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2.
Medicine (Baltimore) ; 97(41): e12455, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30313035

RESUMO

BACKGROUND: Digestive system cancers are recognized as associated with high morbidity and mortality. It is generally accepted that N-myc downstream-regulated gene 1 (NDRG1) is aberrantly overexpressed or downregulated in digestive system cancers, and its prognostic value remains controversial. Accordingly, we herein conducted a meta-analysis to explore whether NDRG1 expression is correlated with overall survival (OS) and clinicopathological characteristics of patients with digestive system cancers. METHODS: We systematically searched PubMed, EMBASE, and Web of Science for eligible studies up to June 6, 2017. In all, 19 publications with 21 studies, were included. RESULTS: The pooled results showed that low NDRG1 expression was significantly associated with worse OS in colorectal cancer (pooled HR = 1.67, 95% CI: 1.22-2.28, P < .001) and pancreatic cancer (pooled HR = 1.87, 95% CI: 1-3.5, P < .0001). Moreover, the relationships between low NDRG1 expression and higher OS ratio of patients with liver cancer (pooled HR = 0.44, 95% CI: 0.32-0.62, P = .009) and gallbladder cancer (pooled HR = 0.56, 95% CI: 0.23-1.38, P = .01) were observed. Nevertheless, no significant association was observed between low NDRG1 expression and OS in gastric cancer (pooled HR = 0.81, 95% CI: 0.45-1.43, P = .46) or esophageal cancer (pooled HR = 0.76, 95% CI: 0.26-2.24, P = .62). CONCLUSION: The prognostic significance of NDRG1 expression varies according to cancer type in patients with DSCs. Considering that several limitations existed in this meta-analysis, more studies are required to further assess the prognostic value of NDRG1 expression in patients with DSCs and relevant mechanisms.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/mortalidade , Proteínas de Ciclo Celular/metabolismo , Neoplasias do Sistema Digestório/diagnóstico , Neoplasias do Sistema Digestório/mortalidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Carcinoma/metabolismo , Neoplasias do Sistema Digestório/metabolismo , Regulação para Baixo , Humanos , Prognóstico , Análise de Sobrevida , Regulação para Cima
3.
Zhongguo Zhong Yao Za Zhi ; 42(16): 3206-3212, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29171242

RESUMO

Tongmai formula (TMF) is a drug combination of three components including Puerariae Lobatae Radix [roots of Pueraria lobata], Salviae Miltiorrhizae Radix (roots of Salvia miltiorrhiza) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong) in a weight ratio of 1∶1∶1. The absorption and transport of isoflavonoid compounds from Tongmai formula across human intestinal epithelial (Caco-2) cells in vitro were studied in this paper. The assay isoflavonoid compounds include daidzein, formononetin, 5-hydroxylononin, ononin, daidzin, 3'-methoxypuerarin, genistin, puerarin, formononetin-8-C-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside, formononetin-7-O-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside, lanceolarin, kakkanin, daidzein-7,4'-di-O-ß-D-glucopyranoside, mirificin, 3'-hydroxypuerarin, 3'-methoxydaidzin, formononetin-8-C-ß-D-xylopyranosyl-(1→6)-O-ß-D-glucopyranoside, genistein-8-C-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside, genistein-7-O-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside (ambocin), 3'-hydroxymirificin, 6″-O-ß-D-xylosylpuerarin, biochanin A-8-C-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside, 3'-methoxydaidzein-7,4'-di-O-ß-D-glucopyranoside, daidzein-7-O-ß-D-glucopyranosyl-(1→4)-O-ß-D-glucopyranoside, and daidzein-7-O-α-D-glucopyranosyl-(1→4)-O-ß-D-glucopyranoside. By using human Caco-2 monolayer as an intestinal epithelial cell model in vitro, the permeability of above-mentioned 25 isoflavonoids in TMF were studied from the apical (AP) side to basolateral (BL) side or from the BL side to AP side. The assay compounds were determined by reversed phased high-performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apparent permeability coefficients (Papp) were then calculated and and compared with those of propranolol and atenolol, which are the transcellular transport marker and as a control substance for high and poor permeability, respectively. The Papp values of daidzein and formononetin were (2.55±0.03) ×10⁻5,(3.06±0.01) ×10⁻5 cm•s⁻¹ from AP side to BL side, respectively, and (2.62±0.00) ×10⁻5, (2.65±0.11) ×10⁻5 cm•s⁻¹ from BL side to AP side, respectively. Under the condition of this experiment, the Papp value was (2.66±0.32) ×10⁻5 cm•s⁻¹ for propranolol and (2.34±0.10) ×10⁻7 cm•s⁻¹ for atenolol. The Papp values of daidzein and formononetin were at a same magnitude with those of propranolol. And the Papp values of other 23 isoflavonoid compounds were at a same magnitude with those of atenolol. On the other hand, the rats of Papp AP→BL/Papp BL→AP of daidzein and formononetin on the influx transport were 0.97 and 1.15, respectively. It can be predicted that daidzein and formononetin can be absorbed across intestinal epithelial cells to go to the body circulation by the passive diffusion mechanism and they were assigned to the well-absorbed compounds. Other 23 isoflavonoid compounds were assigned to the poorly absorbed compounds. Because of the rats of Papp AP→BL/Papp BL→AP of 5-hydroxylononin, genistin, lanceolarin, kakkanin, and genistein-7-O-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside were 0.18, 0.28, 0.45, 0.38, 0.49, they may have been involved in the efflux mechanism in Caco-2 cells monolayer model from the BL side to AP side direction.

4.
World J Gastroenterol ; 23(33): 6119-6127, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28970727

RESUMO

AIM: To investigate the molecular mechanisms of gastric carcinogenesis. METHODS: We used label-free quantification technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in 160 specimens of normal gastric mucosa, gastric mucosa with mild dysplasia, moderate dysplasia, severe dysplasia, and early mucosal gastric cancer (GC) collected at the Second Hospital of Lanzhou University from 2010 to 2015. Immunohistochemistry was used to verify the differentially expressed proteins detected by LC-MS/MS. RESULTS: With a threshold of a 1.2-fold change and a P-value < 0.05 between mild dysplasia, moderate dysplasia, severe dysplasia or early mucosal GC and matched normal gastric mucosa tissues, proteomic analysis identified 365 significantly differentially expressed proteins. ERGIC1 expression decreased, while DNA-PKcs expression increased gradually along with different stages of GC initiation based on the tendency of fold change. The expression patterns of ERGIC1 and DNA-PKcs revealed by immunohistochemistry were consistent with the LC-MS/MS results. CONCLUSION: The results suggest that aberrant ERGIC1 and DNA-PKcs expression may be involved in GC initiation.


Assuntos
Carcinogênese/patologia , Diferenciação Celular , Proteína Quinase Ativada por DNA/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Proteínas de Transporte Vesicular/metabolismo , Adulto , Idoso , Cromatografia Líquida de Alta Pressão/métodos , Regulação para Baixo , Feminino , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Regulação para Cima
5.
BMJ Open ; 7(8): e016481, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28860228

RESUMO

INTRODUCTION: Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as 'tension' repair or 'tension-free' repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. METHODS AND ANALYSIS: This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). ETHICS AND DISSEMINATION: This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015-027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: NCT02984917; preresults.


Assuntos
Hérnia Inguinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Adulto Jovem
6.
Molecules ; 22(4)2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28353641

RESUMO

Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and convenient analytical method for a comprehensive determination of polyphenols in TMF and the ascertainment of their chemical correlations with its herbal components, a method combining high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for rapid determination of 30 polyphenols in TMF and its three herbal components. The chromatographic separation was carried out on a Chromolith Fastgradient RP-18 endcapped 50-2 column using an optimized gradient elution. Statistical analysis of obtained data demonstrated that the method had a desirable linearity, precision, and accuracy, as well as excellent sensitivity. The obtained results indicated that, among the 30 polyphenols in TMF, 22 originated from Gegen, 6 originated from Danshen, and 2 originated from Chuanxiong. The major polyphenols in TMF have been identified as puerarin, mirificin, salvianolic acid B, salvianic acid A, 3'-hydroxypuerarin, 3'-methoxypuerarin, and salvianolic acid A, with a combined contribution of 19.2% of the preparation. The development and validation of this method will greatly facilitate future pharmacological studies of TMF and its herbal components, as well as polyphenols in cardiovascular therapies.


Assuntos
Medicamentos de Ervas Chinesas/química , Polifenóis/análise , Cromatografia Líquida de Alta Pressão/métodos , Estrutura Molecular , Extratos Vegetais/análise , Polifenóis/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
7.
Molecules ; 20(10): 18704-16, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26501241

RESUMO

Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and intestinal absorption deserves study. In this work TMF extract was incubated with human intestinal bacteria under anaerobic conditions and the changes in the twelve main constituents of TMF were then investigated. Their intestinal permeabilities, i.e., the transport capability across the intestinal brush border were investigated with a human colon carcinoma cell line (Caco-2) cell monolayer model to predict the absorption mechanism. Meanwhile, rapid HPLC-DAD methods were established for the assay. According to the biotransformation curves of the twelve constituents and the permeability coefficients, the intestinal absorption capacity of the typical compounds was elevated from the levels of 10(-7) cm/s to 10(-5) cm/s from those of the original compounds in TMF. Among them the main isoflavone glycosides puerarin (4), mirificin (6) and daidzin (7) were transformed into the same aglycone, daidzein (10). Therefore it was predicted that the aglycone compounds might be the real active ingredients in TMF. The models used can represent a novel path for the TCM studies.


Assuntos
Bactérias/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Microbioma Gastrointestinal/fisiologia , Isoflavonas/biossíntese , Consórcios Microbianos/fisiologia , Atenolol/metabolismo , Transporte Biológico , Biotransformação , Células CACO-2 , Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Fezes/microbiologia , Humanos , Isoflavonas/isolamento & purificação , Isoflavonas/metabolismo , Medicina Tradicional Chinesa , Permeabilidade , Propranolol/metabolismo
8.
World J Gastroenterol ; 21(33): 9785-92, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26361426

RESUMO

AIM: To evaluate the accuracy of diffusion-weighted imaging (DWI) without bowel preparation, the optimal b value and the changes in apparent diffusion coefficient (ADC) in detecting ulcerative colitis (UC). METHODS: A total of 20 patients who underwent 3T magnetic resonance imaging (MRI) without bowel preparation and colonoscopy within 24 h were recruited. Biochemical indexes, including C-reactive protein (CRP), erythrocyte sedimentation rate, hemoglobin, leucocytes, platelets, serum iron and albumin, were determined. Biochemical examinations were then performed within 24 h before or after MR colonography was conducted. DWI was performed at various b values (b = 0, 400, 600, 800, and 1000 s/mm(2)). Two radiologists independently and blindly reviewed conventional- and contrast-enhanced MR images, DWI and ADC maps; these radiologists also determined ADC in each intestinal segment (rectum, sigmoid, left colon, transverse colon, and right colon). Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of DWI hyperintensity from various b factors, ADC values and different radiological signs to detect endoscopic inflammation in the corresponding bowel segment. Optimal ADC threshold was estimated by maximizing the combination of sensitivity and specificity. MR findings were correlated with endoscopic results and clinical markers; these findings were then estimated by ROC analysis. RESULTS: A total of 100 segments (71 with endoscopic colonic inflammation; 29 normal) were included. The proposed total magnetic resonance score (MR-score-T) was correlated with the total modified Baron score (Baron-T; r = 0.875, P < 0.0001); the segmental MR score (MR-score-S) was correlated with the segmental modified Baron score (Baron-S; r = 0.761, P < 0.0001). MR-score-T was correlated with clinical and biological markers of disease activity (r = 0.445 to 0.831, P < 0.05). MR-score-S > 1 corresponded to endoscopic colonic inflammation with a sensitivity of 85.9%, a specificity of 82.8% and an area under the curve (AUC) of 0.929 (P < 0.0001). The accuracy of DWI hyperintensity was significantly greater at b = 800 than at b = 400, 600, or 1000 s/mm(2) (P < 0.05) when endoscopic colonic inflammation was detected. DWI hyperintensity at b = 800 s/mm(2) indicated endoscopic colonic inflammation with a sensitivity of 93.0%, a specificity of 79.3% and an AUC of 0.867 (P < 0.0001). Quantitative analysis results revealed that ADC values at b = 800 s/mm(2) differed significantly between endoscopic inflamed segment and normal intestinal segment (1.56 ± 0.58 mm(2)/s vs 2.63 ± 0.46 mm(2)/s, P < 0.001). The AUC of ADC values was 0.932 (95% confidence interval: 0.881-0.983) when endoscopic inflammation was detected. The threshold ADC value of 2.18 × 10(-3) mm(2)/s indicated that endoscopic inflammation differed from normal intestinal segment with a sensitivity of 89.7% and a specificity of 80.3%. CONCLUSION: DWI combined with conventional MRI without bowel preparation provides a quantitative strategy to differentiate actively inflamed intestinal segments from the normal mucosa to detect UC.


Assuntos
Colite Ulcerativa/patologia , Colo/patologia , Imagem de Difusão por Ressonância Magnética , Mucosa Intestinal/patologia , Área Sob a Curva , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colonoscopia , Meios de Contraste , Gadolínio DTPA , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes
9.
J Neurooncol ; 124(1): 5-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25968345

RESUMO

Baicalein, a widely used Chinese herbal medicine, has been proved as a promising chemopreventive compound for many cancers. The aim of this work was to assess the anti-tumor effect of baicalein in the orthotopic glioma models. It was found that treatment of mice with U87 gliomas with baicalein (20 and 40 mg/kg/day, i.p.) significantly inhibited the intracerebral tumor growth and prolonged the survival. Furthermore, treatment with baicalein suppressed cell proliferation, promoted apoptosis, and arrested cell cycle in U87 gliomas. In addition, treatment with baicalein reduced tumor permeability, attenuated edema of tumors and brains, and improved tight junctions in gliomas. Finally, treatment with baicalein reduced the expression of HIF-1α, VEGF, and VEGFR2 in U87 gliomas. In addition, treatment with baicalein also markedly suppressed tumor growth and prolonged the survival of rats with 9L gliomas. In conclusion, baicalein has an obvious anti-tumor activity in the orthotopic glioma models. Our results suggested that treatment with baicalein might be an effective therapy for recurrent malignant brain cancers through suppressing tumor growth and alleviating edema.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Flavanonas/administração & dosagem , Glioma/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Peso Corporal/efeitos dos fármacos , Edema Encefálico/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Claudina-1/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Ratos , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-25821488

RESUMO

Recently µ opioid receptor (MOR) has been shown to be closely associated with depression. Here we investigated the action of Shuyu, a Chinese herbal prescription, on repeated restraint stress induced depression-like rats, with specific attention to the role of MOR and the related signal cascade. Our results showed that repeated restraint stress caused significant depressive-like behaviors, as evidenced by reduced body weight gain, prolonged duration of immobility in forced swimming test, and decreased number of square-crossings and rearings in open field test. The stress-induced depression-like behaviors were relieved by Shuyu, which was accompanied by decreased expression of MOR in hippocampus. Furthermore, Shuyu upregulated BDNF protein expression, restored the activity of CREB, and stimulated MEK and ERK phosphorylation in hippocampus of stressed rats. More importantly, MOR is involved in the effects of Shuyu on these depression-related signals, as they can be strengthened by MOR antagonist CTAP. Collectively, these data indicated that the antidepressant-like properties of Shuyu are associated with MOR and the corresponding CREB, BDNF, MEK, and ERK signal pathway. Our study supports clinical use of Shuyu as an effective treatment of depression and also suggests that MOR might be a target for treatment of depression and developing novel antidepressants.

11.
Int J Mol Sci ; 16(3): 5750-61, 2015 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-25775156

RESUMO

Plant-associated microorganisms are known to produce a variety of metabolites with novel structures and interesting biological activities. An endophytic fungus FJBJ11, isolated from the plant tissue of Brucea javanica (L.) Merr. (Simaroubaceae), was proven to be significantly effective in producing metabolites with anti-Tobacco mosaic virus (TMV) activities. The isolate was identified as Aspergillus tubingensis FJBJ11 based on morphological characteristics and ITS sequence. Bioassay-guided isolation led to the identification of a cycli penta-peptide, malformin A1, along with two cyclic dipeptides, cyclo (Gly-L-Pro) and cyclo (Ala-Leu). Malformin A1 showed potent inhibitory effect against the infection and replication of TMV with IC50 values of 19.7 and 45.4 µg·mL⁻¹, as tested using local lesion assay and leaf-disc method, respectively. The results indicated the potential use of malformin A1 as a leading compound or a promising candidate of new viricide.


Assuntos
Aspergillus/metabolismo , Peptídeos Cíclicos/metabolismo , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Brucea/microbiologia , Espectroscopia de Ressonância Magnética , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Filogenia , Estrutura Secundária de Proteína , Vírus do Mosaico do Tabaco/efeitos dos fármacos
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 31(4): 329-31, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26775503

RESUMO

OBJECTIVE: The aim of this study is to investigate the occurrence and mechanism of Cheyne-Stokes breathing pattern in patients with heart failure. METHODS: Fifty-six patients who performed polusomnography sleep testing at National Center of Cardiovascular Diseases Fuwai Hospital from March to May in 2015. We divided them into chronic heart failure (CHF) group and non-CHF group. RESULTS: The occurrences of sleep apnea in two groups were high. In CHF group (n = 11) , there were 10 patients with apnea hypopnea index (AHI) > 5; and their AHI was 23.93 ±14.63. In non-CHF group (n = 45), there were 33 patients whose AHI > 5; and their AHI was 16.20 ± 18.76. The ratio of center sleep apnea to all gross sleep apnea ratio in CHF group was higher than that in non-CHF group (80.21% ± 30.55% vs 27.16% ± 35.71%, P < 0.01 ). CONCLUSION: Based upon the new theory of holistic integrative physiology and medicine, we explain the mechanism of circulatory dysfunction induce the oscillation breathing in patients with CHF. The sleep apnea and C-S respiration in CHF should be called circulatory sleep apnea, rather than central sleep apnea.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Respiração de Cheyne-Stokes , Doença Crônica , Humanos , Polissonografia , Apneia do Sono Tipo Central
13.
Acta Pharmacol Sin ; 35(12): 1556-65, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25399650

RESUMO

AIM: Probucol, an anti-hyperlipidemic drug, has been reported to exert antitumor activities at various stages of tumor initiation, promotion and progression. In this study we examined whether the drug affected glioma cell growth in vitro and the underlying mechanisms. METHODS: Human glioma U87 and glioblastoma SF295 cell lines were used. Cell proliferation was accessed using the cell proliferation assay and BrdU incorporation. The phosphorylation of AMPK, liver kinase B1 (LKB1) and p27(Kip1) was detected by Western blot. The activity of 26S proteasome was assessed with an in situ fluorescent substrate. siRNAs were used to suppress the expression of the relevant signaling proteins. RESULTS: Treatment of U87 glioma cells with probucol (10-100 µmol/L) suppressed the cell proliferation in dose- and time dependent manners. Meanwhile, probucol markedly increased the ROS production, phosphorylation of AMPK at Thr172 and LKB1 at Ser428 in the cells. Furthermore, probucol significantly decreased 26S proteasome activity and increased p27(Kip1) protein level in the cells in an AMPK-dependent manner. Probucol-induced suppression of U87 cell proliferation could be reversed by pretreatment with tempol (a superoxide dismutase mimetic), MG132 (proteasome inhibitor) or compound C (AMPK inhibitor), or by gene silencing of LKB1, AMPK or p27(Kip1). Similar results were observed in probucol-treated SF295 cells. CONCLUSION: Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation, which reduces 26S proteasome-dependent degradation of p27(Kip1).


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Glioma/patologia , Estresse Oxidativo/efeitos dos fármacos , Probucol/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Glioma/enzimologia , Glioma/genética , Humanos , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transfecção
14.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 165-171, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710926

RESUMO

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.


Assuntos
Edema Encefálico/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Adulto , Idoso , Edema Encefálico/mortalidade , Edema Encefálico/patologia , Edema Encefálico/cirurgia , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Hemorragia Cerebral/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Food Funct ; 5(1): 123-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24292561

RESUMO

Iron deficiency anemia (IDA) is the one of the most common nutritional problems and is encountered all over the world. This study analysed the effects of squid ink melanin-Fe (SM-Fe) on IDA in rats. Forty weanling SD male rats were used and thirty-two rats were fed an iron-deficient diet for 4 weeks. Then SM-Fe (dosages of iron is 6 mg kg(-1) BW) was given to the IDA rats once a day for 3 weeks by intragastric administration, with FeCl3 and FeSO4 (dosages of iron is 6 mg kg(-1) BW) as positive controls. While the IDA model group and the control group were administrated distilled deionized water each day for 3 weeks. The content of haemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC), serum ferritin (SF), transferrin receptor (sTfR), erythropoietin (EPO), and iron content in the liver and spleen were measured. The results showed that the content of Hb, SI, SF, EPO, iron content in the liver and spleen were significantly increased in the iron supplement groups (SM-Fe, FeCl3 and FeSO4) compared with the model group (P < 0.05), while TIBC and sTfR were significantly decreased in the iron supplement groups compared with the model group (P < 0.05). In comparison with the FeCl3 and FeSO4 groups, a higher bioavailability of iron and fewer side effects were observed in the SM-Fe group. The present study indicated that SM-Fe is an effective source of iron supplement for IDA rats and might be exploited as a new iron fortifier.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Ferro/sangue , Melaninas/administração & dosagem , Anemia Ferropriva/metabolismo , Animais , Decapodiformes , Ferritinas/sangue , Hemoglobinas/metabolismo , Humanos , Masculino , Melaninas/química , Ratos , Ratos Sprague-Dawley , Receptores da Transferrina/metabolismo
16.
Acta Pharmacol Sin ; 35(1): 65-73, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24241350

RESUMO

AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.


Assuntos
Proliferação de Células/efeitos dos fármacos , Diosgenina/uso terapêutico , Modelos Animais de Doenças , Doença de Graves/tratamento farmacológico , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Animais , Diosgenina/farmacologia , Feminino , Bócio/tratamento farmacológico , Bócio/patologia , Doença de Graves/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória
17.
J Neurooncol ; 114(1): 25-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23703297

RESUMO

Regardless of their cell type of origin, all aggressive brain tumors, such as malignant gliomas and metastatic tumors produce brain edema, which is an important cause of patient morbidity and mortality. Caloric restriction (CR) has long been recognized as a natural therapy that improves health, promotes longevity, and significantly reduces both the incidence and growth of many tumor types. The aim of present work was to investigate the effect of CR on edema and survival in the mice implanted with U87 gliomas. We found that CR significantly inhibited the intracerebral tumor growth, attenuated brain edema, and ultimately prolonged survival of mice with U87 gliomas. Plasma corticosterone level was found higher and serum VEGF and IGF-1 levels were found lower in CR, when compared to AL group. CR upregulated tight junction proteins including claudin-1, claudin-5 and ZO-1, downregulated VEGF and VEGFR2, enhanced α-SMA expression, and reduced AQP1 expression in U87 gliomas. In addition, CR suppressed inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) formation in U87 gliomas. In conclusion, CR attenuated edema in U87 orthotopic mouse glioma model associated with elevation of corticosterone, suppression of VEGF/VEGFR2, improvement of tight junctions, and suppression of iNOS expression and NO formation. Our results suggested that CR might be an effective therapy for recurrent malignant brain cancers through alleviating associated edema.


Assuntos
Edema Encefálico/etiologia , Neoplasias Encefálicas , Restrição Calórica/métodos , Glioma , Ácido 3-Hidroxibutírico/sangue , Animais , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/sangue , Glioma/complicações , Glioma/mortalidade , Glioma/terapia , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Ácido Láctico/sangue , Masculino , Camundongos , Nitratos/metabolismo , Permeabilidade , Estatísticas não Paramétricas , Análise de Sobrevida , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/sangue
18.
Appl Microbiol Biotechnol ; 97(16): 7253-64, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23208613

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to be a promising anticancer agent because its active form TRAIL trimer is able to induce apoptosis in different tumor cell lines while sparing normal cells. However, TRAIL trimer possesses a short half-life and low stability, which turns out to be a major obstacle for the development of clinical trials. In our present study, we constructed a recombined TRAIL trimer by genetic fusion of non-collagenous domain (NC1) of human collagen XVIII or its trimerization domain (TD) to C-terminus of TRAIL via a flexible linker, and then refolded the fusion proteins using a two-step refolding approach, namely a combination of dilution and gel filtration chromatography. As a result, both recombinant proteins, TRAIL-NC1 and TRAIL-TD, were expressed in Escherichia coli as inclusion bodies, and they exhibited difficultly to refold efficiently by conventional methods. Thereby, we applied a modified two-step refolding approach to refold fusion proteins. More than 55 % of TRAIL-NC1 and 90 % of TRAIL-TD protein activity was recovered during the two-step refolding approach, and their stability was also increased significantly. Also, size exclusion chromatography showed refolded TRAIL-NC1 was a trimer while TRAIL-TD, hexamer. However, both of them exerted good apoptosis activity on NCI-H460 cells.


Assuntos
Colágeno Tipo XVIII/metabolismo , Dobramento de Proteína , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Cromatografia em Gel , Colágeno Tipo XVIII/genética , Colágeno Tipo XVIII/isolamento & purificação , Colágeno Tipo XVIII/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Escherichia coli/genética , Expressão Gênica , Humanos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/isolamento & purificação , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(9): 1275-9, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23185774

RESUMO

OBJECTIVE: To observe the effects of Jingqianping Granule (JG) on mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus of premenstrual syndrome (PMS) Gan-qi invasion rats. METHODS: Twenty rats were selected to prepare the PMS Gan-qi invasion model. After modeling rats were divided into the model group and the Chinese herb treated group, ten in each group. Another 10 rats were selected as the normal control group. During the modeling, JG (1.6 g/kg) was given to rats in the Chinese herb treated group by gastrogavage, while equal volume of normal saline (1 mL/100 g) was given to rats in normal control group and the model group. All treatment was performed once daily for five successive days. The mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus were detected using RT-PCR and Western blot respectively. RESULTS: Compared with the normal control group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively weaker in the model group, and the optical density value decreased. The MOR mRNA and protein expressions in the parietal cortex and the frontal cortex relatively decreased. But the bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively stronger and optic value increased. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively increased with statistical difference (P<0.01, P<0.05). Compared with the model group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively enhanced, the MOR mRNA expression in the parietal cortex increased, the MOR protein expression in the parietal cortex and the frontal cortex increased in the Chinese herb treated group. The bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively weaker. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively decreased. The MOR protein expression in the hippocampus decreased relatively with statistical difference (P<0.01, P<0.05). CONCLUSIONS: Expression of mu opioid receptor in brains of PMS Gan-qi invasion rats was regionally specific. Administration of JG showed corresponding regulatory effects.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Síndrome Pré-Menstrual/metabolismo , Receptores Opioides mu/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Síndrome Pré-Menstrual/tratamento farmacológico , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/genética
20.
Phytochem Anal ; 23(6): 647-50, 2012 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22552877

RESUMO

INTRODUCTION: Cotton is an important economic crop. Genetic, developmental and molecular studies of cotton require high-quality total RNA from different tissues. Due to the richness in polyphenols and polysaccharides, the Trizol-based methods and other commercial kits are unsuitable for RNA isolation from cotton. Available methods are generally laborious and time-consuming. OBJECTIVE: To develop an easy, simple and rapid cetyltrimethylammonium bromide (CTAB)-ammonium acetate protocol that takes less time and obtains high yield and quality of RNA from polysaccharide- and polyphenol-rich cotton tissues. METHODOLOGY: Based on the original CTAB protocol, we used phenol-chloroform and chloroform-isoamyl alcohol to remove proteins, polysaccharides and polyphenols, and ammonium acetate to precipitate RNA, reducing the incubation time prior to RNA precipitation. After adding ammonium acetate to precipitate RNA, all centrifugation steps (14000 × g) were carried out at 4°C to avoid degradation. RESULTS: The procedure took only 1.5 h and was suitable for different cotton tissues. The A(260) : A(280) ratios ranged from 1.80 to 1.85 with clear 28 s and 18 s ribosomal RNA bands in 1.2% agarose gel. The isolated RNA was usable for downstream molecular studies, such as reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR. CONCLUSION: The CTAB-ammonium acetate method is easy, rapid, low-cost and effective for high-quality RNA isolation from polysaccharide- and polyphenol-rich cotton tissues.


Assuntos
Acetatos/química , Compostos de Cetrimônio/química , Gossypium/genética , RNA de Plantas/isolamento & purificação , Cetrimônio , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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