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1.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1545-1557, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489033

RESUMO

An ultra-performance liquid chromatography(UPLC) method integrating characteristic chromatogram and eight terpenoids determination has been established for comparing the differences of Alismatis Rhizoma(Zexie) from different product areas. Thirty-seven batches of crude drugs and thirty batches of prepared slices of Alismatis Rhizoma were analyzed. The obtained data were analyzed by similarity evaluation, principal components analysis(PCA) and partial least squares discriminant analysis(PLS-DA). There were three main characteristic peaks in the characteristic chromatograms, and alisol B 23-acetate(S) was selected as the reference. Compared with the S peak, the relative retention times of the other two characteristic peaks were 0.55(alisol) and 0.77(alisol B), respectively. Peak areas and the ratio of alisol B to alisol B 23-acetate could be used to distinguish Alismatis Rhizoma from different geographical origins. The samples were divided into three groups by PCA and PLS-DA based on the content determination results, and they were "Jian Zexie"(Fujian and Jiangxi provinces), "Chuan Zexie"(Sichuan and Hubei provinces), and "Guang Zexie"(Guangxi province). The contents of chemical components in samples from different producing areas were notably different. For example, the contents of alisol A and alisol A 24-acetate were significantly higher in "Guang Zexie" compared with "Jian Zexie" and "Chuan Zexie"(P<0.000 1). The contents of alisol B and alisol C were significantly higher in "Chuan Zexie" compared with "Jian Zexie"(P<0.000 1). Combining the characteristic chromatograms and quantitative analysis of eight terpenoids, this study showed that the relative contents of components and their ratios were notable different in samples from different regions, but types and numbers of chemical compositions were basically similar. The results of this study illustrated the regional differences of Alismatis Rhizoma and their components characteristics, and provided references for authentication and quality control of Alismatis Rhizoma.


Assuntos
Rizoma , China , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Terpenos
2.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1566-1577, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489035

RESUMO

The present research was launched to improve the quality standards of Alismatis Rhizoma and supply scientific evidence and recommendations for the quality control of Alismatis Rhizoma in Chinese Pharmacopoeia(Ch. P) 2020 edition. The contents of water, total ash, heavy metals and deleterious element, pesticide residues and alcohol-soluble extract were analyzed according to the methods listed in the volume Ⅳ of Ch. P 2015 edition. Alisol B 23-acetate, alisol C 23-acetate and reference herbs were used to identify Alismatis Rhizoma by TLC method, which was developed by using a mixture of dichloromethane-methanol(15∶1) as developing solvent on silica gel GF_(254 )precoated plates. In HPLC method, alisol B 23-acetate and alisol C 23-acetate were separated with acetonitrile-water as the mobile phase and detected at 208 nm and 246 nm, respectively. Thirty-seven batches of crude drugs, thirty batches of prepared slices and nineteen batches of salt prepared slices of Alismatis Rhizoma were determined according to the methods established. The quality standards established based on the research results were specific and repeatable, and suitable for the quality evaluation of Alismatis Rhizoma. We recommended that the botanical sources, TLC examination, alcohol-soluble extract of salt prepared slices and content determination should be revised in the Ch. P 2020 edition.


Assuntos
Rizoma , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Controle de Qualidade
3.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1734-1744, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489056

RESUMO

In order to provide scientific recommendations for the revision of the quality standards of Poria in Chinese Pharmacopoeia(Ch. P) 2020 edition, a series of experiments were carried out to improve the quality standards of Poria. TLC methods were established to identify Poria by using pachymic acid, dehydrotumulosic acid and reference herbs as reference substances. The contents of water, total ash, pesticide residues, heavy metals and deleterious element, mycotoxins, sulfur dioxide residues and ethanol-soluble extract of herbal materials and decoction pieces of Poria were determined according to the methods recorded in the volume Ⅳ of Ch. P 2015 edition. An HPLC method was developed for the determination of pachymic acid and dehydropachymic acid. The contents of polysaccharide were determined by spectrophotometry using D-glucose as reference substance. The quality standards were established on the basis of the research results, in which the [assay] were added, and the [identification] and [tests] were revised when compared with Ch. P 2015 edition. The established methods are simple, specific, repeatable, and suitable for the quality evaluation of Poria.


Assuntos
Medicamentos de Ervas Chinesas , Poria , Cromatografia Líquida de Alta Pressão , Padrões de Referência
4.
5.
Front Oncol ; 9: 896, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552194

RESUMO

Background and Objective: Radiation-induced lymphopenia has a tangible impact on overall survival (OS) in multiple solid tumors. We investigated the association between circulating lymphocyte populations (CLPs) before and after stereotactic body radiation therapy (SBRT) and OS in patients with hepatocellular carcinoma (HCC). Materials and Methods: Seventy-eight HCC patients treated with SBRT between January 2013 and June 2017 were retrospectively analyzed. Baseline and post-treatment total peripheral lymphocyte counts (TPLCs) and values of different CLPs were obtained and analyzed for clinical outcomes. Univariate and multivariate Cox regression analyses were used to explore the independent prognostic factors for patient survival. Results: The one-, two- and three-year OS rates were 94.8, 75.9, and 63.3%, respectively. The mean TPLCs before and 10 days after SBRT were 1.4 × 109/L and 0.7 × 109/L, respectively. The TPLC recovered to its baseline value 1 year after SBRT. Multivariate analysis results revealed that variables, including tumor necrosis factor-alpha (TNF-α) level <5.5 ng/mL and post-treatment TPLC <0.45 × 109/L were independent factors for inferior OS. Further analysis showed that the values of CLPs, including CD3+, CD4+, CD8+, CD19+, and CD16+56+ cells dropped profoundly 10 days after SBRT, among which CD19+ B cell count was mostly depleted and gradually recovered after 2 months. Univariate analysis showed that both baseline and post-treatment TPLC and CLP (except post-treatment B cell) counts were significantly associated with patient OS (p < 0.05 for each). Further stratified analysis performed according to OS at 2 years demonstrated that the CD16+CD56+ NK cell counts remained significantly elevated in patients with better survival (OS > 2 years) compared to those in short-term survivors at 10 days, 1 month, and 2 months after SBRT (p < 0.05 for each). In addition, there were significant differences in TPLC and CD8+ T cell counts in patients with long-term and short-term OS at 2 months after SBRT (p < 0.05). Conclusions: Peripheral lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in HCC patients. Post-treatment lymphocyte subsets, including CD8+ T cell and NK cell counts were also associated with 2-year OS rates.

6.
Cancer Manag Res ; 11: 10929-10937, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32099457

RESUMO

Purpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT). Patients and methods: Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Results: The median follow-up was 36.9 (range: 4.1-73.5) months. Median PFS was 21.4 (range: 1.8-66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07-12.76, p=0.038) and OS (HR: 3.23; 95% CI: 1.01-9.11, p=0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients' poor prognosis (p<0.05 for each). Post-treatment increase in NLR ≥2.7-fold was shown to be a negative independent predictor of inferior OS (HR: 3.43; 95% CI: 1.14-10.38, p=0.029). Conclusion: High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC.

7.
Radiat Res ; 190(4): 385-395, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29979637

RESUMO

The goal of this study was to determine whether tetrandrine enhanced radiosensitization in different hepatocellular carcinoma cell lines and to elucidate the potential mechanism. We also tested whether PA28γ was regulated by tetrandrine. The human hepatocellular carcinoma cell lines HepG2 and LM3 were divided into six groups: control; low-dosage (0.5 or 5 µg/ml) tetrandrine alone; high-dosage (1.0 or 10 µg/ml) tetrandrine alone; irradiation alone; irradiation with low-dosage (0.5 µg/ml or 5 µg/ml) tetrandrine; and irradiation with high-dosage (1.0 µg/ml or 10 µg/ml) tetrandrine. Colony-forming assays were performed. Expression of cyclin and apoptosis-related proteins, including cyclin B1, phosphorylated cyclin-dependent kinase 1 [phospho-CDC2 (Tyr15)], Bax and caspase-3, as well as PA28γ expression, were evaluated using Western blot analysis. Apoptosis rate and cell cycle distribution were examined using flow cytometry analysis. Tetrandrine enhanced radiosensitivity in HepG2 and LM3 cells, as characterized by a narrower shoulder area and steeper linear area, and the enhanced radiosensitization increased with tetrandrine dosage. After tetrandrine treatment, the apoptosis rate significantly increased, whereas the proportion of cells in the G2 phase dramatically decreased in dose- and time-dependent manners after irradiation. However, the effect of reverse G2 arrest was weaker in p53-mutant cells (LM3 cells). Finally, we observed that tetrandrine downregulated PA28γ expression. Moreover, when PA28γ was downregulated, apoptosis and cell cycle distribution were also altered; however, the effects were weaker in p53-mutant cells. Therefore, we propose that tetrandrine-mediated apoptosis induction and G2 arrest attenuation are at least partly mediated by PA28γ.


Assuntos
Benzilisoquinolinas/farmacologia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Autoantígenos/metabolismo , Proteína Quinase CDC2/metabolismo , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Ciclina B1/metabolismo , Relação Dose-Resposta a Droga , Fase G2/efeitos dos fármacos , Fase G2/efeitos da radiação , Genes p53 , Humanos , Neoplasias Hepáticas/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína X Associada a bcl-2/metabolismo
8.
Sci Rep ; 8(1): 2264, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29396413

RESUMO

There is a growing consensus that genetic variation in candidate genes can influence cancer progression and treatment effects. In this study, we genotyped the rs9642880 G > T polymorphism using DNA isolated from blood samples of 271 hepatocellular carcinoma (HCC) patients who received radiotherapy treatment. We found that patients who carried the GT or TT genotypes had significantly shorter median survival times (MSTs) compared to patients with the GG genotype (14.6 vs.21.4 months). The multivariate P value was 0.027, the hazard ratio (HR) was 1.38, and the 95% confidence interval was 1.04-1.84. Further analysis revealed that patients with the variant genotypes had an increased risk of poor tumour response to radiotherapy (P = 0.036 and 0.002 for stable disease and progressive disease, respectively) and higher incidence of multiple intrahepatic lesions (P = 0.026) and BCLC C stage (P = 0.027). Moreover, further stratified survival analyses revealed that at least radioresponse and BCLC stage contributed to the association between the rs9642880 G > T polymorphism and survival of HCC patients in this study (P value, 0.017 vs 0.053 for BCLC C stage vs B stage; 0.011 vs 0.531 for radioresponse SD + PD vs CR + PR). These results illustrate the potential association between rs9642880 G > T and survival in HCC patients who received radiotherapy treatment.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Cromossomos Humanos 6-12 e X , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Sobrevida , Análise de Sobrevida , Resultado do Tratamento
9.
Zhongguo Zhong Yao Za Zhi ; 42(18): 3596-3601, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29218948

RESUMO

To screen potential biomarkers of curcumin related to treating depression rats by using metabolomics means, so as to explore the antidepressant action mechanism of curcumin. The healthy male SD rats were randomly divided into four groups. Chronic unpredictable mild stress (CUMS) stimulation was conducted for modeling for 2 weeks, and then curcumin (200 mg•kg⁻¹) or venlafaxine (40 mg•kg⁻¹) was given by gavage administration. The blank group and model group rats were given with the same volume of 1% CMCNa normal saline, once per day for two weeks. The rats serum for each group was collected and LC/MS-IT-TOF method was used to characterize the metabolic differences. Also multivariate statistical analysis was used to screen possible potential biomarkers and analyze the possible metabolic pathways. After administration of curcumin and venlafaxine respectively, the depression indexes of CUMS model rats were all improved significantly (P<0.05), but there were no significant differences between curcumin and venlafaxine groups. In PCA and PLS-DA analysis after curcumin or venlafaxine intervention on CUMS model group rats, the small molecule metabolites level reflects a normal trend, and particularly for the curcumin group. Through metabonomics technology, 11 biomarkers associated with curcumin antidepressant effect were screened, and at the same time seven metabolic pathways were involved. The results showed that curcumin had antidepressant effects, which was evident in both macro and micro levels, comparable with positive drug of venlafaxine. The antidepressant effect of curcumin may be associated with the glycerol phospholipid metabolism, linoleic acid metabolism, pentose and glucuronic acid ester and ether lipid metabolism, but still need further exploration in the future.


Assuntos
Antidepressivos/farmacologia , Biomarcadores , Curcumina/farmacologia , Depressão/tratamento farmacológico , Metabolômica , Animais , Modelos Animais de Doenças , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estresse Psicológico
10.
Zhongguo Zhong Yao Za Zhi ; 42(1): 119-124, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28945035

RESUMO

To explore the effect of the licorice-processed Tripterygium wilfordii on reducing the liver toxicity. In animal experiments, the liver toxicity of T. wilfordii was evaluated both before and after processing, and the differences in liver tissue biopsy, serum biochemical indexes and inflammatory cell factor among blank group, T. wilfordii group and licorice-processed T. wilfordii group were observed. Liver tissue biopsy results showed that liver tissue injury was obvious in T. wilfordii group, and no obvious injury was found in licorice-processed T. wilfordii group. As compared with the blank group, the levels of AST, ALT and CRE were significantly increased (P<0.01), UREA was increased (P<0.05), and ALB level was significantly decreased (P<0.01) in the T. wilfordii group. As compared with T. wilfordii group, the levels of AST, ALT, CRE, and UREA were decreased (P<0.01), while ALB was increased (P<0.01) in the licorice-processed T. wilfordii group. The results of inflammatory factors in rats showed that the levels of IL-1ß, IL-6, and TNF-α in T. wilfordii group were significantly higher than those in blank group (P<0.01); the levels of IL-1ß, IL-6, and TNF-α in licorice-processed T. wilfordii group were significantly lower than those in T. wilfordii group (P<0.01). Overall, licorice processing of T. wilfordii can effectively reduce the liver toxicity and reduce the liver injury caused by T. wilfordii. The experiment can provide reference for the clinical rational use of the T. wilfordii, and provide data support for the studies on reducing the liver toxicity of T. wilfordii by licorice processing.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glycyrrhiza/química , Fígado/efeitos dos fármacos , Tripterygium/toxicidade , Animais , Interleucina-1beta/sangue , Interleucina-6/sangue , Ratos , Fator de Necrose Tumoral alfa/sangue
11.
Oncotarget ; 7(52): 87246-87256, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27893432

RESUMO

Hepatocellular carcinoma (HCC) patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. We screened a microRNA (miRNA) microarray to identify potential serum biomarkers for BM in HCC patients. A miRNA microarray was used to screen for BM-related miRNAs in paired serum samples from HCC patients with BM and from HCC patients without BM. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to quantify candidate miRNAs in serum samples from 106 independent HCC patients. Levels of candidate miRNAs in tissue samples from an independent cohort of 296 HCC patients were evaluated by in situ hybridization and intratumoral tissue microarray. The migration and invasion capabilities of HCCLM3 and SMMC-7721 cells were evaluated following treatment with a mimic and an inhibitor of miR-34a. Ninety miRNAs were differentially expressed in sera from HCC patients with BM when compared with sera from non-BM HCC patients (P < 0.05). Only miR-34a and miR-498 had false discovery rates (FDRs) < 0.05. In cohorts of 106 and 296 HCC patients, we found that reduced serum and intratumoral miR-34a expression levels were independent risk factors for developing BM. Migration and invasion experiments indicated that a reverse correlation existed between miR-34a and HCC tumor migration and invasion. This study demonstrates the potential for the use of miR-34a as a serum and intratumoral tissue biomarker for predicting the risk of BM in HCC patients.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias Ósseas/etiologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , MicroRNAs/análise , MicroRNAs/sangue , Pessoa de Meia-Idade , Invasividade Neoplásica
12.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2915-2921, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28914037

RESUMO

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Tripterygium/toxicidade , Linhagem Celular , China , Humanos , Análise Espectral , Testes de Toxicidade , Tripterygium/química
13.
Oncotarget ; 7(3): 3587-98, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26657296

RESUMO

We developed an efficient microRNA (miRNA) model that could predict the risk of lymph node metastasis (LNM) in hepatocellular carcinoma (HCC). We first evaluated a training cohort of 192 HCC patients after hepatectomy and found five LNM associated predictive factors: vascular invasion, Barcelona Clinic Liver Cancer stage, miR-145, miR-31, and miR-92a. The five statistically independent factors were used to develop a predictive model. The predictive value of the miRNA-based model was confirmed in a validation cohort of 209 consecutive HCC patients. The prediction model was scored for LNM risk from 0 to 8. The cutoff value 4 was used to distinguish high-risk and low-risk groups. The model sensitivity and specificity was 69.6 and 80.2%, respectively, during 5 years in the validation cohort. And the area under the curve (AUC) for the miRNA-based prognostic model was 0.860. The 5-year positive and negative predictive values of the model in the validation cohort were 30.3 and 95.5%, respectively. Cox regression analysis revealed that the LNM hazard ratio of the high-risk versus low-risk groups was 11.751 (95% CI, 5.110-27.021; P < 0.001) in the validation cohort. In conclusion, the miRNA-based model is reliable and accurate for the early prediction of LNM in patients with HCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Modelos Estatísticos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Hibridização In Situ , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos
14.
Zhongguo Zhong Yao Za Zhi ; 40(19): 3851-8, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26975113

RESUMO

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.


Assuntos
Celastraceae/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Animais , Celastraceae/química , Celastraceae/toxicidade , Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/metabolismo , Fígado/metabolismo , Masculino , Espectrometria de Massas/métodos , Ratos , Ratos Sprague-Dawley
15.
Molecules ; 18(11): 13904-9, 2013 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-24284488

RESUMO

A new 15,16-dinorlabdane diterpenoid 1 and a known labdane diterpenoid 2, together with three known ergosterols 3-5, were isolated from the EtOAc-soluble portion of the EtOH extract of Leonurus japonicus. Their structures were elucidated by physical and spectroscopic analysis. Compound 1 showed in vitro coagulant activity in the APTT, PT, TT, and FIB assays.


Assuntos
Coagulantes/química , Diterpenos/química , Leonurus/química , Animais , Fibrinogênio/química , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Sprague-Dawley , Tempo de Trombina
16.
World J Gastrointest Oncol ; 4(1): 9-15, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22347534

RESUMO

AIM: To investigate the relationship between insulin receptor substrate-2 (IRS-2) G1057D polymorphism and the risk of gastric cancer (GC) in a Chinese population. METHODS: A case-control study with 197 GC patients and 156 age- and sex- matched control subjects was conducted. The genotypes of polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype frequencies of IRS-2 G1057D polymorphism in cases were obviously different from those in the control group (P = 0.031). Compared with GG genotype carriers, the risk for GC was significantly higher (adjusted odds ratio = 2.32, 95% CI: 1.03-5.23, P = 0.042) in the individuals with the IRS-2 DD genotype. Furthermore, stratified analysis was performed based on age, sex, smoking status and residence, but no significant difference between the two groups was found. In addition, no significant association between genotypes and clinicopathological features was observed either. CONCLUSION: This study demonstrates that IRS-2 G1057D is involved in susceptibility to GC, although further large-sample studies are still needed.

17.
World J Gastroenterol ; 17(23): 2860-6, 2011 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-21734795

RESUMO

AIM: To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer risk. METHODS: A hospital-based case-control study was conducted, including 307 gastric cancer patients and 307 age- and gender-matched control subjects. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The frequencies of the wild and variant genotypes in cases were significantly different from those of controls (P = 0.019). Compared with individuals with the wild genotype CC, subjects with the variant genotypes (CT + TT) had a significantly higher risk of gastric cancer (adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007). In stratified analyses, the elevated gastric cancer risk was especially evident in older individuals aged > 58 years, nonsmokers and rural subjects. Further analyses revealed that the variant genotypes were associated with poor tumor differentiation and adjacent organ invasion in the sub-analysis of gastric cancer patients. CONCLUSION: The ITGA2 gene C807T polymorphism may be associated with an increased risk of gastric cancer, differentiation and invasion of gastric cancer.


Assuntos
Predisposição Genética para Doença , Integrina alfa2/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Genótipo , Humanos , Fatores de Risco , Neoplasias Gástricas/patologia
18.
BMC Neurosci ; 11: 137, 2010 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-20969804

RESUMO

BACKGROUND: Neuron-derived neurotrophic factor (NDNF) is evolutionarily well conserved, being present in invertebrate animals such as the nematode, Caenorhabditis elegans, as well as in the fruit fly, Drosophila melanogaster. Multiple cysteines are conserved between species and secondary structure prediction shows that NDNF is mainly composed of beta-strands. In this study, we aimed to investigate the function of NDNF. RESULTS: NDNF is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF promoted migration and growth and elicited neurite outgrowth of mouse hippocampal neurons in culture. NDNF also protected cultured hippocampal neurons against excitotoxicity and amyloid beta-peptide toxicity. Western blotting showed that NDNF was exclusively expressed in the brain and spinal cord. Immunostaining indicated that NDNF was expressed by neurons and not by astrocytes. Cajal-Retzius cells, cortex neurons, hippocampus neurons, olfactory mitral cells, cerebellar purkinje cells, cerebellar granular cells and spinal neurons were found to be NDNF-positive. NDNF expression was observed in the neurons during development. CONCLUSIONS: The results of this study indicated that NDNF is a novel neurotrophic factor derived from neurons that may be useful in the treatment of neuronal degeneration diseases and nerve injuries.


Assuntos
Encéfalo/embriologia , Encéfalo/metabolismo , Diferenciação Celular/genética , Fatores de Crescimento Neural/biossíntese , Neurônios/metabolismo , Sequência de Aminoácidos , Animais , Anuros , Sequência de Bases , Encéfalo/crescimento & desenvolvimento , Bovinos , Diferenciação Celular/fisiologia , Células Cultivadas , Galinhas , Citoproteção/genética , Citoproteção/fisiologia , Drosophila , Regulação da Expressão Gênica no Desenvolvimento/genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Nematoides , Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/genética , Neurogênese/fisiologia , Neurônios/citologia , Ratos
19.
Cancer Biol Ther ; 9(3): 216-23, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20023382

RESUMO

CD133 has been identified as a cancer stem cell marker in colon and several other cancers, but its function is still unknown. We examined the CD133 expression in 44 human cancer cell lines, and found five of the 8 positive lines were from colon cancer. The CD133 positive subpopulation of colon cancer cells showed more vigorous growth and lower differentiation. Induction of differentiation reduced the CD133-positive population. Knockdown of CD133 expression in colon cancer cells could not induce cellular differentiation. Care must be taken if CD133 is used as the only marker of cancer stem cells in colon cancer, especially in established cell lines. CD133 negatively correlates with cell differentiation, but it is not a regulator of differentiation.


Assuntos
Antígenos CD/metabolismo , Diferenciação Celular , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Glicoproteínas/metabolismo , Peptídeos/metabolismo , Antígeno AC133 , Animais , Antígenos CD/genética , Western Blotting , Ciclo Celular , Ensaio de Unidades Formadoras de Colônias , Citometria de Fluxo , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/genética , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/antagonistas & inibidores , Peptídeos/genética , RNA Interferente Pequeno/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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