 27(3): 320-325, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27436697

RESUMO

The objective of this study was to evaluate the permeation of paraben derivatives - methylparaben (MP), propylparaben (PP), and butylparaben (BP) - in hairless mouse full skin and human cadaver epidermis using a Franz diffusion cell method, which is proposed as a reliable alternative method to an skin absorption test. Parabens, esterified hydroxybenzoic acid compounds, are widely used as preservatives in food, cosmetics, and pharmaceutical products. The skin permeation rate showed dose dependency, and the hairless mouse full skin showed a higher flux value than human cadaver epidermis. Among the permeability coefficient (Kp) values of three parabens, MP showed a higher Kp value than PP or BP. Hence, according to the definitions of Marzulli et al., parabens would be classified as "moderate" penetrants.


Assuntos
Parabenos/metabolismo , Conservantes Farmacêuticos/metabolismo , Absorção Cutânea/efeitos dos fármacos , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Pelados , Permeabilidade , Pele
11.
Int J Mol Med ; 38(5): 1565-1577, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27665714

RESUMO

Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCT­treated groups compared with the UV + vehicle­treated group, and the expression of collagen I increased. The attenuation of mitogen­activated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCT­treated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT-treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for use as therapeutic drug which protects against skin aging by regulating the skin morphology, histopathological structures, ER stress, inflammation and oxidative conditions.


Assuntos
Antioxidantes/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Urocordados/química , Animais , Western Blotting , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos da radiação , Epiderme/efeitos dos fármacos , Epiderme/patologia , Epiderme/efeitos da radiação , Etanol/química , Flavonoides/análise , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Masculino , Camundongos Pelados , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fenóis/análise , Substâncias Protetoras/farmacologia , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/fisiologia , Envelhecimento da Pele/efeitos da radiação , Superóxido Dismutase/metabolismo , Extratos de Tecidos/isolamento & purificação , Raios Ultravioleta , Perda Insensível de Água/efeitos dos fármacos , Perda Insensível de Água/efeitos da radiação
12.
Toxicol Res ; 32(3): 259-67, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27437094

RESUMO

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials.

13.
Biosci Biotechnol Biochem ; 79(6): 919-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25685961

RESUMO

Adipose-derived mesenchymal stem cells (AdMSCs) have been reported to have therapeutic benefit in skin. The aim of this study was to examine the effects of AdMSCs in UV-irradiated human dermal fibroblasts (HDFs) for therapeutic potential in skin wrinkling. UV irradiation, a model naturally mimic skin wrinkle formation, is known to increase matrix metalloproteinase-1 (MMP-1), making MMP-1 a target for skin photoaging. Our findings identified that AdMSCs reduce MMP-1 level in UV-irradiated HDFs and increase type 1 procollagen in HDFs. A dose-dependent increase in type 1 procollagen was confirmed by AdMSC-conditioned medium. Importantly, our current findings showing the effects of AdMSCs on the induction of MMP-1 in UV-radiated HDFs and the expression of collagen in HDFs can provide an evidence of relationship between MMP-1 and procollagen production for the protection against wrinkle formation. Collectively, AdMSCs may contribute to anti-wrinkle effects in skin but further experiments are needed to identify the mechanism.


Assuntos
Fibroblastos/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Envelhecimento da Pele/efeitos da radiação , Pele/citologia , Raios Ultravioleta/efeitos adversos , Tecido Adiposo/citologia , Proliferação de Células/efeitos da radiação , Técnicas de Cocultura , Colágeno Tipo I/metabolismo , Meios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos da radiação , Humanos , Pró-Colágeno/metabolismo , Pele/efeitos da radiação
14.
Biosci Biotechnol Biochem ; 77(8): 1694-702, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23924732

RESUMO

This study investigated the effects of administering poly-γ-glutamic acid (γ-PGA), isoflavones, and γ-PGA with isoflavones on the lipid, fatty liver, and gene expression levels associated with fatty acid oxidation and adipose synthesis in high-fat diet (HFD)-induced C57BL/6 mice. The results demonstrate a significant decrease in the body weight gain, food intake, food efficiency, liver weight, and epididymal adipose tissue of the experimental groups in comparison with the HFD-induced control group. The serum biochemistry indices for hepatic damage, hyperlipidemia, hyperglycemia, and lipid deposits in the liver and adipose tissue were also lower in the experimental groups than in the control group. The anti-oxidative index, and cytokine and enzyme levels associated with obesity (e.g., leptin, adiponectin, AMPK, CPT-1, PPARα, GLUT-4, and UCP-2) were enhanced in the experimental groups in comparison with the control group. These results demonstrate that γ-PGA and isoflavones improved the blood lipid level, insulin resistance, and hyperglycemia. Increased fatty acid oxidation inhibited the synthesis and accumulation of adipose tissue. The results suggest that γ-PGA and isoflavones could be used as new functional foods for preventing obesity.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Isoflavonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Obesos/metabolismo , Ácido Poliglutâmico/administração & dosagem , Animais , Fármacos Antiobesidade/administração & dosagem , Dieta Hiperlipídica , Humanos , Camundongos , Obesidade/metabolismo , Obesidade/patologia , Ácido Poliglutâmico/análogos & derivados
15.
Biochem Biophys Res Commun ; 434(3): 589-93, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23583385

RESUMO

The Sleeping Beauty (SB) transposon system has been receiving much attention as a gene transfer method of choice since it allows permanent gene expression after insertion into the host chromosome. However, low transposition frequency in higher eukaryotes limits its use in commonly-used mammalian species. Researchers have therefore attempted to modify gene delivery and expression to overcome this limitation. In mouse liver, tumor induction using SB introduced by the hydrodynamic method has been successfully accomplished. Liver tumor in rat models using SB could also be of great use; however, dose of DNA, injection volume, rate of injection and achieving back pressure limit the use of the hydrodynamics-based gene delivery. In the present study, we combined the electroporation, a relatively simple and easy gene delivery method, with the SB transposon system and as a result successfully induced tumor in rat liver by directly injecting the c-Myc, HRAS and shp53 genes. The tumor phenotype was determined as a sarcomatoid carcinoma. To our knowledge, this is the first demonstration of induction of tumor in the rat liver using the electroporation-enhanced SB transposon system.


Assuntos
Elementos de DNA Transponíveis , Eletroporação , Neoplasias Hepáticas Experimentais/genética , Animais , Sequência de Bases , Primers do DNA , Feminino , Imuno-Histoquímica , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Masculino , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
16.
Biosci Biotechnol Biochem ; 77(3): 544-50, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23470751

RESUMO

This study investigated the anti-obesity effect of Adenophora triphylla root ethanol extract (ATREE). C57BL/6 mice were divided into five groups, a normal diet group (N), a control group fed only high-fat diet (HFD) (C), a positive control group fed HFD with 0.5% catechin (PC), and groups fed HFD with 0.5% (E1) or 1% (E2) ATREE. The body weight gain, hematological and serum biochemistry data, and anti-oxidative index in the liver and epididymal adipose tissue were improved significantly in the E group (E1, E2), as compared to the C group. As for histological findings, adipocyte size was reduced by ATREE. E group (E1, E2) showed significant increases in adiponectin, AMPK, and PPAR-α, and significant decreases in TNF-α, GPDH, and PPAR-γ, as compared to the C group. The above findings indicate that ATREE might have an anti-obesity effect through antioxidant and anti-inflammatory action. It is considered ATREE can be used as a natural treatment for obesity and metabolic syndrome induced by oxidative stress.


Assuntos
Campanulaceae/química , Dieta Hiperlipídica/efeitos adversos , Etanol/química , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Ração Animal , Animais , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico
17.
Int J Mol Med ; 30(2): 392-400, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22641502

RESUMO

Oxidative stress and oxidative photodamage induced by UV radiation can cause serious skin damage that is characterized by wrinkling, roughness, laxity and pigmentation. The effects of a sea buckthorn (Hippophae rhamnoides L.) fruit blend (SFB) containing sea buckthorn fruit extract, blueberry extract and collagen on UV-induced skin aging were examined by treating hairless mice for 6 weeks with UV irradiation and SFB administered orally. The effects of SFB were measured in the skin of these mice by phenotypical and histological analysis and western blotting. According to wrinkle formation analysis, the oral intake of SFB induced a decrease in wrinkle formation in the damaged skin of UV-irradiated mice. The thickness of the epidermis and dermis in the vitamin extracts (Vit)- and SFB-treated group was lower than that in the vehicle-treated group, but the group treated with SFB50 was the most effective group. The mice treated with the Vit- or SFB solution maintained a normal moisture content through the inhibition of transdermal water loss (TEWL) and an increase in skin moisture content. Furthermore, the levels of matrix metalloproteinase (MMP) and collagen protein expression were assessed in five groups to examine the mechanisms underlying the effects of SFB oral intake. The application of SFB induced a decrease in MMP-1 and -9 expression to the levels observed in the vehicle-treated group, but MMP-9 expression showed a much larger decrease than MMP-1. Furthermore, the expression of collagen-1 in the skin corresponded to MMP expression except for the SFB30-treated group, whereas the superoxide dismutase (SOD) activity was increased dramatically in the SFB50-treated group. These results suggest that SFB has potential as a protective and therapeutic drug candidate against skin aging that functions by regulating the moisture content, MMP expression levels and SOD activity.


Assuntos
Hippophae/química , Inibidores de Metaloproteinases de Matriz , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Superóxido Dismutase/metabolismo , Raios Ultravioleta/efeitos adversos , Administração Oral , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Misturas Complexas/administração & dosagem , Misturas Complexas/farmacologia , Derme/efeitos dos fármacos , Derme/metabolismo , Ativação Enzimática/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Frutas/química , Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Pelados , Envelhecimento da Pele/genética
18.
Korean J Hepatol ; 18(1): 48-55, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22511903

RESUMO

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC), which is the third most common cancer in Korea, has a very poor prognosis. However, only a few studies have performed a comprehensive survival-related analysis in all patients who were consecutively diagnosed and treated over a given period of time. The aim of this study was to determine the 5-year survival rate and its prognostic factors among HCC patients. METHODS: In total, 257 patients who were consecutively diagnosed with HCC between January 2000 and December 2003 were followed until death or until December 2008. We analyzed their survival outcomes according to their clinical characteristics, tumor staging, and treatment modalities, and determined the independent prognostic factors affecting survival. RESULTS: The patients were aged 59±10 years (mean±SD). During the follow-up period, 223 patients (86.8%) died and the overall median survival was 10.8 months; the 1-, 3-, and 5-year survival rates were 44.4%, 21.0%, and 12.1%, respectively. The outcomes in patients with tumor node metastasis (TNM) stage I or II and Child-Pugh class A or B were significantly better with surgical resection than with other treatment modalities (P<0.01). Patients who underwent supplementary transcatheter arterial chemoembolization as a second-line treatment after surgical resection had better outcomes than those who underwent surgical resection alone (P=0.02). Initial symptoms, Child-Pugh class, serum alpha-fetoprotein, tumor size, portal vein thrombosis, and TNM stage were found to be independent prognostic factors for survival among HCC patients. CONCLUSIONS: This retrospective cohort study elucidated survival outcomes and prognostic factors affecting survival in HCC patients at a single center.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Veia Porta , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Trombose Venosa/complicações , alfa-Fetoproteínas/análise
19.
Toxicol Lett ; 209(3): 255-63, 2012 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22245253

RESUMO

Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of radioisotope, (3)H-thymidine. However, there is also concern over compromised performance of non-radioisotopic LLNA, raising needs for additional endpoints to improve the accuracy. With the full 22 reference substances enlisted in OECD Test Guideline No. 429, we evaluated the performance of LLNA:BrdU-FCM along with the concomitant measurements of B/T cell ratio and ex vivo cytokine production from isolated lymph node cells (LNCs) to examine the utility of these markers as secondary endpoints. Mice (Balb/c, female) were topically treated with substances on both ears for 3 days and then, BrdU was intraperitoneally injected on day 5. After a day, lymph nodes were isolated and undergone FCM to determine BrdU incorporation and B/T cell sub-typing with B220+ and CD3e+. Ex vivo cytokine production by LNCs was measured such as IL-2, IL-4, IL-6, IL-12, IFN-γ, MCP-1, GM-CSF and TNFα. Mice treated with sensitizers showed preferential increases in B cell population and the selective production of IL-2, which matched well with the increases in BrdU incorporation. When compared with guinea pig or human data, BrdU incorporation, B cell increase and IL-2 production ex vivo could successfully identify sensitizers with the accuracy comparable to tLLNA, suggesting that these markers may be useful for improving the accuracy of LLNA:BrdU-FCM or as stand-alone non-radioisotopic endpoints.


Assuntos
Alérgenos , Linfócitos B/citologia , Citometria de Fluxo , Interleucina-2/biossíntese , Ensaio Local de Linfonodo , Linfonodos/imunologia , Alérgenos/imunologia , Alérgenos/farmacologia , Animais , Linfócitos B/imunologia , Bromodesoxiuridina/metabolismo , Células Cultivadas , Interpretação Estatística de Dados , Dermatite Alérgica de Contato , Determinação de Ponto Final , Ensaio de Imunoadsorção Enzimática , Feminino , Cobaias , Humanos , Interleucina-2/imunologia , Linfonodos/citologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Especificidade da Espécie , Linfócitos T/citologia , Linfócitos T/imunologia
20.
Regul Toxicol Pharmacol ; 59(2): 285-92, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21078356

RESUMO

Soy products are primarily composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. Recently, soy isoflavones with L-carnitine were reported to exhibit anti-obesity effects in mice. FCD, a combination of soybean extract and L-carnitine, is a newly developed food substance. As a part of its safety assessment, acute and 13-week subchronic toxicity studies were performed in a total of 100 Sprague-Dawley (SD) rats. In the acute study, a single limit dose of 2000 mg/kg was orally administered to five male and five female rats. No adverse effects or mortality was observed during a 14-day period or upon gross pathological examination. In the subchronic study, FCD was orally administered in daily doses of 500, 1000, and 2000 mg/kg for 13 weeks, resulting in no mortality, and no changes in hematological and serum biochemistry parameters, gross pathology or histopathology. However, body weights of females were significantly decreased 10 weeks after treatment at an average of 2000 mg/kg. In addition, a slight decrease in mean food and water consumption was observed at the same dose level for 13 weeks. Therefore, the no-observed-adverse-effect-level (NOAEL) of FCD was considered to be 2000 mg/kg for male and 1000 mg/kg for female SD rats.


Assuntos
Carnitina/toxicidade , Isoflavonas/toxicidade , Extratos Vegetais/toxicidade , Soja/química , beta-Glucanas/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Carnitina/administração & dosagem , Feminino , Isoflavonas/administração & dosagem , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , beta-Glucanas/administração & dosagem
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