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1.
Int J Radiat Oncol Biol Phys ; 105(1): 124-131, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075310

RESUMO

PURPOSE: To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI. METHODS AND MATERIALS: A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis. RESULTS: Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D2) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D2) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D2). CONCLUSIONS: In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D2) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.

2.
Leukemia ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

3.
Arthritis Rheumatol ; 70(11): 1745-1756, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29750395

RESUMO

OBJECTIVE: It has been reported that ADAMTS-12 is a susceptibility gene for rheumatoid arthritis (RA) development, and its level is significantly increased in RA patients. In addition, ADAMTS-12 is reported to be required for inflammation in otherwise healthy subjects. This study was undertaken to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. METHODS: The collagen-induced arthritis (CIA) model was established in ADAMTS-12-deficient mice and their control littermates to determine the role of ADAMTS-12 in vivo. Micro-computed tomography scanning was used to demonstrate the destruction of the ankle joint; histologic analysis illustrated synovitis, pannus formation, and bone and cartilage destruction; enzyme-linked immunosorbent assay was performed to measure serum levels of inflammatory cytokines; and protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 and its various deletion mutants with connective tissue growth factor (CTGF). RESULTS: Deficiency of ADAMTS-12 led to accelerated inflammatory arthritis in the CIA mouse model. Loss of ADAMTS-12 caused enhanced osteoclastogenesis. In vitro and in vivo protein-protein interaction assays demonstrated that ADAMTS-12 bound and processed CTGF, a previously unrecognized substrate of ADAMTS-12. In addition, deletion of ADAMTS-12 enhanced, while overexpression of ADMATS-12 reduced, CTGF-mediated inflammation. Furthermore, ADAMTS-12 regulation of inflammation was largely lost in CTGF-deficient macrophages. Importantly, blocking of CTGF attenuated elevated inflammatory arthritis seen in the ADAMTS-12-deficient CIA mouse model. CONCLUSION: This study provides evidence that ADAMTS-12 is a critical regulator of inflammatory arthritis and that this is mediated, at least in part, through control of CTGF turnover.

4.
Int J Equity Health ; 17(1): 40, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609601

RESUMO

BACKGROUND: Per United Nations' Sustainable Development Goals, Nepal is aspiring to achieve universal and equitable access to safe and affordable drinking water and provide access to adequate and equitable sanitation for all by 2030. For these goals to be accomplished, it is important to understand the country's geographical heterogeneity and inequality of access to its drinking-water supply and sanitation (WSS) so that resource allocation and disease control can be optimized. We aimed 1) to estimate spatial heterogeneity of access to improved WSS among the overall Nepalese population at a high resolution; 2) to explore inequality within and between relevant Nepalese administrative levels; and 3) to identify the specific administrative areas in greatest need of policy attention. METHODS: We extracted cluster-sample data on the use of the water supply and sanitation that included 10,826 surveyed households from the 2011 Nepal Demographic and Health Survey, then used a Gaussian kernel density estimation with adaptive bandwidths to estimate the distribution of access to improved WSS conditions over a grid at 1 × 1 km. The Gini coefficient was calculated for the measurement of inequality in the distribution of improved WSS; the Theil L measure and Theil T index were applied to account for the decomposition of inequality. RESULTS: 57% of Nepalese had access to improved sanitation (range: 18.1% in Mahottari to 100% in Kathmandu) and 92% to drinking-water (range: 41.7% in Doti to 100% in Bara). The most unequal districts in Gini coefficient among improved sanitation were Saptari, Sindhuli, Banke, Bajura and Achham (range: 0.276 to 0.316); and Sankhuwasabha, Arghakhanchi, Gulmi, Bhojpur, Kathmandu (range: 0.110 to 0.137) among improved drinking-water. Both the Theil L and Theil T showed that within-province inequality was substantially greater than between-province inequality; while within-district inequality was less than between-district inequality. The inequality of several districts was higher than what is calculated by regression of the Gini coefficient and our estimates. CONCLUSIONS: This study showed considerable geographical heterogeneity and inequality not evidenced in previous national statistics. Our findings may be useful in prioritizing resources to reduce inequality and expand the coverage of improved water supply and sanitation in Nepal.


Assuntos
Água Potável , Equidade em Saúde/estatística & dados numéricos , Saneamento/estatística & dados numéricos , Abastecimento de Água/estatística & dados numéricos , Demografia , Geografia , Humanos , Nepal , Fatores Socioeconômicos
5.
Ying Yong Sheng Tai Xue Bao ; 29(1): 269-277, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29692036

RESUMO

As a unique hydrological characteristic, the tidal action can strongly affect carbon balance in a salt marsh despite their short duration. Using the eddy covariance technique, we measured the net ecosystem CO2 exchange (NEE) and its environmental factors and tidal change over a salt marsh in the Yellow River Delta. It aimed to investigate the effect of tidal process and drying and wetting cycles induced by tides on NEE. The results showed that the tidal process promoted the daytime CO2 uptake, but it didn't clearly affect the nighttime CO2 release. Tidal inundation was a major factor influencing daytime NEE. The diurnal change of NEE showed a distinct U-shaped curve on both drought and wet stages, but not with substantial variation in its amplitude during the drought stage. The drying and wetting cycles enhanced the absorption of daytime CO2. Under drought stage, the mean of the maximum photosynthetic rate (Amax), apparent quantum yield (α) and ecosystem respiration (Reco) were higher than those in wet stage. In addition, the drying and wetting cycles suppressed the nighttime CO2 release from the salt marsh but increased its temperature sensitivity.


Assuntos
Dióxido de Carbono , Ecossistema , Áreas Alagadas , China , Rios , Ondas de Maré
6.
J Cancer ; 9(6): 1025-1032, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581782

RESUMO

Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

7.
Cell Stem Cell ; 22(2): 177-190.e7, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29395054

RESUMO

The development of cell therapy for repairing damaged or diseased skeletal muscle has been hindered by the inability to significantly expand immature, transplantable myogenic stem cells (MuSCs) in culture. To overcome this limitation, a deeper understanding of the mechanisms regulating the transition between activated, proliferating MuSCs and differentiation-primed, poorly engrafting progenitors is needed. Here, we show that methyltransferase Setd7 facilitates such transition by regulating the nuclear accumulation of ß-catenin in proliferating MuSCs. Genetic or pharmacological inhibition of Setd7 promotes in vitro expansion of MuSCs and increases the yield of primary myogenic cell cultures. Upon transplantation, both mouse and human MuSCs expanded with a Setd7 small-molecule inhibitor are better able to repopulate the satellite cell niche, and treated mouse MuSCs show enhanced therapeutic potential in preclinical models of muscular dystrophy. Thus, Setd7 inhibition may help bypass a key obstacle in the translation of cell therapy for muscle disease.

8.
Int J Low Extrem Wounds ; 16(3): 154-162, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28741388

RESUMO

Traditional Chinese medicine has great potential to improve wound healing. ANBP, the mixture of 4 Chinese herbs- Agrimoniapilosa, Nelumbonucifera, Boswelliacarteri, and Pollen typhae-is effective in trauma treatment while its mechanism is still elusive. In this study, quantitative proteomics and bioinformatics analyses were performed to decipher the possible roles of ANBP in accelerated wound healing of mouse skin. Among all 3171 identified proteins, 90, 71, 80, and 140 proteins were found to be differently expressed in 6 hours, 3 days, 7 days, and 14 days ANBP-treated tissues compared with corresponding control tissues, respectively. The result showed that different biological processes and pathways were activated at different healing stages. At the early healing stage, ANBP treatment mainly affected several biological processes, including immune and defense response, vascular system restoration, hemostasis and coagulation regulation, lipid metabolism and signal transduction, while muscle tissue, hair, epidermis, extracellular matrix and tissue remodeling related activities were the major events in ANBP promoted later wound healing. This is the first quantitative proteome study of ANBP-treated wound tissues, which provide a new perspective for the mechanism of ANBP accelerated wound healing and is of guiding significance for clinical application of ANBP in trauma disorders cure.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteômica , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/patologia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Pele/efeitos dos fármacos , Pele/patologia , Cicatrização/genética , Ferimentos e Lesões/genética
9.
Zhongguo Zhong Yao Za Zhi ; 41(1): 83-86, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28845645

RESUMO

Eight compounds were isolated from the 50% ethanol extract of Impatiens pritzllii var.hupehensis through various column chromatography methods including silica gel, Sephadex LH-20, and preparative HPLC. Their structures were elucidated as 2,6-dimethyl-2-vinyl-2,3,4,7-tetrahydrooxepine(1), 1,3,6-trihydroxy-7-methyl-anthraquinone(2),4-hydroxybenzaldehyde(3),4-(3-methoxy-4-hydroxyphenyl)-2-butanone(4), podophyllotoxin(5),scopoletin(6), α-spinasterol(7) and 3-O-ß-D-glucopyranosyl-α-spinasterol(8) based on the NMR and MS spectral data. Compound 1 is new compound and compounds 2-8 are isolated from this plant for the first time.


Assuntos
Medicamentos de Ervas Chinesas/química , Impatiens/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
10.
Pak J Pharm Sci ; 28(6): 2191-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26639511

RESUMO

The extraction, fractionation and recognition of flavonoids from the ethanolic extract of young twigs and leaves of C. bonduc were carried out. In addition, cytotoxic study of the flavonoids on two cancer cell lines, BGC-823 and HeLa was carried our using sulphorhodamine B assay. Seven flavonoids, six of which are being reported for the first time in this plant, were isolated. Their structures were identified by MS and NMR spectroscopic methods. Petroleum ether, ethyl acetate and water fractions exhibited moderate cytotoxic activity against HeLa cells. Five compounds showed cytotoxic activity against HeLa cell in comparison with Paclitaxel, while only one compound showed a good degree of cytotoxic activity against BGC-823 cell in comparison to Paclitaxel. The results obtained showed a structure - activity relationship.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Caesalpinia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta , Antineoplásicos Fitogênicos/isolamento & purificação , Caesalpinia/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Flavonoides/isolamento & purificação , Células HeLa , Humanos , Concentração Inibidora 50 , Espectrometria de Massas , Estrutura Molecular , Paclitaxel/farmacologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química , Plantas Medicinais , Espectroscopia de Prótons por Ressonância Magnética , Solventes/química , Relação Estrutura-Atividade
11.
Yao Xue Xue Bao ; 50(4): 475-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26223131

RESUMO

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.


Assuntos
Folhas de Planta/química , Caules de Planta/química , Rutaceae/química , Cromatografia Líquida de Alta Pressão , Sesquiterpenos/isolamento & purificação
12.
Int J Low Extrem Wounds ; 14(4): 335-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25795279

RESUMO

Wound healing is a troublesome problem in diabetic patients. Besides, there is also an increased risk of postsurgical wound complications for diabetic patient. It has been revealed that traditional Chinese medicine may promote healing and inhibit scar formation, while the changes of morphology and physiology of wounds on such medicine treatment still remain elusive. In this study, we first used the ultralow temperature preparation method to produce mixed superfine powder from Agrimonia pilosa (A), Nelumbo nucifera (N), Boswellia carteri (B), and Pollen typhae (P), named as ANBP. Applying ANBP on 40 streptozotocin (STZ)-induced diabetic C57BL/6 mice (4-6 weeks, 20 ± 2 g), we observed that the wound healing process was accelerated and the wound healing time was shortened (14 days, P < .05). Pathological observation using hematoxylin-eosin staining indicated that inflammatory cells were reduced (P < .05) while the thickness of granulation tissue and length of epithelial tongue were increased (P < .05). The vascular density was increased on 7 and 14 days after ANBP treatment. Masson and Sirius red staining showed that, at the early stage of trauma, the expressions of Col I and Col III, especially Col III, were increased in the ANBP group (P < .05). Studies in vitro demonstrated that tubular formation was significantly increased after ANBP treatment on human vascular endothelial cells in a dose-dependent way. Taken together, our studies revealed that ANBP treatment could accelerate wound healing, promote vascularization, and inhibit inflammation, suggesting the potential clinic application of ANBP for diabetes mellitus and refractory wounds.


Assuntos
Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Cicatrização/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
PLoS One ; 9(12): e112274, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25489732

RESUMO

The four-herb Chinese medicine ANBP is a pulverized mixture of four herbs including Agrimonia Eupatoria (A), Nelumbo Nucifera Gaertn (N), Boswellia Carteri (B) and Pollen Typhae Angustifoliae (P). The combination of the four herbs was first described in Chinese canonical medicine about 2000 years ago for treatment of various trauma disorders, such as hemostasis, antiinflammatory, analgesia, and wound healing, etc. However, the precise mechanisms of ANBP are still unclear. In our study, using rabbit ear hypertrophic scar models of full-thickness skin defect, we showed that local ANBP treatment not only significantly enhanced wound healing by relieving inflammation, increasing formation of granulation tissue and accelerating re-epithelialization, but also reduced scar formation by decreasing collagen production, protuberant height and volume of scars, and increasing collagen maturity. We demonstrated that these effects of ANBP are associated with transforming growth factor (TGF)-ß1-mediated signalling pathways through Smad-dependent pathways. ANBP treatment significantly increased expression of TGF-ß1 and Smad2/3 mRNA at the early stage of wound healing, and led to markedly decrease expression of TGF-ß1 and Smad2/3 compared with the control group after 14 days post-wounding. Taken together, our results defined a bidirectional regulation role of ANBP for TGF-ß1/Smad pathway in promoting wound healing and alleviating scar formation, which may be an effective therapy for human wounds at the earliest stage.


Assuntos
Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/fisiopatologia , Colágeno/metabolismo , Orelha/patologia , Orelha/fisiopatologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Pós , Coelhos , Proteínas Smad/metabolismo , Temperatura Ambiente
14.
Yao Xue Xue Bao ; 49(5): 656-60, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25151737

RESUMO

One new dicyclopeptide cyclo-(L-N-methyl Glu-L-N-methyl Glu) (1), together with one new natural dicyclopeptide cyclo-(L-methyl Glu ester-L-methyl Glu ester) (2), and two known dicyclopeptides cyclo-(L-methyl Glu ester-L-Glu) (3), and cyclo-(L-Glu-L-Glu) (4), were isolated from the aerial parts of Dianthus chinensis L. Their structures were determined by spectroscopic analyses and chemical methods.


Assuntos
Dianthus/química , Plantas Medicinais/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química
15.
Chin J Nat Med ; 12(8): 619-22, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25156288

RESUMO

AIM: To investigate the chemical and bioactive constituents from the stems and leaves of Micromelum integerrimum. METHOD: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and HPLC. Their structures were mainly elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. Their cytotoxicity and antimicrobial activities were tested by the SRB and turbidimetric methods, respectively. RESULTS: Two new phenylpropanoids and two known coumarins were obtained, and their structures were identified as microintegerrin A (1), microintegerrin B (2), scopoletin (3), and scopolin (4). All of the compounds were tested for their cytotoxicity against three cancer cell lines (HeLa, A549, and BGC-823) and for antimicrobial activity against the fungus Candida albicans and the bacterium Staphylococcus aureus. CONCLUSION: Two new phenylpropanoids 1 and 2 were isolated and identified from the stems and leaves of M. intgerrimum. None of the compounds showed cytotoxic or antimicrobial activity at the tested concentration of 20 µg·mL(-1).


Assuntos
Fenilpropionatos/isolamento & purificação , Extratos Vegetais/química , Rutaceae/química , Candida albicans/efeitos dos fármacos , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Fenilpropionatos/química , Fenilpropionatos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta , Escopoletina/isolamento & purificação , Escopoletina/farmacologia , Staphylococcus aureus/efeitos dos fármacos
16.
Fitoterapia ; 93: 98-104, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24393620

RESUMO

Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 µM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 µM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 µM.


Assuntos
Antivirais/isolamento & purificação , Aster/química , Vírus da Hepatite B/efeitos dos fármacos , Triterpenos/isolamento & purificação , Antivirais/química , Antivirais/farmacologia , Replicação do DNA/efeitos dos fármacos , Células Hep G2 , Humanos , Estrutura Molecular , Plantas Medicinais/química , Triterpenos/química , Triterpenos/farmacologia
17.
Tissue Eng Part B Rev ; 20(4): 304-13, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24063625

RESUMO

Cardiovascular disease is a leading cause of death in industrialized countries. Scientists are trying to generate cardiomyocytes in vitro and in vivo to repair damaged heart tissue. Pluripotent reprogramming brings an alternative source of embryonic-like stem cells, and the possibility of regenerating mammalian tissues by first reverting somatic cells to induced pluripotent stem cells, followed by redifferentiating these cells into cardiomyocytes. More recently, lineage reprogramming of fibroblasts directly into functional cardiomyocytes has been reported. The procedure does not involve reverting cells back to a pluripotent stage, and, thus, would presumably reduce tumorigenic potential. Interestingly, lineage reprogramming could be used for in situ conversion of cell fate. Moreover, zebrafish-like regenerative mechanism in mammalian heart tissue, which was observed in mice within the first week of postpartum, should be further addressed. Here, we review the landmark progresses of the two major reprogramming strategies, compare their pros and cons in cardiovascular regeneration, and forecast the future directions of cardiac repair.


Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Regeneração , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/transplante , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/transplante , Camundongos , Miocárdio/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/transplante
18.
Molecules ; 18(12): 14585-96, 2013 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-24287992

RESUMO

Five new shionane-type triterpenes, astataricusones A-D (compounds 1-4) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configurations of 1 and 4 was determined by single crystal X-ray diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg secretion with an IC50 value of 23.5 µM, while 2 and 6 showed inhibitory activities on HBeAg secretion with IC50 values of 18.6 and 40.5 µM, and cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 µM, respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA replication with IC50 values of 2.7 and 30.7 µM, respectively.


Assuntos
Antivirais/química , Aster/química , Triterpenos/química , Cristalografia por Raios X , Vírus da Hepatite B/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Triterpenos/farmacologia
19.
PLoS One ; 8(10): e75334, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24116036

RESUMO

Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature.


Assuntos
Momordica charantia , Proteínas de Plantas/isolamento & purificação , Inibidores da Tripsina/isolamento & purificação , Sequência de Aminoácidos , Espectroscopia de Ressonância Magnética , Proteínas de Plantas/metabolismo , Conformação Proteica , Dobramento de Proteína , Espectrometria de Massas em Tandem , Inibidores da Tripsina/metabolismo
20.
J Ethnopharmacol ; 149(2): 431-7, 2013 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-23850835

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Monochasma savatieri Franch. ex Maxim is used for treating many diseases in Traditional Chinese Medicine. AIM OF THE STUDY: The present study was designed to evaluate antibacterial, anti-inflammatory activities and toxicity of the total phenylethanoid glycosides from Monochasma savatieri Franch. ex Maxim (TPG). MATERIALS AND METHODS: The antibacterial activity of TPG was checked by MIC and MBC in vitro; survival of mice with Pseudomonas aeruginosa or Staphylococcus aureus infection-induced sepsis was investigated to evaluate antibacterial activity of TPG in vivo. Additionally, antibacterial activities of TPG were also investigated in a Pseudomonas aeruginosa infection-induced pneumonia in the mice model. Cotton pellet induced granuloma and xylene induced ear swelling in mice models were used to quantify the anti-inflammatory activity. RESULTS: TPG showed a significant possess bacteriostatic properties against five bacteria strains at a concentration between 0.0625 and 16 mg/ml. Moreover, TPG has bactericidal activity against Pseudomonas aeruginosa, Streptococcus pneumoniae or Escherichia coli. TPG (60, 120, and 180 mg/kg) prolonged survival rate of mice with Pseudomonas aeruginosa or Staphylococcus aureus infection-induced sepsis. In addition, TPG (180 mg/kg) could reduce the bacterial colony-forming units in lung tissue. Furthermore, TPG (60-180 mg/kg) had significantly reduced xylene-induced ear edema and granulomat formation induced by cotton pellet at a dose-dependent manner. In addition, administration of TPG (1.5 g/kg) for 15 days did not result in toxicities in liver, kidney, spleen and thymus tissue in rats. CONCLUSION: These results indicated that TPG might be useful for the development of a novel treatment for respiratory infections or pneumonia caused by Pseudomonas aeruginosa or Staphylococcus aureus.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Glicosídeos/uso terapêutico , Orobanchaceae , Infecções por Pseudomonas/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Glicosídeos/farmacologia , Granuloma/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Fitoterapia , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico
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