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1.
J Dig Dis ; 20(6): 278-287, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31090180

RESUMO

OBJECTIVES: Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. METHODS: Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. RESULTS: Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. CONCLUSION: The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30396213

RESUMO

OBJECTIVE: To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). METHODS: In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients' data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. RESULTS: BMD at every location tested (femoral neck, trochanter, inside hip, Ward's triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (ß-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or ß-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and ß-CTX (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-29849732

RESUMO

Objective. Panax ginseng is widely used for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of Panax ginseng. This study aimed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury in rats. Methods. Male Wistar rats were orally given Ginsenoside Re (5, 20 mg/kg) daily for 7 days. Isoproterenol was subcutaneously injected into the rats for two consecutive days at a dosage of 20 mg/kg/day (on 6th and 7th day). Six hours after the last isoproterenol injection, troponin T level and creatine kinase-MB (CK-MB) activity were assayed. Histopathological examination of heart tissues was performed. The levels of malondialdehyde (MDA) and glutathione (GSH) in heart tissues were measured. The nuclear factor erythroid 2-related factor 2 (Nrf2) content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit (GCLC) and glutathione cysteine ligase modulatory subunit (GCLM) in heart tissues were assayed by western blotting method. Results. Treatment with Ginsenoside Re at dose of 5, 20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol. The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis and inflammatory cells infiltration. Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues. Moreover, the Nrf2 content in nucleus and the expressions of GCLC and GCLM were significantly increased in the animals treated with Ginsenoside Re. Conclusion. These findings suggested that Ginsenoside Re possesses the property to attenuate isoproterenol-induced myocardial ischemic injury by regulating the antioxidation function in cardiomyocytes.

4.
J Cancer ; 9(9): 1548-1559, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760792

RESUMO

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer death in the world and has a notably low survival rate. Circular RNAs (circRNAs) are newly classed non-coding RNA (ncRNA) members that are capable of regulating gene expression at transcription or post-transcription levels. Recent studies demonstrate that some circRNAs are differentially expressed in HCC, and the deregulation of these circRNAs is associated with the clinical pathological and prognostic significance. They also play essential roles in HCC progression, and contribute to cell proliferation, migration, invasion and metastasis by targeting different microRNAs (miRNAs) and protein-coding genes. In this review, we concentrate on recent progress of some important circRNAs in HCC, with an emphasis on their deregulation, functions and regulatory mechanisms, and discuss their potential utility as diagnostic and/or prognostic biomarkers or therapeutic targets for HCC.

5.
Int J Mol Sci ; 19(4)2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29614812

RESUMO

20(S)-Protopanaxadiol (PPD) is one of the major active metabolites of ginseng. It has been reported that 20(S)-PPD shows a broad spectrum of antitumor effects. Our research study aims were to investigate whether apoptosis of human breast cancer MCF-7 cells could be induced by 20(S)-PPD by targeting the Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway in vitro and in vivo. Cell cycle analysis was performed by Propidium Iodide (PI) staining. To overexpress and knock down the expression of mTOR, pcDNA3.1-mTOR and mTOR small interfering RNA (siRNA) transient transfection assays were used, respectively. Cell viability and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test and Annexin V /PI double-staining after transfection. The antitumor effect in vivo was determined by the nude mice xenograft assay. After 24 h of incubation, treatment with 20(S)-PPD could upregulate phosphorylated-Phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) expression and downregulate PI3K/AKT/mTOR-pathway protein expression. Moreover, G0/G1 cell cycle arrest in MCF-7 cells could be induced by 20(S)-PPD treatment at high concentrations. Furthermore, overexpression or knockdown of mTOR could inhibit or promote the apoptotic effects of 20(S)-PPD. In addition, tumor volumes were partially reduced by 20(S)-PPD at 100 mg/kg in a MCF-7 xenograft model. Immunohistochemical staining indicated a close relationship between the inhibition of tumor growth and the PI3K/AKT/mTOR signal pathway. PI3K/AKT/mTOR pathway-mediated apoptosis may be one of the potential mechanisms of 20(S)-PPD treatment.


Assuntos
Apoptose/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sapogeninas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos
6.
Artigo em Inglês | MEDLINE | ID: mdl-28229049

RESUMO

Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of the Picornaviridae family, EV-A71, differs from EV-D68 in that G0/G1 synchronization inhibits, rather than promotes, EV-A71 viral replication. However, these viruses are similar in that G2/M synchronization inhibits the production and activity of both viruses, which is suggestive of a common therapeutic target for both types of enterovirus. These results further clarify the pathogenic mechanisms of enteroviruses and provide a potential strategy for the treatment and prevention of EV-D68-related disease.


Assuntos
Ciclo Celular , Enterovirus Humano D/fisiologia , Infecções por Enterovirus/virologia , Replicação Viral , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Células Cultivadas , Interações Hospedeiro-Patógeno , Humanos
7.
Artigo em Inglês | MEDLINE | ID: mdl-28105061

RESUMO

Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1ß in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1ß in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation.

8.
Zhong Yao Cai ; 39(1): 11-5, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30079697

RESUMO

Objective: In order to provide the theoretical basis for the Guangfeng medicinal yam( Dioscorea opposita) in field transplanting, the effect of PEG-6000 simulation drought stress on physiological characteristics of Guangfeng medicinal yam plantlets was studied. Methods: Using the method of spectrophotometer,the content of total chlorophyll,soluble total sugar, soluble protein and praline,as well as the activities of SOD,CAT and POD of Guangfeng medicinal yam plantlets were tested under PEG-6000 treatment. Results: Under PEG-6000 simulated drought stress, with the increasing of drought stress and the extension of stress time, the total chlorophyll content of Guangfeng medicinal yam plantlets continued to decline, the content of total soluble sugar, proline and MDA of Guangfeng medicinal yam plantlets significantly increased, the content of soluble protein and the activities of CAT,POD and SOD of Guangfeng medicinal yam plantlets increased at first and then decreased. Conclusion: This study reveals the changes of physiological indices of Guangfeng medicinal yam plantlets under PEG-6000 simulation drought stress, which indicated that Guangfeng medicinal yam plantlets have certain drought tolerance.


Assuntos
Dioscorea , Secas , Clorofila , Polietilenoglicóis , Prolina , Estresse Fisiológico
9.
World J Gastroenterol ; 21(12): 3706-10, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25834339

RESUMO

AIM: To assess the prognostic value of c-Met status in colorectal cancer. METHODS: We conducted a search in PubMed, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0. RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios (HR) indicated that patients with high c-Met expression have a significantly poorer overall survival (OR) (HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival (PFS) (HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported (HR = 1.41, 95%CI: 1.08-1.74). CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/enzimologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Humanos , Razão de Chances , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Regulação para Cima
10.
World J Gastroenterol ; 20(41): 15398-412, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25386090

RESUMO

AIM: To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and the bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to fish intake. When RRs were not available in the published article, they were computed from the exposure distributions. Two investigators extracted the data independently and discrepancies were resolved by discussion with a third investigator. We performed random-effect meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 20-g/d increment of fish consumption. RESULTS: Forty-two studies, comprising 27 independent cohorts, met our inclusion criteria. The studies included 2325040 participants and 24115 incident cases of gastrointestinal cancer, with an average follow-up of 13.6 years. Compared with individuals who did not eat, or seldom ate, fish, the pooled RR of gastrointestinal cancers was 0.93 (95%CI: 0.88-0.98) for regular fish consumers, 0.94 (0.89-0.99) for low to moderate fish consumers, and 0.91 (0.84-0.97) for high fish consumers. Overall, a 20-g increase in fish consumption per day was associated with a 2% reduced risk of gastrointestinal cancers (RR = 0.98; 95%CI: 0.96-1.01). In subgroup analyses, we noted that fish consumption was associated with reduced risk of colorectal (RR = 0.93; 95%CI: 0.87-0.99; P < 0.01), esophageal (RR = 0.91; 95%CI: 0.83-0.99; P < 0.05) and hepatocellular cancers (RR = 0.71; 95%CI: 0.48-0.95; P < 0.01). CONCLUSION: This meta-analysis suggested that fish consumption may reduce total gastrointestinal cancer incidence. Inverse relationships were also detected between fish consumption and specific types of cancers.


Assuntos
Dieta , Peixes , Neoplasias Gastrointestinais/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Alimentos Marinhos , Animais , Estudos de Coortes , Dieta/efeitos adversos , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Razão de Chances , Fatores de Proteção , Medição de Risco , Fatores de Risco
11.
Asian Pac J Cancer Prev ; 15(18): 7919-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25292087

RESUMO

20(S)-Protopanaxadiol (PPD), a ginsenoside isolated from Pananx quinquefolium L., has been shown to inhibit growth and proliferation in several cancer cell lines. The aim of this study was to evaluate its anticancer activity in human breast cancer cells. MCF-7 cells were incubated with different concentrations of 20(S)-PPD and cytotoxicity was evaluated by MTT assay. Occurrence of apoptosis was detected by DAPI and Annexin V-FITC/PI double staining. Mitochondrial membrane potential was measured with Rhodamine 123. The Bcl-2 and Bax expression were determined by Western blot analysis. Caspase activity was measured by colorimetric assay. 20(S)-PPD dose-dependently inhibited cell proliferation in MCF-7 cells, with an IC50 value of 33.3 µM at 24h. MCF-7 cells treated with 20(S)-PPD presented typical apoptosis, as observed by morphological analysis in cell stained with DAPI. The percentages of annexin V-FITC positive cells were 8.92%, 17.8%, 24.5% and 30.5% in MCF-7 cells treated with 0, 15, 30 and 60µM of 20(S)-PPD, respectively. Moreover, 20(S)-PPD could induce mitochondrial membrane potential loss, up-regulate Bax expression and down-regulate Bcl-2 expression. These events paralleled activation of caspase-9, -3 and PARP cleavage. Apoptosis induced by 20(S)-PPD was blocked by z-VAD-fmk, a pan-caspase inhibitor, suggesting induction of caspase-mediated apoptotic cell death. In conclusion, the 20(S)-PPD investigated is able to inhibit cell proliferation and to induce cancer cell death by a caspase-mediated apoptosis pathway.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Caspases/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Sapogeninas/farmacologia , Antidepressivos/farmacologia , Western Blotting , Neoplasias da Mama/enzimologia , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Feminino , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Transdução de Sinais , Células Tumorais Cultivadas
12.
J Dig Dis ; 15(1): 5-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24118892

RESUMO

OBJECTIVE: We aimed to describe the clinical picture, management and outcomes of Chinese patients with peptic ulcer bleeding (PUB), especially in those with high risks. METHODS: A multicenter endoscopic survey was conducted. All consecutive patients with endoscopy confirmed PUB from October 2010 to June 2011 were enrolled. Data including patients' gender, age, symptoms and endoscopic findings, Forrest classification, and endoscopic and medical treatment were documented. High-risk ulcer was defined as Forrest grades Ia to IIb upon endoscopy. Rates of rebleeding, surgery and mortality were recorded. RESULTS: In all, 1006 patients were included. Of these 437 (43.4%) were categorized with high-risk PUB, among whom 110 (25.2%) received endoscopic treatment, and the success rate was 99.1%. Rebleeding rates 1-3 days, 4-5 days and 6-30 days after treatment in high-risk patients who did and did not receive endoscopic treatment were 10.9% versus 10.4%, 3.6% versus 3.7% and 0.9% versus 1.5%, respectively. The surgery rates of high-risk patients with or without endoscopic treatment were 1.8% (2/110) versus 1.8% (6/327). During the 9-month study period, two patients with high-risk PUB died, therefore, the overall mortality rate of high-risk PUB was 0.5% (2/437). CONCLUSION: The study suggests that the proportions of high-risk PUB in China is 43.4%, while rebleeding and surgery rate after endoscopic treatment as well as the mortality rate of high-risk PUB in China are 15.6%, 1.8% and 0.5%, respectively.


Assuntos
Endoscopia Gastrointestinal , Úlcera Péptica Hemorrágica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/mortalidade , Estudos Prospectivos
13.
Am J Chin Med ; 41(5): 1137-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24117074

RESUMO

20(S)-Protopanaxadiol (PPD), an aglycone saponin ginsenoside isolated from Panax quinquefolium L, has been shown to inhibit the growth and proliferation in several cancer lines. However, the underlying molecular mechanisms remain poorly understood. In this study, we investigated the apoptosis-induced effects and the mechanism of 20(S)-PPD on human lung adenocarcinoma A549 cells. 20(S)-PPD showed a potent antiproliferative activity against A549 cells by triggering apoptosis. 20(S)-PPD-induced apoptosis was characterized by a dose-dependent loss of the mitochondrial membrane, release of cytochrome c, second mitochondria-derived activator of caspase (Smac) and apoptosis-inducing factor (AIF), activation of caspase-9/-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Caspase-dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate 20(S)-PPD-induced apoptosis. After treatment with 20(S)-PPD, the proportion of A549 cells at the G0/G1 phase increased, while cells at the S and G2/M phases decreased. Furthermore, 20(S)-PPD also triggered down-regulation of phosphorylated Akt (Ser473/Thr308) and glycogen synthase kinase 3ß (GSK 3ß). Knockdown of GSK 3ß with siRNA promoted the apoptotic effects of 20(S)-PPD. These results revealed an unexpected mechanism of action for this unique ginsenoside: triggering a mitochondrial-mediated, caspase-dependent apoptosis via down-regulation of the PI3K/Akt signaling pathway in A549 cells. Our findings encourage further studies of 20(S)-PPD as a promising chemopreventive agent against lung cancer.


Assuntos
Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína Oncogênica v-akt/fisiologia , Panax , Fosfatidilinositol 3-Quinases/fisiologia , Sapogeninas/farmacologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Adenocarcinoma/prevenção & controle , Caspases/metabolismo , Caspases/fisiologia , Relação Dose-Resposta a Droga , Humanos , Neoplasias Pulmonares/prevenção & controle , Potencial da Membrana Mitocondrial/genética , Potencial da Membrana Mitocondrial/fisiologia , Fitoterapia , Sapogeninas/uso terapêutico , Células Tumorais Cultivadas
14.
Oncol Res ; 20(8): 359-68, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23924856

RESUMO

Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diterpenos/farmacologia , Neovascularização Patológica/prevenção & controle , Neoplasias Pancreáticas/tratamento farmacológico , Fenantrenos/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Regulação para Baixo , Compostos de Epóxi/farmacologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Pancreáticas/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
World J Gastroenterol ; 19(24): 3770-80, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23840115

RESUMO

AIM: To investigate the biological function of 14-3-3σ protein and to look for proteins that interact with 14-3-3σ protein in colon cancer stem cells. METHODS: Reverse transcription polymerase chain reaction was performed to amplify the 14-3-3σ gene from the mRNA of colon cancer stem cells. The gene was then cloned into the pGEM-T vector. After being sequenced, the target gene 14-3-3σ was cut from the pGEM-T vector and cloned into the pGBKT7 yeast expression plasmid. Then, the bait plasmid pGBKT7-14-3-3σ was transformed into the yeast strain AH109. After the expression of the pGBKT7-14-3-3σ fusion protein in the AH109 yeast strain was accomplished, a yeast two-hybrid screening assay was performed by mating AH109 with Y187 that contained a HeLa cDNA library plasmid. The interaction between the 14-3-3σ protein and the proteins obtained from positive colonies was further confirmed by repeating the yeast two-hybrid screen. After extracting and sequencing the plasmids from the positive colonies, we performed a bioinformatics analysis. A coimmunoprecipitation assay was performed to confirm the interaction between 14-3-3σ and the proteins obtained from the positive colonies. Finally, we constructed 14-3-3σ and potassium channel modulatory factor 1 (KCMF1) siRNA expression plasmids and transfected them into colon cancer stem cells. RESULTS: The bait plasmid pGBKT7-14-3-3σ was constructed successfully, and the 14-3-3σ protein had no toxic or autonomous activation effect on the yeast. Nineteen true-positive colonies were selected and sequenced, and their full-length sequences were obtained. We searched for homologous DNA sequences for these sequences from GenBank. Among the positive colonies, four coding genes with known functions were obtained, including KCMF1, quinone oxidoreductase (NQO2), hydroxyisobutyrate dehydrogenase (HIBADH) and 14-3-3σ. For the subsequent coimmunoprecipitation assay, the plasmids PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH were successfully constructed, and the sequences were further confirmed by DNA sequencing. The Fugene 6 reagent was used to transfect the plasmids, and fluorescence-activated cell sorting analysis showed the transfection efficiency was 97.8% after 48 h. The HEK 293FT cells showed the stable expression of the PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH plasmids. After anti-Myc antibody immunoprecipitation with Myc-KCMF1, Myc-NQO2 and Myc-HIBADH from cell lysates, the presence of Flag-14-3-3σ protein in the immunoprecipitated complex was determined by western blot analysis. The knock-down expression of the 14-3-3σ and KCMF1 proteins significantly inhibited cell proliferation and colony formation of SW1116csc. CONCLUSION: Genes of the proteins that interacted with 14-3-3σ were successfully screened from a HeLa cDNA library. KCMF1 and 14-3-3σ protein may affect the proliferation and colony formation of human colon cancer stem cells.


Assuntos
Proteínas 14-3-3/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias do Colo/patologia , Exonucleases/metabolismo , Células-Tronco Neoplásicas/patologia , Mapas de Interação de Proteínas/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Células Cultivadas , Neoplasias do Colo/metabolismo , DNA Complementar/genética , Exonucleases/genética , Exorribonucleases , Fusão Gênica/genética , Técnicas de Silenciamento de Genes , Vetores Genéticos/genética , Células HeLa , Humanos , Imunoprecipitação , Células-Tronco Neoplásicas/metabolismo , Plasmídeos/genética , Mapas de Interação de Proteínas/genética , Ubiquitina-Proteína Ligases/genética
16.
World J Gastroenterol ; 19(20): 3130-3, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23716994

RESUMO

AIM: To detect the expression of huCdc7 in colorectal cancer. METHODS: The mRNA and protein expression of huCdc7 in 39 colorectal cancer tissue specimens and matched tumor-adjacent normal colorectal tissue specimens was detected by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: The relative expression level of huCdc7 mRNA in colorectal cancer was significantly higher than that in tumor-adjacent normal colorectal tissues (0.03675 ± 1.00 vs 0.01199 ± 0.44, P < 0.05). huCdc7-positive cells displayed brown granules in the nucleus. Tumor tissues contained many huCdc7-positive cells, whereas normal colorectal tissues contained very few positive cells. CONCLUSION: huCdc7 may play an important role in the development and progression of colorectal cancer.


Assuntos
Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/análise , Neoplasias Colorretais/química , Proteínas Serina-Treonina Quinases/análise , Biomarcadores Tumorais/genética , Biópsia , Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Imuno-Histoquímica , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
17.
Dalton Trans ; 42(11): 3860-8, 2013 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-23318810

RESUMO

Two series of ligand precursors [2-OH-3-(CH(2)NR(2))-5-MeC(6)H(2)](2)CH(2) (1: NR(2) = NMe(2); 2: NR(2) = N(CH(2))(4); 3: NR(2) = N(CH(2))(5); 4: NR(2) = N(Me)Ph) and [2-OH-3-(CH=NR)-5-MeC(6)H(2)](2)CH(2) (10: R = 2,6-Pr(2)(i)C(6)H(3); 11: R = p-MeC(6)H(4); 12: R = p-ClC(6)H(4); 13: R = p-MeOC(6)H(4); 14: R = Bu(t)) were prepared. These compounds reacted with AlMe(3) to afford corresponding dinuclear aluminum complexes [AlMe(2){2-O-3-(CH(2)NR(2))-5-MeC(6)H(2)}](2)CH(2) (6: NR(2) = NMe(2); 7: NR(2) = N(CH(2))(4); 8: NR(2) = N(CH(2))(5); 9: NR(2) = N(Me)Ph) and [AlMe(2){2-O-3-(CH=NR)-5-MeC(6)H(2)}](2)CH(2) (15: R = 2,6-Pr(2)(i)C(6)H(3); 16: R = p-MeC(6)H(4); 17: R = p-ClC(6)H(4); 18: R = p-MeOC(6)H(4); 19: R = Bu(t)). All the compounds were characterized by (1)H and (13)C NMR spectroscopy and elemental analyses. Complexes 6 and 16 were additionally characterized by single crystal X-ray diffraction techniques. Catalysis of the aluminum complexes towards the ring-opening polymerization of rac-lactide was evaluated in the presence of benzyl alcohol. All the polymerization reactions proceed in a controlled manner.


Assuntos
Compostos de Alumínio/química , Complexos de Coordenação/química , Dioxanos/química , Fenóis/química , Compostos de Alumínio/síntese química , Catálise , Complexos de Coordenação/síntese química , Dioxanos/síntese química , Cinética , Espectroscopia de Ressonância Magnética , Fenóis/síntese química , Polimerização
18.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 6): o1598, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22719406

RESUMO

In the crystal structure of the title compound, C(9)H(6)Cl(3)NO(3), mol-ecules are connected by C-H⋯O hydrogen bonds, forming chains along the b axis. The dihedral angle between the benzene ring and the plane of the nitro group is 16.2 (1)° and that between the benzene ring and the plane of the dichloro-allyl group is 10.2 (1)°.

19.
Food Chem Toxicol ; 50(3-4): 590-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22266044

RESUMO

Juglone, a major chemical constituent of Juglans mandshruica Maxim, is a promising anticancer agent that has shown a strong activity against cancer cells in vitro. Our previous study showed that juglone inhibited the proliferation of HL-60 cells with an IC50 value ∼8 µM. To further explore the proapoptotic mechanism of juglone, we investigated the role of the reactive oxygen species (ROS) in the apoptosis induced by juglone in HL-60 cells. The generation of ROS was about 2 to 8-fold as compared to control cell after treatment with juglone (2, 4 and 8 µM) for 24 h. The glutathione (GSH) depletion was consistent with ROS generation after treatment with juglone. Reversal of apoptosis in antioxidants (NAC and catalase) pretreated cells indicated the involvement of ROS in juglone-induced apoptosis. The cleavage of PARP and procaspase-3 and -9, loss of mitochondrial membrane potential (△Ψm), and release of cytochrome c (Cyt c) and Smac induced by juglone were significantly blocked by NAC. NAC also prevented the inhibition the phosphorylation of Akt and mTOR proteins by juglone. Collectively, these results indicated that ROS played a significant role in the apoptosis induced by juglone in human leukemia cell HL-60.


Assuntos
Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Juglans/química , Leucemia/patologia , Naftoquinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Anexina A5/metabolismo , Antioxidantes/farmacologia , Caspases/metabolismo , Citocromos c/metabolismo , Ativação Enzimática , Glutationa/metabolismo , Células HL-60 , Humanos , Potenciais da Membrana/efeitos dos fármacos
20.
Zhonghua Yi Xue Za Zhi ; 92(42): 2965-7, 2012 Nov 13.
Artigo em Chinês | MEDLINE | ID: mdl-23328285

RESUMO

OBJECTIVE: To analyze the clinical features, risk factors and drug uses of senior hospitalized patients with chronic constipation. METHODS: A total of 162 hospitalized patients aged 85 years and over at our hospital during the period of January-March 2012 conducted a questionnaire survey. There were 137 males and 25 females. And 112 cases of chronic constipation were diagnosed in accordance with the Rome III criteria. The survey included general condition, risk factors of constipation, spectrum of symptoms, associated symptoms, previous medication and medication for constipation after admission. The results were statistically analyzed by Logistic regression. RESULTS: Their average age was (90 ± 4) years old. And the total prevalence of chronic constipation was 69.1% (112/162). Logistic regression analysis showed that less activity (OR = 10.873) and diet (OR = 4.752) were the important risk factors. Defecation effort was the most common symptom (n = 85, 75.9%). A total of 88 cases (78.6%) took lactulose alone or lactulose plus other laxatives. The reasons of using lactulose were as follows: dietary restrictions (n = 31, 35.2%), aspiration prevention (n = 21, 23.9%) and poor efficacy of other laxatives (n = 36, 40.9%). CONCLUSIONS: Prevalence of constipation is high among senior hospitalized patients. Less activity and diet are the main risk factors. And lactulose should be a first-line therapy.


Assuntos
Constipação Intestinal/diagnóstico , Inquéritos e Questionários , Idoso de 80 Anos ou mais , Dieta , Feminino , Humanos , Pacientes Internados , Lactulose/uso terapêutico , Modelos Logísticos , Masculino , Atividade Motora , Fatores de Risco
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