Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Sci Rep ; 9(1): 14200, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578346

RESUMO

We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

3.
Neuropharmacology ; 141: 89-97, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30145320

RESUMO

Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are associated with deficits in various cognitive domains. To distinguish between developmental and adult functions of ADK, we used two transgenic mouse lines with widespread disruption of ADK expression in the adult brain, but differences in the onset of ADK deletion. Specifically, we compared Nestin-Cre+/-:ADK-floxfl/fl (ADKΔBrain) mice with global loss of ADK in the whole brain, beginning in mid-gestation and persisting for life, with Gfa2-Cre+/-:ADK-floxfl/fl (ADKΔAstro) mice that have normal ADK expression throughout development, but lose astrocyte-specific ADK-expression in young adulthood. Because ADK-expression in adulthood is generally confined to astrocytes, adult ADKΔAstro mice show a similar expression profile of ADK in key areas of the brain related to neuropsychiatric behavior, compared to adult ADKΔBrain mice. We sought to determine a neurodevelopmental role of ADK on the expression of psychiatric behaviors in adult male and female mice. Adult ADKΔBrain mice showed significant deficits in social memory in males, significant contextual learning impairments in both sexes, and a hyper-responsiveness to amphetamine in males. In contrast, ADKΔAstro mice showed normal social memory and contextual learning but hypo-responsiveness to amphetamine in males. Our results demonstrate a key developmental role of ADK in mediating behaviors in adulthood related to neuropsychiatric disease and support the greater prevalence of these disorders among males.


Assuntos
Adenosina Quinase/fisiologia , Sensibilização do Sistema Nervoso Central/genética , Aprendizagem/fisiologia , Memória/fisiologia , Caracteres Sexuais , Adenosina Quinase/genética , Fatores Etários , Anfetamina/farmacologia , Animais , Feminino , Proteínas de Choque Térmico HSP40/genética , Masculino , Camundongos , Camundongos Transgênicos , Nestina/genética
4.
Pestic Biochem Physiol ; 147: 153-161, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29933986

RESUMO

The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.


Assuntos
Antifúngicos/farmacologia , Bacillus/química , Colletotrichum/efeitos dos fármacos , Peixe-Zebra , Animais , Antifúngicos/toxicidade , Colletotrichum/fisiologia , Produtos Agrícolas/microbiologia , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Mangifera/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Esporos Fúngicos/efeitos dos fármacos , Testes de Toxicidade Aguda
5.
Spinal Cord ; 56(1): 90, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28719579

RESUMO

This corrects the article DOI: 10.1038/sc.2016.36.

6.
Eur Rev Med Pharmacol Sci ; 21(18): 3985-3989, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29028106

RESUMO

OBJECTIVE: The objective of this study was to examine the correlation between the presence of primary iris-ciliary cysts and the intraocular pressure. PATIENTS AND METHODS: Sixty patients with short-sightedness undergoing routine examination for laser vision correction in our hospital in 2003 were enrolled. Patients with known high intraocular pressure and risk of glaucoma were excluded from the study. A total of 119 eyes were examined by the Ultrasound Biomicroscope (UBM), and the presence of the primary iris-ciliary cysts was confirmed. Intraocular pressure was measured by using a blowing tonometer for each eye in triplicate. Through Pentacam correction of intraocular pressure using the Ehlers formula, the influence of the thickness of central cornea on intraocular pressure was excluded. RESULTS: Among all participants, 62 eyes (52.1%) were with high myopia, 57 eyes (47.9%) with low and moderate myopia, 27 eyes (22.7%) with single cyst, 20 eyes (16.8%) with multiple cysts, and 72 eyes (60.5%) were free from cysts. Moreover, the intraocular pressure was found within the normal range in 72 eyes (60.5%), and abnormally high in 47 eyes (39.5%). CONCLUSIONS: Our results showed that the presence of primary iris-ciliary cysts and the intraocular pressure were positively correlated, with a correlation coefficient of 0.235 (p = 0.01). These findings may prove useful for prediction and screening of high intraocular pressure.


Assuntos
Corpo Ciliar/patologia , Cistos/patologia , Pressão Intraocular/fisiologia , Iris/patologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Microscopia Acústica , Miopia/complicações , Miopia/diagnóstico , Adulto Jovem
7.
Eur Rev Med Pharmacol Sci ; 21(17): 3794-3800, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28975989

RESUMO

OBJECTIVE: MiRNAs are small, noncoding RNA molecules that serve as important regulators of cancer-related processes. Abnormal expression of miR-577 has been found in several tumors. However, the expression pattern and biological function of miR-577 in progression of papillary thyroid cancer (PTC) remain unknown. This study is aimed to determine its expression pattern and explore the function underlying the mechanism of miR-577 in PTC. PATIENTS AND METHODS: Using quantitative RT-PCR, we detected miR-577 expression in PTC cell lines and primary tumor tissues. MTT assay and colony formation were performed to measure the viabilities of tumor cells. Transwell invasion and migration assays were used to test the invasion and migration of PTC cells transfected with miR-577 mimic. TargetScan, miRanda and PicTar were used to analyze whether sphingosine kinase 2 (SphK2) was a potential target gene. Next, the direct target gene of miR-577 was also identified by luciferase reporter assays and Western blot analysis. RESULTS: The results showed that miR-577 was significantly downregulated in PTC tissues and cell lines. The up-regulation of miR-577 inhibited the proliferation, migration and invasion of PTC cells in vitro. Furthermore, bioinformatics analysis indicated that SphK2 was a putative target of miR-577. A luciferase reporter assay further confirmed that SphK2 was a direct target of miR-577. The results of Western blot indicated that the expression level of miR-577 was negatively correlated with the expression level of SphK2 in PTC tissues. In addition, knockdown of SphK2 significantly suppressed PTC cells proliferation, migration and invasion. CONCLUSIONS: Our findings indicate that miR-577 is a potential tumor suppressor in PTC by targeting SphK2, and may be a potential therapeutic target in PTC.


Assuntos
Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Movimento Celular , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Fosfotransferases (Aceptor do Grupo Álcool)/biossíntese , Câncer Papilífero da Tireoide , Regulação para Cima
8.
Eur Rev Med Pharmacol Sci ; 21(16): 3538-3542, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28925492

RESUMO

OBJECTIVE: Screening genes in patients suffering clinically sporadic deafness, using DNA microarray, and evaluating the application value of the clinical detection. PATIENTS AND METHODS: DNA extracted from patients' venous blood was amplified by PCR, and hybridization was carried out in a myriad class clean room. Nine mutation sites of four deaf genes commonly seen in Chinese people were tested. RESULTS: Among 24 patients, 7 cases with mutations were detected, with a positive rate of 29.17%. These include 4 cases with GJB2 gene mutation (16.67%), of which 1 case with 176 del 16 site heterozygous mutation; 1 with 235 del C site homozygous mutation; 2 with 299 del AT site heterozygous mutation; 1 with SLC26A4 gene IVS7-2A>G site heterozygous mutation (4.17%), 2 with mitochondrion 12SrRNA gene1555A>G site homogeneous mutation (8.33%). No GJB3 gene mutation was detected. CONCLUSIONS: Gene chip technology of hereditary hearing loss can detect related mutation sites of hearing loss rapidly and with high-throughput, which meets the demands of clinical deaf gene detection.


Assuntos
Conexinas/genética , Testes Genéticos/métodos , Perda Auditiva/diagnóstico , Análise de Sequência com Séries de Oligonucleotídeos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Surdez/diagnóstico , Feminino , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Proteínas de Membrana Transportadoras , Mitocôndrias , Mutação , Reação em Cadeia da Polimerase , Transportadores de Sulfato , Adulto Jovem
9.
Spinal Cord ; 54(11): 933-941, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27001129

RESUMO

STUDY DESIGN: Transplanted primates' neural stem cells (NSCs) tissue engineering complex into spinal cord injury (SCI) model rats, analyze and evaluate the long-term effects of repairing. OBJECTIVES: Primate NSCs were cultured in self-assembling peptide nanofiber scaffolds to repair SCI. SETTING: Sun Yat-sen Memorial Hospital, Guangzhou, China. METHODS: Primate NSCs were isolated and cultured in self-assembling peptide nanofiber scaffolds. T10 SCI model was established; the rats were randomly divided into four groups: NSC plus self-assembling peptide scaffold group; NSC group; self-assembling peptide scaffold group; and control group. Immunohistochemical staining and electronic microscope were used to investigate the growth and differentiation of transplanted NSCs. The motor function of the hind limbs of rats was evaluated (P<0.05 was considered as statistically significant). RESULTS: NSCs and NSCs cultured in self-assembling peptide nanofiber scaffolds could be induced to differentiation into neurons, glial cells and oligodendrocytes in vitro. The primate NSC culture was established in self-assembling peptide scaffolds. No significant difference was seen in the differentiation rate between primate NSCs cultured in self-assembling peptide nanofiber scaffolds and primate NSCs cultured in regular medium. The motor function of the hind limbs in the NSC plus self-assembling peptide scaffold group was significantly better than that of the other three groups. In addition, the NSCs of the NSC group mainly differentiated into astrocytes. CONCLUSION: Transplantation of primate NSCs cultured in self-assembling peptide scaffolds is efficient for repairing the injured spinal cord and for improving the motor function of spinal cord in rats. SPONSORSHIP: The National Natural Science Foundation of China; Science and Technology Office of Guangdong Province.


Assuntos
Nanofibras , Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Extremidade Inferior/fisiopatologia , Macaca fascicularis , Microscopia Eletrônica , Atividade Motora/fisiologia , Nanofibras/ultraestrutura , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Neurônios/ultraestrutura , Oligodendroglia/fisiologia , Oligodendroglia/ultraestrutura , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/ultraestrutura
10.
Braz. j. med. biol. res ; 49(3): e4733, Mar. 2016. tab
Artigo em Inglês | LILACS | ID: lil-771939

RESUMO

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fístula Arteriovenosa/complicações , Hipertensão Pulmonar/etiologia , Diálise Peritoneal/efeitos adversos , Proteína C-Reativa/análise , China/epidemiologia , Hipertensão Pulmonar/epidemiologia , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Peptídeo Natriurético Encefálico/sangue , Fósforo/sangue , Estudos Prospectivos , Fatores de Risco
11.
Braz J Med Biol Res ; 49(3)2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26840710

RESUMO

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.


Assuntos
Fístula Arteriovenosa/complicações , Hipertensão Pulmonar/etiologia , Diálise Peritoneal/efeitos adversos , Idoso , Proteína C-Reativa/análise , China/epidemiologia , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fósforo/sangue , Estudos Prospectivos , Fatores de Risco
12.
Genet Mol Res ; 14(1): 719-29, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25730009

RESUMO

Several previous studies have demonstrated that elevated levels of fibroblast growth factor-23 (FGF-23) may be involved in atherosclerosis and contribute to the high mortality rate of peritoneal dialysis (PD) patients. The aim of this study was to determine the precise role of FGF-23 in the pathogenesis of atherosclerosis in PD patients. Between April 2009 and January 2012, 62 PD patients and 25 control subjects were included in the study. An enzyme-linked immunosorbent assay was conducted to test for plasma FGF-23 levels. Carotid artery intima-media thickness (CIMT), left ventricular mass index (LVMI), and myocardial performance index (MPI) were determined by ultrasonography. Plasma Ca(2+), P(3+), calcium-phosphorus product, parathyroid hormone, N-terminal pro-brain natriuretic peptide, and cardiac troponin I were also detected. Plasma FGF-23 levels in PD patients were significantly higher than those in control subjects. PD patients with CIMT > 1.0 mm showed the highest levels of FGF-23. Plasma P(3+), calcium-phosphorous product, plasma parathyroid hormone, CIMT, LVMI, and MPI levels were positively associated with plasma FGF-23 levels. Multiple-stepwise regression analyses revealed that plasma P(3+), plasma parathyroid hormone, CIMT, LVMI, and MPI levels were strongly associated with plasma FGF-23 levels. However, no correlations were observed in plasma N-terminal pro-brain natriuretic hormone and cardiac troponin I levels. Plasma FGF- 23 levels may play an important role in the initiation and progression of atherosclerosis. Thus, detecting and defining plasma FGF-23 levels may be a promising biomarker for the early detection of atherosclerosis in PD patients.


Assuntos
Aterosclerose/genética , Biomarcadores/sangue , Fatores de Crescimento de Fibroblastos/sangue , Diálise Peritoneal , Adulto , Idoso , Aterosclerose/sangue , Aterosclerose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Hormônio Paratireóideo/sangue , Fatores de Risco , Troponina I/sangue
13.
Phys Chem Chem Phys ; 16(11): 5066-70, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24487648

RESUMO

This work reports on the use of an internal electrostatic field to facilitate charge separation at inorganic-organic interfaces, analogous to those in hybrid solar cells. Systematic charge transfer studies show that the donor-acceptor charge transfer rate is highly sensitive to the direction of the internal electric field.

14.
Spinal Cord ; 51(3): 196-201, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23045300

RESUMO

OBJECTIVES: To quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in a porcine model with acute spinal cord injury. METHODS: Microcirculatory changes of acute spinal cord injury were shown by CEUS in a porcine model with spinal cord contusion at three selected time points, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were also obtained by autotracking contrast quantification (ACQ) software in the epicenter of contusion site, adjacent region and distant region, respectively. Neurologic and histologic examinations were used to confirm the severity of injury. RESULTS: Conventional US revealed the spinal cord was hypoechoic and homogeneous, whereas the dura mater, pia mater and cerebral aqueduct were hyperechoic. On CDFI intramedullary blood vessels were displayed as segmental and columnar. It was homogeneous on CEUS. After spinal cord contusion, the injured region on gray scale US was hyperechoic. CDFI demonstrated intramedullary blood vessels of adjacent region had increased and dilated during the observation period. On CEUS the epicenter of contusion site was hypoperfusion, whereas its adjacent region was hyperperfusion compared with the distant region. Quantitative analysis showed that peak intensity decreased in epicenters of contusion but increased in adjacent regions significantly at all time points (P<0.05). Evaluation of neurological function for post-contusion demonstrated significantly deterioration in comparison before injury (P<0.05). CONCLUSIONS: CEUS is a practical technique that provides overall views for evaluating microcirculatory pattern in spinal cord injury. Quantitative analysis shows the efficacy in assessment of perfusion changes after spinal cord injury.


Assuntos
Meios de Contraste , Microcirculação/fisiologia , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Espinal/irrigação sanguínea , Medula Espinal/diagnóstico por imagem , Ultrassonografia Doppler em Cores/normas , Doença Aguda , Animais , Modelos Animais de Doenças , Feminino , Suínos , Ultrassonografia Doppler em Cores/métodos
15.
Neuroscience ; 213: 81-92, 2012 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-22521820

RESUMO

The neuromodulator adenosine maintains brain homeostasis and regulates complex behaviour via activation of inhibitory and excitatory adenosine receptors (ARs) in a brain region-specific manner. AR antagonists such as caffeine have been shown to ameliorate cognitive impairments in animal disease models but their effects on learning and memory in normal animals are equivocal. An alternative approach to reduce AR activation is to lower the extracellular tone of adenosine, which can be achieved by up-regulating adenosine kinase (ADK), the key enzyme of metabolic adenosine clearance. However, mice that globally over-express an Adk transgene ('Adk-tg' mice) were devoid of a caffeine-like pro-cognitive profile; they instead exhibited severe spatial memory deficits. This may be mechanistically linked to cortical/hippocampal N-methyl-d-aspartate receptor (NMDAR) hypofunction because the motor response to acute MK-801 was also potentiated in Adk-tg mice. Here, we evaluated the extent to which the behavioural phenotypes of Adk-tg mice might be modifiable by up-regulating adenosine levels in the cortex/hippocampus. To this end, we investigated mutant 'fb-Adk-def' mice in which ADK expression was specifically reduced in the telencephalon leading to a selective increase in cortical/hippocampal adenosine, while the rest of the brain remained as adenosine-deficient as in Adk-tg mice. The fb-Adk-def mice showed an even greater impairment in spatial working memory and a more pronounced motor response to NMDAR blockade than Adk-tg mice. These outcomes suggest that maintenance of cortical/hippocampal adenosine homeostasis is essential for effective spatial memory and deviation in either direction is detrimental with increased expression seemingly more disruptive than decreased expression.


Assuntos
Adenosina Quinase/metabolismo , Adenosina/metabolismo , Encéfalo/metabolismo , Homeostase/fisiologia , Memória de Curto Prazo/fisiologia , Animais , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Mutantes , Receptores de N-Metil-D-Aspartato/metabolismo
16.
Neoplasma ; 57(6): 501-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20845987

RESUMO

UNLABELLED: Survivin may play an important role in the development of osteosarcoma. In this study, we chose osteosarcoma cell line MG-63, which highly expressed survivin, to observe the effects of antisense oligonucleotide targeting survivin on the apoptosis induction and proliferation inhibition. It was shown in our results that the apoptosis rate and the proliferation inhibition rate increased significantly in survivin-positive cells MG-63 by using MTT and flow cytometry methods. We found that the growth inhibition rate and apoptosis rate were changed in a dose-dependent way. When the concentration of antisurvivin oligonucleotide was 600 nM, the effects reached the peak. RT-PCR and western-blot methods were used to detect the mRNA and protein expression of survivin in MG-63. We observed that the mRNA and protein expression of survivin reduced after transfected with antisurvivin oligonucleotides at the concentration of 200 nM, 400 nM and 600 nM. At the same time, we found that the mRNA and protein expression of Fas were up-regulated with the concentration of antisurvivin oligonucleotides from 200 nM to 600 nM. It was negative associated with the expression change of survivin. These data suggested that survivin should play an important role in the development of osteosarcoma and the survivin blockaded by using antisurvivin oligonucleotide could inhibit the proliferation and induce apoptosis of osteosarcoma by decreasing the expression of survivin and activate the Fas-mediated apoptosis. Down-regulation of survivin by antisense oligonucleotide might be an effective strategy to the treatment of osteosarcoma and might improve the therapeutic effect. KEYWORDS: osteosarcoma, Survivin, apoptosis, Fas.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Ósseas/terapia , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Oligonucleotídeos Antissenso/farmacologia , Osteossarcoma/terapia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose , Proteínas Associadas aos Microtúbulos/análise , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/fisiologia , Osteossarcoma/patologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Survivina
17.
Emerg Med J ; 26(8): 573-5, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19625553

RESUMO

In China the practice of emergency medicine includes patient management in the prehospital, emergency department and intensive care settings. In recent years, emergency medicine has emerged as an independent medical specialty in its own right, and has built up its own professional pool of clinicians, academicians and researchers. There is, however, still much room for improvement compared with developed countries, especially in the areas of clinical and prehospital care, teaching and scientific research. In this paper the current state of emergency medicine education in China is presented and further avenues for improvement are explored.


Assuntos
Educação Médica Continuada/tendências , Educação de Pós-Graduação em Medicina/tendências , Educação de Graduação em Medicina/tendências , Medicina de Emergência/educação , China , Currículo , Educação Médica Continuada/métodos , Educação de Pós-Graduação em Medicina/métodos , Educação de Graduação em Medicina/métodos , Medicina de Emergência/tendências , Ensino/métodos
18.
Neuroscience ; 157(3): 644-55, 2008 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-18848971

RESUMO

Histone deacetylase (HDAC) plays an important role in chromatin remodeling in response to a variety of neurochemical signalings and behavioral manipulations, and may be a therapeutic target for modulation of psychostimulant behavioral sensitization. In this study, we investigated the molecular interaction between histone deacetylase inhibitor (HDACi) and psychostimulant in vivo of mice after repeated treatment with the HDACi, butyric acid (BA) and valproic acid (VPA), alone or in combination with amphetamine. Repeated treatment with amphetamine produced HDACi-like effects: enhanced global histone H4 acetylation level by Western blot as well as specific histone H4 acetylation associated with fosB promoter by chromatin immunoprecipitation in the striatum. Conversely, repeated treatment with BA or VPA produced amphetamine-like effects: enhanced cAMP responsive element binding protein (CREB) phosphorylation at Ser(133) position and increased DeltaFosB protein levels in the striatum. Furthermore, co-administration of BA or VPA with amphetamine produced additive effects on histone H4 acetylation as well as CREB phosphorylation in the striatum. The interplay of HDAC and CREB was also supported by co-immunoprecipitation assays demonstrating that repeated treatment with VPA reduced the association of CREB and HDAC1 in the striatum. Finally, the additive effect of VPA/BA and amphetamine on histone H4 acetylation, phosphorylated CREB, and DeltaFosB was associated with potentiated amphetamine-induced locomotor activity. Thus, HDACi may interact additively with psychostimulants at both histone acetylation and CREB phosphorylation through the CREB:HDAC protein complex in the striatum to modulate DeltaFosB protein levels and psychomotor behavioral sensitization.


Assuntos
Anfetamina/farmacologia , Ácido Butírico/farmacologia , Proteína de Ligação a CREB/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Histonas/metabolismo , Atividade Motora/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ácido Valproico/farmacologia , Acetilação/efeitos dos fármacos , Animais , Imunoprecipitação da Cromatina/métodos , Interações Medicamentosas , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fatores de Tempo
19.
Spinal Cord ; 46(11): 716-21, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18414428

RESUMO

STUDY DESIGN: Experimental laboratory investigations with a model of neurotrauma in Macaca rhesus. OBJECT: The present study evaluates whether intrathecal papaverine induces changes in spinal cord blood flow (SCBF) of injured spinal cord and prevents secondary injury. SETTING: Institute of Spinal Cord Injury, Sun Yat-sen University, China. METHODS: After laminectomy was performed and contusive spinal cord injuries were induced in adult female Macaca rhesus, three received intrathecal papaverine, and three received saline 0.9% for control. SCBF was registered by laser-Doppler recording technique continuously for 180 min after injection. Histological analyses and microvessel density (MVD) were used for evaluation of spinal cord injury, and the percentage of spared spinal cord area was calculated. RESULTS: Mean arterial blood pressure showed no significant change in both groups. In the papaverine group, SCBF recovered to 81.35+/-7.8% of baseline at 15 min, 75.24+/-6.3% at 30 min, 73.38+/-2.3% at 90 min and 72.57+/-4.1% at 180 min after the completion of infusion. SCBF was significantly higher than the control groups (P<0.01). There was no occlusion of the arteries, but occluded veins were identified at the injured site. The MVD in the spinal cord of the control group was significantly lesser than the papaverine group (P<0.01). Luxol Fast Blue staining showed that intrathecal papaverine reduced myelin loss in the lesion 2 weeks after injury (P<0.05). CONCLUSION: Intrathecal administration of papaverine increased SCBF in non-human primates. It is likely that the effects of papaverine can reduce secondary injury in spinal cord injured Macaca rhesus.


Assuntos
Microvasos/efeitos dos fármacos , Papaverina/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Injeções Espinhais , Laminectomia/métodos , Fluxometria por Laser-Doppler/métodos , Macaca mulatta , Microvasos/patologia , Microvasos/fisiopatologia , Papaverina/administração & dosagem , Medula Espinal/irrigação sanguínea , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico
20.
J Pept Res ; 65(1): 143-8, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15686545

RESUMO

In order to extend the use of proteases to organic synthesis and seek the rules of enzymatic reactions in organic media, we focused on unnatural substrates for proteases to form amide bonds. In this paper, the study of unnatural substrates containing D-amino acid residue, which act as acyl acceptors as well as acyl donors for proteases in organic media, is reported. Dermorphin is a heptapeptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) with potent analgesic activity. The N-terminal tetrapeptide is the minimum sequence that retains dermorphin activity, and is selected as the model compound in our study. Two dermorphin-(1-4) derivatives, Boc-Tyr-D-Ala-Phe-Gly-N(2)H(2)Ph and Boc-Tyr-D-Ala-Phe-Gly-NH(2), which contained a d-amino acid residue, were synthesized by proteases in organic media for the first time. The synthesis of these two dermorphin-(1-4) derivatives could be catalyzed by subtilisin with Boc-Tyr-D-Ala-OCH(2)CF(3) as an acyl donor substrate in AcOEt. The synthesis of dermorphin-(1-2) derivative Boc-Tyr-D-Ala-N(2)H(2)Ph was catalyzed by alpha-chymotrypsin in different organic solvents and D-Ala-N(2)H(2)Ph was used as an acyl acceptor substrate. Factors influencing the above enzymatic reactions were systematically studied.


Assuntos
Quimotripsina/metabolismo , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Compostos Orgânicos/metabolismo , Solventes/metabolismo , Subtilisina/metabolismo , Catálise , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Peptídeos Opioides
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA