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2.
Climacteric ; 24(3): 253-260, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33084419

RESUMO

OBJECTIVES: Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disease with high morbidity and serious complications. Here, we studied the effect of glycyrrhizin on bone metabolism using the ovariectomized (OVX) mouse model. METHODS: Osteoclast-related gene expression and osteoclastic function were evaluated in RAW264.7 cells and bone marrow-derived monocytes (BMMs) by real-time polymerase chain reaction and bone resorption assay. For animal studies, female C57BL/6J mice were randomly divided into sham operated, OVX and OVX with glycyrrhizin groups. Bone mass and trabecular microarchitecture were analyzed by micro-computed tomography, dual X-ray absorptiometry, and histomorphometric analysis. Receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclastogenesis and the NF-κB signaling pathway were studied by tartrate-resistant acid phosphatase staining and western blotting, respectively. RESULTS: Glycyrrhizin inhibits RANKL-induced expression of Nfatc-1, c-Fos, Trap, Ds-stamp, and Ctsk in RAW264.7 cells. Also, fewer bone resorption pits form when BMMs are incubated in the presence of glycyrrhizin. Glycyrrhizin ameliorates bone loss and improves trabecular bone parameters in OVX mice. BMMs isolated from OVX mice show higher ability of RANKL-induced osteoclastogenesis, which is tremendously reversed by glycyrrhizin. There is significantly higher phosphorylation of IκB-α at Ser32 and NF-κB p65 at Ser536, as well as increased protein levels of c-FOS and NFATc-1 in BMMs of OVX mice, which are all greatly suppressed by glycyrrhizin. CONCLUSIONS: Our findings imply that glycyrrhizin is a potential efficient adjuvant therapeutic for PMO.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Ácido Glicirrízico/farmacologia , NF-kappa B/metabolismo , Osteoporose Pós-Menopausa/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Reabsorção Óssea/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/etiologia , Ovariectomia , Células RAW 264.7
3.
Zhonghua Yi Xue Za Zhi ; 100(23): 1783-1788, 2020 Jun 16.
Artigo em Chinês | MEDLINE | ID: mdl-32536123

RESUMO

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Cisplatino , Terapia Combinada , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Fluoruracila , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Diabet Med ; 34(4): 490-499, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27151271

RESUMO

AIMS: Metformin and acarbose have comparable efficacy as initial therapy for HbA1c reduction in Chinese patients with newly diagnosed Type 2 diabetes. However, not all participants achieved glycaemic control. Our aim was to discover a monotherapy predictor for therapeutic response in Type 2 diabetes on the basis of baseline features. METHODS: Data from the MARCH trial were collected, resulting in 698 individuals being available for longitudinal analyses. All participants were divided into subgroups based on successful and unsuccessful achievement of the glycaemic target according to primary endpoints at week 24 (HbA1c < 53 mmol/mol; 7.0%). Logistic regression analysis with stepwise variable selection was performed to assess the independent risk factors for good glycaemic control of monotherapy with metformin or acarbose. RESULTS: Median HbA1c was 66 ± 1 mmol/mol (8.2 ± 0.07%) in the metformin group at baseline, and 66 ± 1 mmol/mol (8.2 ± 0.07%) in the acarbose group. After 24 weeks of monotherapy, 79.8% of participants in the metformin group achieved glycaemic targets compared with 78.7% of those in the acarbose group. Multivariate regression analysis showed that BMI and fasting blood glucose were significant independent predictors for the maintenance of good glycaemic control in the metformin group, whereas phase I insulin secretion (Insulin/Glucose at 30 min, I30/G30) and duration of diabetes were associated with good glycaemic control in the acarbose group. CONCLUSIONS: For newly diagnosed Type 2 diabetes, some clinical features and laboratory parameters are important prognostic factors for predicting drug responsiveness. Participants with a higher BMI and lower fasting blood glucose achieved good glycaemic control when metformin was selected as the initial treatment. Acarbose was best for participants with higher phase I insulin secretion (I30/G30) and shorter duration of Type 2 diabetes.


Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Idoso , Povo Asiático , Glicemia/metabolismo , Índice de Massa Corporal , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sobrepeso/epidemiologia , Prognóstico , Resultado do Tratamento
5.
Oncogene ; 36(14): 1965-1977, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-27841868

RESUMO

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib therapy. It is therefore critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified a long non-coding RNA referred to as lncRNA-SRLR (sorafenib resistance-associated lncRNA in RCC) that is upregulated in intrinsically sorafenib-resistant RCCs. lncRNA-SRLR knockdown sensitized nonresponsive RCC cells to sorafenib treatment, whereas the overexpression of lncRNA-SRLR conferred sorafenib resistance to responsive RCC cells. Mechanistically, lncRNA-SRLR directly binds to NF-κB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance. A STAT3 inhibitor and IL-6-receptor antagonist both restored the response to sorafenib treatment. Moreover, a clinical investigation demonstrated that high levels of lncRNA-SRLR correlated with poor responses to sorafenib therapy in RCC patients. Collectively, lncRNA-SRLR may serve as not only a predictive biomarker for inherent sorafenib resistance but also as a therapeutic target to enhance responses to sorafenib in RCC patients.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Interleucina-6/metabolismo , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , RNA Longo não Codificante/fisiologia , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Análise em Microsséries , Niacinamida/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sorafenibe
6.
Genet Mol Res ; 15(3)2016 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-27706577

RESUMO

Bioactive oils extracted from sea buckthorn (Hippophae rhamnoides) berries contain highly nutritional and medicinal compounds; however, the oil contents of sea buckthorn berries are very low. Thirteen inter-simple sequence repeat (ISSR) primers were used to identify markers associated with oil content of dry pulp in 51 cultivars and lines, which clustered into three major groups based on 137 polymorphic markers. Dry pulp oil contents in 45 cultivars and lines in Group I ranged from 6.6 to 33.1%; these accessions belonged to H. rhamnoides ssp mongolica and its hybrids with H. rhamnoides ssp sinensis. Three lines (H. rhamnoides ssp mongolica) in Group II had high dry pulp oil contents (33.7 to 37.5%), whereas three lines of hybrids in Group III had low dry pulp oil contents (10.9 to 17.5%). The dry pulp oil content of H. rhamnoides ssp mongolica (27.2 ± 0.9%) was higher than that of hybrids (12.0 ± 1.2%) (P < 0.01). Four ISSR markers (881340, 8251000, 817380, and 8071100) had positive association with high dry pulp oil content (P < 0.01) using stepwise multiple regression analysis. The use of these ISSR markers is a potential strategy to select genotypes with high dry pulp oil content and suitable parental combinations for improvement of sea buckthorn berries.


Assuntos
Hippophae/genética , Hippophae/metabolismo , Óleos de Plantas/metabolismo , Biomarcadores/metabolismo , Ácidos Graxos/metabolismo , Repetições de Microssatélites
7.
Poult Sci ; 93(11): 2809-17, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25239530

RESUMO

An experiment was conducted to evaluate the effects of dietary α-lipoic acid (LA), acetyl-l-carnitine (ALC), and sex on antioxidative ability, energy, and lipid metabolism in broilers. A total of 972 one-day-old broilers with equal sex were randomly assigned in a 3 × 3 × 2 factorial design using 3 LA, 3 ALC levels, and 2 sexes (6 replications, 9 birds/replication). The LA and ALC levels were 0, 50, and 100 mg/kg, respectively. Results showed that increased LA or ALC resulted in increased total antioxidant capacity and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased levels of malondialdehyde in serum and liver of birds (P < 0.05). In addition, with increasing addition of LA or ALC, an increased (P < 0.01) level of insulin (Ins), as well as decreased (P < 0.05) levels of glucose and glucagon (Glu), were observed in serum of broilers. Total cholesterol and triglyceride (TG) levels decreased (P < 0.05) and nonesterified fatty acid, lipoprotein lipase, and lipase levels increased (P < 0.05) in serum with increased administration of LA or ALC. Moreover, a significant (P < 0.05) interaction of LA × ALC was observed for serum and liver SOD, serum GSH-Px, glucose, and TG levels. Birds fed diets containing 50 mg/kg of LA and 50 mg/kg of ALC had higher serum and liver SOD activities and lower serum glucose and TG levels than those fed diets containing 100 mg/kg of LA or ALC alone. The main effect of sex and all interactions among main effects (except LA × ALC) were not significant (P > 0.05) for all of the above parameters. Overall, the present data indicate that LA or ALC supplementation, or both, at low levels (50 or 100 mg/kg) improved antioxidative ability, energy metabolism, and lipid metabolism in broilers, and synergistic effects by the combined supplementation of LA and ALC were indicated by serum and liver SOD activities and serum glucose and TG levels.


Assuntos
Acetilcarnitina/metabolismo , Antioxidantes/metabolismo , Galinhas/metabolismo , Dieta/veterinária , Metabolismo Energético , Metabolismo dos Lipídeos , Ácido Tióctico/metabolismo , Ração Animal/análise , Animais , Suplementos Nutricionais/análise , Feminino , Masculino , Distribuição Aleatória , Fatores Sexuais
8.
Poult Sci ; 92(7): 1824-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23776270

RESUMO

A total of five hundred forty 19-wk-old HyLine Brown hens were used to study the long-term effects of increasing choline with 0 (control), 425, 850, 1,700, 3,400, and 6,800 mg/kg of corn-soybean meal-based diets on productive performance and egg quality. Phase 1 was from 19 to 58 wk, and phase 2 was from 59 to 68 wk. During the whole experimental period, dietary choline had no significant effects on feed intake, egg weight, and egg mass (P > 0.05). During phase 1, egg production decreased linearly (P < 0.05) and feed conversion ratio (FCR) tended to increase linearly (P = 0.057) with increasing choline level in the diet. Moreover, BW decreased both linearly (P < 0.01) and quadratically (P < 0.05) as choline increased from 0 to 6,800 mg/kg. No significant treatment effects were found for shell thickness and shell strength of eggs (P > 0.05). However, albumen height and Haugh units increased linearly (P < 0.01 and P < 0.05, respectively) as choline increased during phase 2. Compared with the control group, diets supplemented with 425 or 850 mg of choline/kg significantly (P < 0.01) improved yolk color during phase 1. This study indicates that a dietary choline level of no more than 700 mg/kg is sufficient to maintain egg production. The effect of choline on egg quality was minimal when hens were fed a corn-soybean meal-based diet from 19 to 68 wk of age.


Assuntos
Galinhas , Colina/farmacologia , Ovos/normas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Colina/administração & dosagem , Dieta/veterinária , Esquema de Medicação , Feminino , Pigmentos Biológicos
9.
Genet Mol Res ; 12(2): 1143-54, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23661439

RESUMO

The blood cockle, Tegillarca granosa, is a widely consumed clam in the Indo-Pacific region. Glutamine synthetase (GS) is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine. We identified the GS of T. granosa (Tg-GS) from hemocytes by 3'- and 5'-rapid amplification of cDNA ends (RACE)-PCR. The full-length cDNA consisted of 1762 bp, with a 1104-bp open reading frame encoding 367 amino acids. Sequence comparison showed that Tg-GS has homology to GS of other organisms, with 79.78% identity with GS from the Pacific oyster Crassostrea gigas, 71.98% identity with GS from the zebrafish Danio rerio, and 68.96% identity with human Homo sapiens GS. A C-beta-Grasp domain and an N-catalytic domain were identified in Tg-GS, indicating that Tg-GS should be classified as a new member of the GS family. A quantitative RT-PCR assay was used to detect mRNA expression of Tg-GS in five different tissues. Higher levels of mRNA expression of GS were detected in the tissues of hemocytes and the mantle. Up-regulation of GS by challenge with the bacteria Vibrio parahaemolyticus and with bacterial wall lipopolysaccharides showed that GS plays a role in anti-bacterial immunity. We conclude that pathogen infection significantly induces expression level of Tg- GS, and that activation of GS influences the immune response of T. granosa by increasing glutamine concentration.


Assuntos
Arcidae/genética , Arcidae/metabolismo , Glutamato-Amônia Ligase/genética , Hemócitos/imunologia , Hemócitos/metabolismo , Lipopolissacarídeos/imunologia , Vibrio parahaemolyticus/imunologia , Sequência de Aminoácidos , Animais , Arcidae/microbiologia , Sequência de Bases , DNA Complementar , Etiquetas de Sequências Expressas , Feminino , Expressão Gênica , Biblioteca Gênica , Glutamato-Amônia Ligase/classificação , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência
10.
Br J Dermatol ; 167(6): 1374-81, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22897348

RESUMO

BACKGROUND: Psoriasis is associated with poor health-related quality of life, including sleep impairment. OBJECTIVE: To assess the extent of sleep impairment, the effect of adalimumab on sleep and other patient-reported outcomes, and correlations between changes in these outcomes and sleep quality in patients with psoriasis. METHODS: Patients in the 16-week, open-label, Phase IIIb PROGRESS trial had chronic plaque psoriasis and suboptimal response to prior therapy (etanercept, methotrexate or narrowband ultraviolet B phototherapy). Adalimumab was self-injected subcutaneously (80 mg at week 0, then 40 mg every other week from week 1). The focus for this analysis was the Medical Outcomes Study Sleep Scale. Other patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), Physician's Global Assessment, a visual analogue scale for psoriasis/psoriatic arthritis (PsA) pain, and the Work Productivity and Activity Index Questionnaire-Specific Health Problems. RESULTS: Patients with psoriasis had impaired sleep at baseline. The degree of sleep impairment was significantly associated with the extent of work productivity for all sleep measures and, for some sleep measures, was associated with DLQI impairment, clinical severity measured by PASI, the presence of PsA, and depression. Adalimumab treatment significantly improved sleep quality by 15% from baseline, as well as DLQI score, pain and work productivity. The improvement in sleep was partially explained (R(2 ) = 0·16, P < 0·001) by improvements in the objectively measured psoriasis signs in PASI. CONCLUSIONS: Adalimumab treatment improved sleep outcomes and other patient-reported outcomes including health-related quality of life, work productivity, daily activity and disease-related pain.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Psoríase/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Absenteísmo , Adalimumab , Adulto , Substituição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/fisiopatologia , Inquéritos e Questionários , Resultado do Tratamento , Trabalho
11.
Br Poult Sci ; 51(1): 109-17, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20390575

RESUMO

1. The aim of the present study was to demonstrate trace mineral interactions among organic copper, iron, manganese and zinc (Cu, Fe, Mn and Zn) in broiler chickens. 2. Three experiments were conducted using a control diet which was deficient in Cu, Fe, Mn and Zn. 3. In experiment 1, the control diet, supplemental organic Cu, Fe alone and combined diets, were randomly fed to 4 groups of one-day-old Cobb broilers (each group had 6 replicates of 4 birds). 4. In experiment 2, the control diet, supplemental organic Mn and Zn alone or combined with Cu, Fe diets and corresponding inorganic combined diet, were randomly fed to 6 groups (each group had 8 replicates of 6 birds). 5. In experiment 3, the depletion of organic Zn, the depletion of inorganic Zn and normal Zn treatments were carried out in three groups of one-day-old Cobb broilers (each group had 8 replicates of 6 birds). 6. Adding organic Cu, Fe and Mn alone or combined to Zn deficient diets did not significantly improve bird performance and were mostly excreted. Supplemental organic Zn alone or combined with other elements significantly increased feed intake, body weight gain and tibia bone length. However, supplemental organic Fe alone or combined with Cu significantly increased feed intake but had no obvious effect on body weight gain. The organic Fe supplementation resulted in a wider tibia. 7. Depletion of organic and inorganic Zn resulted in decreased feed intake, body weight gain and total tibia bone Zn content. Zinc deficiency did not affect the uptake of organic Fe by tibia bone but reduced its total Fe content. 8. Zinc is the first limiting element among these 4 trace minerals. Adding Mn, Cu and Fe to Zn deficient diets did not stimulate bird performance. Surplus organic Fe and Cu resulted in increased feed intake and increased tibia bone Fe content but did not contribute to bird performance.


Assuntos
Peso Corporal/fisiologia , Galinhas/crescimento & desenvolvimento , Oligoelementos/metabolismo , Animais , Galinhas/metabolismo , Cobre/metabolismo , Ingestão de Alimentos/fisiologia , Ferro/metabolismo , Masculino , Manganês/metabolismo , Distribuição Aleatória , Tíbia/anatomia & histologia , Zinco/metabolismo
12.
Br Poult Sci ; 50(1): 95-102, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19234934

RESUMO

1. The aim of the present study was to determine the optimal content of organically complexed zinc (Zn) for broiler chickens. 2. Five different Zn and manganese (Mn) dietary contents from organically complexed supplements including a control diet containing 15 mg Mn and 20 mg Zn/kg diet, were randomly fed to one-day-old Cobb broilers (each treatment had 6 replicates of 4 birds) for 35 d. Body weight and feed intake were recorded weekly. At the end of the experiment, two birds from each cage were killed and their right tibia were collected to measure bone size, strength and mineral contents. 3. Body weight gain and total tibia copper (Cu), iron (Fe), Mn and Zn contents increased linearly with supplemental Zn and Mn intake. The optimal Zn requirements for broilers at 1-14 and 14-35 d of age were 58 and 68 mg/kg diet, respectively. 4. Supplementation of Mn and Zn had no effect on tibia bone width and strength, but increased tibia length. 5. In commercial practice, organically complexed Zn may need to be supplemented during the entire period of production at a higher content than NRC recommendation but it is not necessary to exceed 70 mg/kg diet.


Assuntos
Galinhas/crescimento & desenvolvimento , Compostos Organometálicos/administração & dosagem , Zinco/administração & dosagem , Ração Animal , Animais , Peso Corporal/fisiologia , Galinhas/metabolismo , Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Fezes/química , Masculino , Manganês/administração & dosagem , Distribuição Aleatória , Análise de Regressão , Tíbia/química , Tíbia/metabolismo
13.
Neoplasma ; 53(6): 463-70, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17167713

RESUMO

The aim of presented study was to further investigate the concentration-dependent changes induced by isothiocyanate iberin (IBN) in human colon carcinoma Caco-2 cells. The concentrations of IBN below IC(50) value (18 microM, 72 h) triggered the augmentation of mRNA levels for phase II detoxification GSTA1 and UGT1A1 enzymes and antioxidant thioredoxin reductase 1 gene in cells treated for 24 h. In addition a significant increase of acetylated H4 histone was detected. The mRNA induction peaked at IC(50) value and returned to level of control cells at 40 microM concentration of IBN. The cell cycle changes, gamma-H2AX stainability and the increase of phospho-H3 mitotic marker were induced at concentrations above IC(50) value. Appearance of Annexin V positive apoptotic cells and sub-G1 fragmented DNA as well as decrease of mitochondrial transmembrane potential confirmed cytotoxic effect of IBN observed in MTT assay. The predominance of necrotic cells and profound positivity of gamma-H2AX took place at the highest concentration of IBN. Thus, IBN represents the effective member of natural chemopreventive isothiocyanate family with which apoptotic potential can by employed to eliminate tumor cells.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Glutationa Transferase/metabolismo , Histonas/metabolismo , Isotiocianatos/farmacologia , Extratos Vegetais/farmacologia , Processamento de Proteína Pós-Traducional , Acetilação , Células CACO-2/patologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Citometria de Fluxo , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tiorredoxina Redutase 1 , Tiorredoxina Dissulfeto Redutase/genética , Tiorredoxina Dissulfeto Redutase/metabolismo
14.
Food Chem Toxicol ; 44(10): 1659-66, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16806628

RESUMO

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia (A.) oxyphylla, showed antioxidant neuroprotective effect in our previous study. Here, we investigated the effect of PCA on the MPP(+)-induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. The apoptosis in MPP(+)-induced PC12 cells was associated with loss of mitochondrial membrane potential, the formation of reactive oxygen species (ROS), GSH depletion, activation of caspase-3 and down-regulation of Bcl-2. In contrast, treatment of PC12 cells with PCA significantly prevented the above-mentioned mitochondrial dysfunction. Our data pointed to the potential clinical application/use of PCA to overcome neurodegenerative diseases such as Parkinson's disease.


Assuntos
1-Metil-4-fenilpiridínio/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-fenilpiridínio/toxicidade , Alpinia/química , Animais , Caspase 3 , Caspases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ativação Enzimática , Glutationa/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/fisiologia , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Food Chem Toxicol ; 44(3): 436-43, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16223555

RESUMO

An ethyl acetate extract of Alpinia oxyphylla was found to possess neuroprotective activity against 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apotosis and oxidative stress in cultured PC12 cells. From the extract, a phenolic compound was isolated through bioassay-guided fractionation and identified as protocatechuic acid (PCA) by IR, MS, and (1)H and (13)C NMR spectroscopy. It was the first time which was isolated from the kernels of A. oxyphylla. Exposure of PC12 cells to 1mM MPP(+) may cause significant viability loss and apoptotic cell death. PCA stimulated PC12 cellular proliferation and markedly attenuated MPP(+)-induced apoptotic cell death in a dose-dependent manner. By observing the nuclear morphological changes and flow cytometric analysis, PCA showed its significant effect on protecting PC12 cells against MPP(+)-induced apoptosis. Meanwhile, PCA enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in PC12 cells. In addition, PCA also dose-dependently reduced the hydrogen peroxide (H(2)O(2))- or sodium nitroprusside (SNP)-induced cell death in PC12 cells. The results suggest that PCA may be one of the primary active components in the kernels of A. oxyphylla and provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease.


Assuntos
Alpinia/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-fenilpiridínio/toxicidade , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Peróxido de Hidrogênio , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Extratos Vegetais/farmacologia , Ratos , Superóxido Dismutase/metabolismo
16.
Toxicon ; 43(1): 53-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15037029

RESUMO

In the present study, using a rat pheochromocytoma (PC12) cell line, the effect of catalpol on H2O2-induced apoptosis was studied. The apoptosis in H2O2-induced PC12 cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, the release of mitochondrial cytochrome c to cytosol and sequential activation of caspase-1 and caspase-3 then leading to cleavage of poly-ADP-ribose polymerase (PARP). Catalpol not only suppressed the down-regulation of Bcl-2, up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol, but also attenuated caspase-3 activation, PARP cleavage, and eventually protected against H2O2-induced apoptosis. Taken together, these results suggest that treatment of PC12 cells with catalpol can block H2O2-induced apoptosis by the regulation of Bcl-2 family members, as well as suppression of cytochrome c release and caspase cascade activation.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/efeitos dos fármacos , Citocromos c/efeitos dos fármacos , Glucosídeos/farmacologia , Iridoides/farmacologia , Células PC12/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2 , Animais , Apoptose/genética , Caspases/genética , Caspases/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica , Genes bcl-2/efeitos dos fármacos , Peróxido de Hidrogênio , Glucosídeos Iridoides , Células PC12/metabolismo , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética , Ratos , Proteína X Associada a bcl-2
17.
Biofactors ; 15(1): 27-38, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11673642

RESUMO

A novel selenium form, nano red elemental selenium (Nano-Se) was prepared by adding bovine serum albumin to the redox system of selenite and glutathione. Nano-Se has a 7-fold lower acute toxicity than sodium selenite in mice (LD(50) 113 and 15 mg Se/kg body weight respectively). In Se-deficient rat, both Nano-Se and selenite can increase tissue selenium and GPx activity. The biological activities of Nano-Se and selenite were compared in terms of cell proliferation, enzyme induction and protection against free racial-mediated damage in human hepatoma HepG2 cells. Nano-Se and selenite are similarly cell growth inhibited and stimulated synthesis of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase (TR). When HepG2 cells were co-treated with selenium and glutathione, Nano-Se showed less pro-oxidative effects than selenite, as measured by cell growth. These results demonstrate that Nano-Se has a similar bioavailability in the rat and antioxidant effects on cells.


Assuntos
Selênio/farmacologia , Disponibilidade Biológica , Carcinoma Hepatocelular , Morte Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Radicais Livres , Glutationa/farmacologia , Glutationa Peroxidase/biossíntese , Glutationa Peroxidase/metabolismo , Inibidores do Crescimento/farmacologia , Humanos , Cinética , Neoplasias Hepáticas , Paraquat/farmacologia , Selênio/deficiência , Selênio/farmacocinética , Selênio/toxicidade , Selenito de Sódio/toxicidade , Tiorredoxina Dissulfeto Redutase/biossíntese , Células Tumorais Cultivadas
18.
Chem Pharm Bull (Tokyo) ; 49(7): 795-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11456082

RESUMO

The ginsenoside-beta-glucosidase that hydrolyzes the beta-(1-->2)-glucoside of the ginsenoside Rg3 sugar moiety to ginsenoside Rh2 was isolated from the ginseng root, and the enzyme was purified and characterized. The enzyme was purified to one spot in SDS polyacrylamide gel electrophoresis, and its molecular weight was about 59 kDa. The optimum temperature of the ginsenoside-beta-glucosidase was 60 degrees C, and the optimum pH was 5.0. Ca2+ ion had positive effect on ginsenoside-beta-glucosidase, while Cu2+ had negative effect on it. The ginsenoside-beta-glucosidase may be a special beta-glucosidase that is different from the original exocellulase such as beta-glucosidase (EC 3.2.1.21).


Assuntos
Panax/enzimologia , beta-Glucosidase/síntese química , Cromatografia DEAE-Celulose , Cromatografia em Camada Fina , Ginsenosídeos , Hidrólise , Peso Molecular , Extratos Vegetais/análise , Proteínas de Plantas/análise , Saponinas/química , beta-Glucosidase/isolamento & purificação
19.
Zhong Yao Cai ; 24(11): 823-5, 2001 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15575169

RESUMO

By herbalogical study and investigation, "lideri" used by Mongolia doctors in different areas mainly contains 10 species from 4 genera of 4 families, but the quality materials only contains 3 species, Tinospora sinensis (Lour.) Merr., T. cordifolia Miers and T. capillipes Gagnep.


Assuntos
Medicina Tradicional da Mongólia , Extratos Vegetais/química , Tinospora/química , Medicina Herbária , Extratos Vegetais/classificação , Tinospora/classificação
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 21(3): 193-5, 2001 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12577336

RESUMO

OBJECTIVE: To explore the therapeutic mechanism of Kangzhen Zhijing Capsule (KZZJC) on rats with Parkinson's disease (PD). METHODS: PD rat model was established by microinjection of 6-hydroxydopamine solution into left substantia nigra zona compacta (SNZC). Model rats were randomly divided into 3 groups and treated with KZZJC, levodopa and normal saline respectively for 30 days. The rotational behavior of rats before and after treatment was observed. Then rats were sacrificed and relevant indexes of left SNZC and striatum were examined. RESULTS: In rats treated with KZZJC, the rotational behavior was improved (P < 0.05), the levels of dopamine (DA) content and DA/homovanillic acid (HVA) ratio in striatum, and glutathione peroxidase, superoxide dismutase and glutathione in SNZC increased, but malondialdehyde in SNZC decreased, as compared with those in rats treated with normal saline, the difference was significant (P < 0.01 or P < 0.05). Rotational behavior in rats treated by levodopa was improved significantly (P < 0.01). CONCLUSION: KZZJC could partially improve the rotational behavior in PD model rats, increase DA content and DA/HVA ratio in striatum. The mechanism might be the reducing of free radical damage and DA catabolism.


Assuntos
Antiparkinsonianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Animais , Dopamina/metabolismo , Glutationa Peroxidase/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Microinjeções , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rotação , Superóxido Dismutase/metabolismo
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