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1.
Front Pharmacol ; 14: 1123945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663258

RESUMO

Objective: The effect of oxygen therapy on the prognosis of chronic obstructive pulmonary disease (COPD) with nocturnal hypoxemia (NOD) has been controversial. Therefore, this study systematically evaluated the relevant literature and included it into randomized controlled studies for meta-analysis to evaluate the efficacy and prognosis. Methods: We searched PubMed, EMBASE, web of science, Cochrane, China HowNet and Wanfang database for the literature on the prognosis of COPD patients with simple NOD from the establishment of the database to 30 June 2022. The outcome indicators were death and aggravation of the disease. The efficacy evaluation measures were pulmonary function and arterial blood gas results. The publication bias and heterogeneity of the included studies were evaluated. Results: A total of 621 patients from 5 studies were included in this meta-analysis, and there was no publication bias in the included studies. The total mortality of long-term oxygen therapy (LTOT) in COPD patients with simple NOD in oxygen therapy group (RR = 1.04; 95% CI: 0.81-1.33, p = 0.77), mortality (RR = 0.87; 95% CI: 0.58-1.31, p = 0.50), risk of progression to LTOT events (RR = 1.07; 95% CI: 0.76-1.51, p = 0.71). PaO2 in patients with COPD and simple NOD in oxygen therapy group was higher than that in non-oxygen therapy group (mean difference (MD) = 13.47; 95% CI: 3.49-23.46, p = 0.008), the decrease of PaCO2 level was not statistically significant (MD = -10.05; 95% CI: -26.36-6.27, p = 0.23). Conclusion: Oxygen therapy can improve the prognosis of blood oxygen partial pressure in COPD patients with simple NOD, but oxygen therapy has no significant effect on the survival rate, controlling the progression of the disease to LTOT and reducing the partial pressure of carbon dioxide.

2.
iScience ; 24(11): 103177, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34712915

RESUMO

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.

3.
Cell Death Discov ; 7(1): 11, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446662

RESUMO

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit ß-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both ß-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2-ß-arrestin1/2-STAT3 signalosome is critical for glutamate-induced cell proliferation.

4.
Life Sci ; 240: 117091, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760102

RESUMO

Mounting evidences indicated that elevated iron levels in the substantia nigra (SN) have been concerned as the underlying mechanisms of neurodegenerative diseases, including Parkinson's disease (PD). The present study used the 1-Methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP)-treated cynomolgus monkeys for PD to evaluate the usability of SWI for assessing iron deposition in the cerebral nuclei of PD. The results showed that susceptibility-weighted imaging (SWI) phase values of the ipsilateral (MPTP-lesion side) SN of MPTP-treated monkeys were lower than those in the contralateral SN of MPTP-treated monkeys and the same side of Control monkeys, suggesting that iron deposition were elevated in the affected side SN of MPTP-treated monkeys. Whereas MPTP has not effects on the SWI phase values in other detected brain regions of monkeys, including red nucleus (RN), putamen (PUT) and caudate nucleus (CA). Furthermore, ICP-MS results showed that MPTP increased the iron levels in MPTP injection side, but no in the ipsilateral striatum. Additionally, MPTP treatment did not affect the calcium and manganese levels in the detected brain regions of monkeys. However, Pearson correlation analysis results indicated that there were not relationship between SWI phase values in MPTP-lesion side of SN with the behavioral score, tyrosine hydroxylase (TH)-positive cells number and iron levels in the MPTP-lesion side of midbrain. Taken together, the results confirm the involvement of SN iron accumulations in the MPTP-treated monkey models for PD, and indirectly verify the usability of SWI for the measurement of iron deposition in the cerebral nuclei of PD.


Assuntos
Ferro/metabolismo , Intoxicação por MPTP/metabolismo , Transtornos Parkinsonianos/metabolismo , Animais , Comportamento Animal , Encéfalo/diagnóstico por imagem , Cálcio/metabolismo , Intoxicação por MPTP/diagnóstico por imagem , Macaca fascicularis , Imageamento por Ressonância Magnética , Masculino , Manganês/metabolismo , Espectrometria de Massas , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/diagnóstico por imagem , Substância Negra/metabolismo , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismo
5.
Neurosci Lett ; 675: 127-132, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29199095

RESUMO

OBJECTIVE: To analyze the microstructure of brain white matter according to diffusion tensor imaging (DTI) based on tract-based spatial statistics (TBSS) in early Parkinson's disease (PD). MATERIALS AND METHODS: A total of 31 age- and sex-matched early PD patients and 22 healthy volunteers were recruited in the present study. DTI was performed, and the data analyzed with fsl4.0 software. The fractional anisotropy (FA) was compared between both groups with an independent t test, and the differential area was analyzed. White matter fiber tracts with significant difference in FA between the two groups were selected, and their FAs were measured. Pearson's correlation analysis was employed to analyze the unified Parkinson's disease rating scale (UPDRS) score and its association with FA of different tracts. RESULTS: When compared with healthy volunteers, early PD patients had reduced FA in the following areas: bilateral anterior corona radiate, upper corona radiate, fasciculus arcuatus, crus anterius capsulae internae, crus posterius capsulae internae, capsula externa, posterior thalamic radiation, optic radiation, sagittal layer (including fasciculus arcuatus and inferior fronto-occipital fasciculus), crura fornicis, stria terminalis, fornix, genu, body and pad of corpus callosum, left unciform fasciculus, right cingulate bundle, right medipeduncle, and arcuate fibers in the bilateral frontal, temporal, and occipital lobes (P < 0.05). When compared with healthy volunteers, early PD patients showed abnormal FA of fasciculus in the white matter mainly in following areas: bilateral crus anterius capsulae internae, bilateral capsula externa, right anterior corona radiate, body and pad of bilateral corpus callosum, and left sagittal layer (including fasciculi longitudinalis inferior and fasciculus occipitofrontalis inferior) (P < 0.05). In addition, in early PD patients, the UPDRS score and movement score had no relationship with the FA of different fasciculi in the white matter (P > 0.05). CONCLUSION: There is wide alteration of white matter microstructure in early PD patients, which is characterized by disruption of projection fibers in the descending pathway, limbic system-related fasciculi, corpus callosum, thalamus after radiation, posterior thalamic radiation, Gratiolet's bundle and other fasciculi in the white matter.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Idoso , Anisotropia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia
6.
Bioorg Med Chem Lett ; 27(6): 1441-1445, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28214077

RESUMO

As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Flavonoides/farmacologia , Linhagem Celular Tumoral , Humanos
7.
J Registry Manag ; 43(4): 187-94, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29595921

RESUMO

BACKGROUND: Primary benign and borderline (BB) brain tumors have been reportable since 2004 by population-based cancer registries in the United States. Because these tumors often are diagnosed clinically at nonhospital settings, underreporting is a big concern. Despite this, the magnitude and geographic variations in underreporting are unknown. The objectives of this study are to assess variations in BB brain tumor incidence rate by registry and trend in comparison to malignant brain tumors, as well as to identify the factors associated with the completeness of BB brain tumor reporting. METHODS: North American Association of Central Cancer Registries (NAACCR) Cancer in North America (CINA) Deluxe 1995­2012 Analytic File, which included data from 47 US population-based cancer registries, was used. Age-adjusted incidence rate and average annual percent change (APC) were calculated. Correlation coefficients were used to assess the relationships between incidence rates and clinical factors. RESULTS: The overall age-adjusted incidence rate was 14.2 per 100,000 for BB brain tumors and 6.6 per 100,000 for malignant brain tumors. The age-adjusted incidence rates of BB brain tumors varied by registry from 9.8 per 100,000 to 19.9 per 100,000, whereas the variations in malignant brain tumors were much smaller from 4.1 per 100,000 to 7.7 per 100,000. BB brain tumor cases were more likely than malignant brain tumors to be diagnosed through radiography without microscopic confirmation or surgery. Overall, the BB brain tumor incidence rate significantly increased by 2.3% per year from 2004 to 2012. In contrast, incidence rates of malignant brain tumors significantly decreased by 0.9% per year in the same period. Higher BB brain tumor incidence rates were significantly associated with higher proportions of cases without microscopic confirmation or surgery. These associations were not observed for malignant brain tumors. CONCLUSIONS: Incidence rates of BB brain tumors varied substantially across 47 US registries and were higher than those of malignant brain tumors in the United States. The variations in incidence rate of BB brain tumors may be largely attributable to difference in identifying clinically diagnosed cases. The increasing incidence rate of BB brain tumors may reflect improved case ascertainment rather than a biological trend. Key words:


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Sistema de Registros , Feminino , Humanos , Incidência , Masculino , Vigilância da População , Estados Unidos/epidemiologia
8.
Int J Clin Exp Med ; 8(3): 3974-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064299

RESUMO

AIM: To investigate the value of conventional MRI techniques combined with MR sialography on T2-3D-DRIVE in the diagnosis of Sjögren syndrome (SS). METHODS: 107 patients were divided into SS group and non-SS group. Conventional MRI techniques, such as T1WI, T2WI, and STIR images were used for changes of fat signal in the parotid gland, while the MR sialography were used for ducts dilation of the parotid gland. RESULTS: Among 93 SS patients, MRI identified abnormal fat deposit in the parotid glands in 86 patients. The fat signal based on MRI images showed 7 patients were in stage 0, 28 in stage 1, 14 in stage 2, 32 in stage 3 and 12 in stage 4. T2-3D-DRIVEMR MR sialography identified peripheral ducts dilation in 86 patients. The duct dilation based on MR sialography showed 7 patients in stage 0, 14 patients in stage 1, 44 patients in stage 2, 26 patients in stage 3, and 2 patients in stage 4. On MRI and MR sialography, both had a positive diagnostic rate of 92.5%. When MRI and MR sialography techniques were used together, the positive diagnostic rate increased to 96.8%. However, Kappa test showed that the MRI fat signal staging and MR sialogrpahy duct dilation staging had statistical difference (Kappa = 0.241, P = 0.000). CONCLUSION: T2-3D-DRIVE MR sialography detects peripheral ducts dilation in parotid glands with unmatched spatial resolution, also MRI fat suppression techniques detect diffusive fat deposit in parotid glands with high accuracy. Combining two techniques will provide optimal diagnosis workup for SS.

9.
PLoS One ; 9(4): e93900, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24718592

RESUMO

OBJECTIVE: The current study was designed to evaluate the sensitivity, feasibility, and effectiveness of the pallidal index (PI) serving as a biomarker of brain manganese (Mn) accumulation, which would be used as an early diagnosis criteria for Mn neurotoxicity. METHODS: The weighted mean difference (WMD) of the PI between control and Mn-exposed groups was estimated by using a random-effects or fixed-effects meta-analysis with 95% confidence interval (CI) performed by STATA software version 12.1. Moreover, the R package "metacor" was used to estimate correlation coefficients between PI and blood Mn (MnB). RESULTS: A total of eight studies with 281 occupationally Mn-exposed workers met the inclusion criteria. Results were pooled and performed with the Meta-analysis. Our data indicated that the PI of the exposed group was significantly higher than that of the control (WMD: 7.76; 95% CI: 4.86, 10.65; I2 = 85.7%, p<0.0001). A random effects model was used to perform meta-analysis. These findings were remarkably robust in the sensitivity analysis, and publication bias was shown in the included studies. Seven out of the eight studies reported the Pearson correlation (r) values. Significantly positive correlation between PI and MnB was observed (r = 0.42; 95% CI, 0.31, 0.52). CONCLUSIONS: PI can be considered as a sensitive, feasible, effective and semi-quantitative index in evaluating brain Mn accumulation. MnB can also augment the evaluation of brain Mn accumulation levels in the near future. However, the results should be interpreted with caution.


Assuntos
Química Encefálica , Globo Pálido/química , Imageamento por Ressonância Magnética/métodos , Manganês/farmacocinética , Metalurgia , Exposição Ocupacional , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/patologia , Ensaios Clínicos como Assunto , Humanos , Manganês/sangue , Manganês/toxicidade , Compostos de Manganês/farmacocinética , Concentração Máxima Permitida , Óxidos/farmacocinética , Óxidos/toxicidade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Neurotoxicology ; 45: 285-92, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24680838

RESUMO

Increased manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn exposure occurs in different occupational settings, where the airborne Mn level and the size of respirable particulates may vary considerably. Recently the importance of the role of the cerebral cortex in Mn toxicity has been highlighted, especially in Mn-induced neuropsychological effects. In this study we used magnetic resonance imaging (MRI) to evaluate brain Mn accumulation using T1 signal intensity indices and to examine changes in brain iron content using T2* contrast, as well as magnetic resonance spectroscopy (MRS) to measure exposure-induced metabolite changes non-invasively in cortical and deep brain regions in Mn-exposed welders, Mn-exposed smelter workers and control factory workers with no measurable exposure to Mn. MRS data as well as T1 signal intensity indices and T2* values were acquired from the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. Smelters were exposed to higher air Mn levels and had a longer duration of exposure, which was reflected in higher Mn levels in erythrocytes and urine than in welders. Nonetheless, welders had more significant metabolic differences compared to controls than did the smelter workers, especially in the frontal cortex. T1 hyperintensities in the globus pallidus were observed in both Mn-exposed groups, but only welders showed significantly higher thalamic and hippocampal T1 hyperintensities, as well as significantly reduced T2* values in the frontal cortex. Our results indicate that (1) the cerebral cortex, in particular the frontal cortex, is clearly involved in Mn neurotoxic effects and (2) in spite of the lower air Mn levels and shorter duration of exposure, welders exhibit more extensive neuroimaging changes compared to controls than smelters, including measurable deposition of Mn in more brain areas. These results indicate that the type of exposure (particulate sizes, dust versus fume) and route of exposure play an important role in the extent of Mn-induced toxic effects on the brain.


Assuntos
Poluentes Ocupacionais do Ar/metabolismo , Química Encefálica , Intoxicação por Manganês/metabolismo , Exposição Ocupacional , Adulto , Poluentes Ocupacionais do Ar/análise , Eritrócitos/química , Humanos , Imageamento por Ressonância Magnética , Masculino , Manganês/metabolismo , Manganês/urina , Pessoa de Meia-Idade , Tamanho da Partícula , Soldagem
11.
PLoS One ; 9(2): e88220, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24505436

RESUMO

Overexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R(2) = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2) = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.


Assuntos
Ferro/efeitos adversos , Manganês/efeitos adversos , Atividade Motora/fisiologia , Exposição Ocupacional/efeitos adversos , Tálamo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adulto , Humanos , Masculino , Exame Neurológico/métodos
12.
Molecules ; 19(2): 1603-7, 2014 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-24473216

RESUMO

A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS.


Assuntos
Éteres/química , Estrutura Molecular , Extratos Vegetais/química , Umbeliferonas/química , Éteres/farmacologia , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Thymelaeaceae/química
13.
Heart Lung Circ ; 23(2): 105-13, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23962886

RESUMO

BACKGROUND: The effect of statin treatment on the long-term prognosis in patients with chronic heart failure (CHF) remains uncertain. This study aimed to answer the question by a meta-analysis. METHODS: The Cochrane databases, MEDLINE and EMBASE, were systematically searched. The eligibility of prospective studies that assigned CHF patients to receive statin treatment and a control (no statin treatment), had defined prognostic outcomes as primary endpoint, and had a minimal follow-up of 12 months was determined. RESULTS: Fifteen studies involving 45,110 patients were included in the analysis. Additional statin treatment was associated with reduced all-cause mortality (risk ratios [RR] = 0.71, 95% confidence intervals [CI] 0.61-0.83) and reduced rehospitalisation rate for heart failure (RR = 0.84, 95% CI 0.74-0.96). Statin treatment, however, had little impact on pump failure mortality, cardiovascular mortality, and sudden cardiac death. Atorvastatin treatment appeared to facilitate to reduce all-cause mortality (lnRR = 0.61, p = 0.05) and rehospitalisation for heart failure (lnRR = 0.44, p = 0.04) compared with non-atorvastatin therapy. CONCLUSIONS: Based on the available data, statins persistently decreased all-cause mortality and the incidence of rehospitalisation for heart failure in CHF patients, and the benefits might be partially associated with use of specific statin.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Atorvastatina , Doença Crônica , Feminino , Seguimentos , Humanos , MEDLINE , Masculino , Estudos Prospectivos
14.
Oncol Rep ; 29(6): 2275-82, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23588374

RESUMO

The present study showed that the combination of dasatinib and combretastatin A-4 (CA-4) exhibited synergistic cytotoxicity in multiple types of cancer, including ovarian, hepatocellular, lung and prostate carcinoma. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis. A clear increase in γ-H2AX expression was observed in the dasatinib+CA-4 group compared with the mono-treatment groups, indicating that dasatinib plus CA-4 may induce double-strand breaks (DSBs) in HO-8910 cells. Moreover, the increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice. Our study is the first to show that the combination of dasatinib with CA-4 could be a novel and promising therapeutic approach for the treatment of cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Dasatinibe , Sinergismo Farmacológico , Humanos , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirimidinas/administração & dosagem , Estilbenos/administração & dosagem , Tiazóis/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Zhongguo Zhen Jiu ; 33(10): 893-6, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24377218

RESUMO

OBJECTIVE: To compare the difference in the efficacy on post-stroke constipation between acupuncture therapy of regulating qi circulation of fe-organ and Shengxue Tongbian Capsules. METHODS: Seventy-five patients of post-stroke constipation were randomized into an acupuncture group (39 cases) and a Chinese medicine group (36 cases). The unit mode comprehensive therapy of stroke was adopted as basic treatment in the two groups. In the acupuncture group, acupuncture therapy of regulating qi circulation of fu-organ was added at Tianshu (ST 25), Zhigou (TE 6), Qihai (CV 6) and Zusanli (ST 36), once every day. In the Chinese medicine group, Shengrue Tongbian Capsules were supplemented for oral administration, once every day, 10 g each time. The clinical symptom score of constipation was observed before treatment, after 1 and 2 weeks treatment in the two groups, respectively. The efficacy in 1 week and 2 weeks of treatment and the adverse reaction were observed. RESULTS: In 1 and 2 weeks of treatment, the clinical symptom score of constipation was reduced significantly as compared with that before treatment in the two groups (all P < 0.05). The improvements in the acupuncture group were significant than those in the Chinese medicine group in 2 weeks of treatment (8.03 +/- 2.38 vs 9.20 +/- 2.45, P < 0.05). Concerning to the occurrence of adverse reaction, there was 1 case of local bruises in needling local site in the acupuncture group; and there were 1 case of abdominal pain, 3 cases of diarrhea and 2 cases of nausea and vomiting in the Chinese medicine group. CONCLUSION: Both the acupuncture therapy of regulating qi circulation of fu-organ and Shengxue Tongbian Capsules achieve the significant efficacy on post-stroke constipation. The efficacy of the acupuncture therapy of regulating qi circulation of fe-organ is better and the adverse reaction is less after long-term persistent treatment.


Assuntos
Terapia por Acupuntura , Constipação Intestinal/terapia , Qi , Acidente Vascular Cerebral/complicações , Idoso , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Defecação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 41(4): 430-3, 449, 2012 07.
Artigo em Chinês | MEDLINE | ID: mdl-22927079

RESUMO

OBJECTIVE: To develop a method for simultaneous assay of propulsion and absorption in small intestine. METHODS: The mice were administrated through gastric tube with mixed reagents containing 0.12% phenol red, D-xylose (1.25%, 2.5% and 5%) and 15% gelatin. The influence of phenol red on D-xylose absorption and the influence of D-xylose on small intestine propulsion rate were investigated by measuring serum concentration of D-xylose with phloroglucinol method. RESULTS: At 10 min, no significant difference was found between 5% D-xylose mixed reagent group and 5% D-xylose control. At 15 min, small intestine propulsion rate in 5% D-xylose mixed reagent group, but not in 2.5% and 1.25% D-xylose mixed reagent groups, was significantly higher than in phenol red control (P<0.05). CONCLUSION: Gastric administration of mixed reagent containing 0.12% phenol red, 5% D-xylose and 15% gelatin can simultaneously assay propulsion and absorption of small intestine in mice.


Assuntos
Bioensaio/métodos , Absorção Intestinal , Intestino Delgado/fisiologia , Peristaltismo , Animais , Intestino Delgado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fenolsulfonaftaleína/farmacocinética , Xilose/farmacocinética
17.
Molecules ; 17(7): 7792-7, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22735781

RESUMO

A new 3,3''-biflavanone, sikokianin D (1), was isolated from the roots of Wikstroemia indica, together with two known compounds. Their structures were elucidated by chemical evidence and spectral analyses, including HR-ESI-MS, and 1D- and 2D-NMR techniques.


Assuntos
Biflavonoides/isolamento & purificação , Raízes de Plantas/química , Wikstroemia/química , Biflavonoides/química , Espectroscopia de Ressonância Magnética
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 41(2): 171-7, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22499514

RESUMO

OBJECTIVE: To establish a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for detection of nine penicillin residues in milk. METHODS: The samples were precipitated with acetonitrile and degreased with n-hexane for pre-processing. The chromatography was performed by reversed-phase HPLC in a C18 column and eluted gradiently on line for 11 min. The mobile phases were water with formic acid (pH 3.1) and acetonitrile-water with formic acid (pH 3.1). By optimizing the mass condition, the method was operated by multiple-reaction monitoring (MRM) and quantitated by external standard calibration. RESULTS: The standard curves were linear in concentration range of 0.4 approximately 400 µg/L and all nine penicillins showed a good linear relationship in the milk matrix (r>0.990). The detection limit of the method was from 0.1 to 0.8 µg/L while the limit of quantification was from 0.3 to 2.6 µg/L. The average recoveries were higher than 80%. The within-day precisions were less than 8.5%. CONCLUSION: The established method is convenient, rapid and accurate and meets the requirement of monitoring penicillin residues in milk.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Resíduos de Drogas/análise , Leite/química , Penicilinas/análise , Espectrometria de Massas em Tandem/métodos , Animais
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(4): 374-9, 2011 07.
Artigo em Chinês | MEDLINE | ID: mdl-21845749

RESUMO

OBJECTIVE: To investigate the effects of purple sweet potato flavonoids (PSPF) on blood glucose and lipids levels in diabetic rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg.kg(-1)) in rats. The changes of fasting blood glucose and lipids levels in serum and body weight, food and fluid intake of diabetic rats treated with PSPF were examined. RESULTS: Diabetic symptoms were ameliorated after rats were fed with PSPF. The fasting blood glucose (FBG), GSP, TC, TG, LDL-C were decreased and serum HDL-C levels were increased (P<0.01) in high, medium dose PSPF groups; while FBG, serum GSP, TG, LDL-C were also improved in low dose group (P<0.05 or P<0.01). CONCLUSION: Purple sweet potato flavonoids can decrease the blood glucose and lipids levels in diabetic rats.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Flavonoides/farmacologia , Ipomoea batatas/química , Lipídeos/sangue , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(4): 380-3, 2011 07.
Artigo em Chinês | MEDLINE | ID: mdl-21845750

RESUMO

OBJECTIVE: To extract and isolate the component from myrsinane-type diterpenes of Euphorbia prolifera. METHODS: Petroleum extraction and chromatography on the silica gel were used to extract and isolate the diterpenes of Euphorbia prolifera. RESULTS: Eight components of myrsinol diterpenes were isolated, namely: Proliferin A(1), Proliferin B (2), Proliferin C(3), Proliferin D(4), Euphorprolitherin B(5), Euphorprolitherin D(6), SPr5(7) and 14-desoxo-3-O-prorionyl-5, 15-di-O-acetyl-7-O-nicotinoyl-myrsinol-14ß-acetate(8). Their structures were identified with mass-spectroscopic methods and NMR techniques. The cytotoxicity of compounds 1, 2, and 4 against cancer cells was evaluated, with compound 1 being active against A2780 cancer cells (IC(50) 7.7 µmol/L). CONCLUSION: Myrsinane-type diterpene Proliferin A from Euphorbia prolifera shows cytotoxic effect against human ovarian cancer cell line A2780.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Humanos
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