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OBJECTIVE: To investigate the potential association between Dietary Inflammatory Index (DII) scores and constipation among a sample of adults in the United States. METHODS: This cross-sectional study used data from adult participants in the 2005 to 2010 National Health and Nutrition Examination Survey (ie, "NHANES"). Self-reported information was used to identify cases of constipation. The DII was used to assess inflammatory potential of the diet. Odds ratios (ORs) and corresponding 95% CIs for the association between the DII and constipation were determined using multivariate logistic regression modeling. Stratified analyses explored whether there was effect modification to influence the relationship between DII and constipation. RESULTS: Of 8272 subjects, 759 reported constipation, and 7513 did not, corresponding to a prevalence of 9.2%. After adjusting for age, gender, race/ethnicity, marital status, education level, smoking status, alcohol consumption, physical activity, body mass index (BMI), cardiovascular diseases (CVD), hypertension, stroke, diabetes, energy intake, carbohydrate intake, and selective serotonin reuptake inhibitor (SSRI) use. Compared with lower DII scores group T1 (-5.28 to ≤0.72), the adjusted OR values for DII scores and constipation in T2 (>0.72 to ≤2.50) and T3 (>2.50 to 5.24) were 1.27 (95% CI: 1.02-1.58, P=0.029) and 1.43(95% CI: 1.14-1.8, P=0.002). Subgroup analyses showed that there were effect modification of gender and physical activity factors on DII scores and constipation. CONCLUSIONS: Results of this cross-sectional study suggest that a higher dietary inflammatory index score was associated with increased risk of constipation after adjustment for confounding in a multivariable analysis. gender and physical activity were found to be an effect modifier of this relationship.
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Scutellaria barbata D. Don, a traditional Chinese medicine, reportedly possesses antitumor activity against a variety of tumors. In the present study, we investigated the cytotoxic effect of total flavonoids from S. barbata (TF-SB) on human hepatocarcinoma cells and the underlying molecular mechanisms regarding the effect were explored. TF-SB treatment significantly reduced the cell viability of human HCC MHCC97-H cells in a dose-dependent manner. Further flow cytometric analysis showed that the apoptosis rate of MHCC97-H cells increased and the mitochondrial membrane potential (∆ψm) of MHCC97-H cells decreased after TF-SB treatment. DNA ladder showed that TF-SB induced a significant increase in DNA fragmentation in MHCC97-H cells. Reverse transcription PCR and Western blot analysis revealed that the expression levels of Smac, Apaf-1, Cytochrome c, Caspase-9, and Caspase-3 were upregulated in a dose-dependent manner and after treatment with different concentrations of TF-SB for 48 h. These results suggest that TF-SB induces apoptosis in MHCC97-H cells through the mitochondrial pathway.
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Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Flavonoides/farmacologia , Neoplasias Hepáticas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Apoptose , Western Blotting , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , ScutellariaRESUMO
BACKGROUND: ß-elemene, a natural sesquiterpene extracted from the essential oils of Curcuma aromatica Salisb, has been shown to be effective against a wide range of tumors. In this study, the antitumor effect of ß-elemene on a human hepatoma cell line, HepG2, and the mechanism involved have been investigated. METHODS: MTT assay was used to determine the growth inhibition of hepatoma HepG2 cells in vitro. Apoptosis of HepG2 cells were demonstrated by fluorescence microscope with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Flow cytometry was performed to analyze the cell cycle distribution of HepG2 cells. The mRNA and protein expression of Fas and FasL were measured by RT-PCR and Western blot analysis. RESULTS: MTT results showed that ß-elemene could inhibit the proliferation of HepG2 cells in a time- and dose- dependent manner. Our results showed ß-elemene had positive effect on apoptosis through fluorescence microscope and flow cytometry assay. Furthermore, ß-elemene could induce the cell cycle arrest of the HepG2 cells in the G2/M phase. Fas and FasL expression were obviously increased after ß-elemene treatment in both mRNA and protein level. CONCLUSION: The present study indicates that ß-elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells, and the apoptosis induction is related with up-regulating of Fas/FasL expression.
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BACKGROUND: Angiogenesis is closely related to the growth, invasion and metastasis of tumors, also considered as the key target of anticancer therapy. Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is being used to treat various diseases, including cancer. However, the antitumor molecular mechanism of S. barbata was still unclear. This study aimed to investigate the inhibitory effects of the total flavones in S. barbata (TF-SB) on angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with various concentrations of TF-SB. Cell viability was examined using the MTT assay. The scratch assay was used to detect the migration of HUVECs after treatment with TF-SB. The ability of HUVECs to form network structures in vitro was demonstrated using the tube formation assay. The chick embryo chorioallantoic membrane assay was performed to detect the in vivo anti-angiogenic effect. The expression of VEGF was measured by the enzyme-linked immunosorbent. RESULTS: Results showed that TF-SB inhibited the proliferation and migration of HUVECs in a dose- dependent manner. Simultaneously, TF-SB significantly suppressed HUVEC angiogenesis in vitro and in vivo. Furthermore, VEGF was downregulated in both HUVECs and MHCC97-H cells after TF-SB treatment. CONCLUSION: TF-SB could suppress the process of angiogenesis in vitro and in vivo. TF-SB potentially suppresses angiogenesis in HUVECs by regulating VEGF. These findings suggested that TF-SB may serve as a potent anti-angiogenic agent.
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Inibidores da Angiogênese/farmacologia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Scutellaria/química , Animais , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Metastasis is the major cause of cancer-related deaths. Targeting the process of metastasis has been proposed as a strategy to fight cancer. Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used for treatment of many diseases, including cancer. This study aimed to determine the anti-metastatic effect of total flavonoids of S. barbata (TF-SB) using the human hepatocarcinoma MHCC97H cell line with high metastatic potential. Our results show that TF-SB could significantly inhibit the proliferation and invasion of MHCC97H cells in a dose-dependent manner. MMP-2 and MMP-9 expression were obviously decreased after TF-SB treatment at both the mRNA and protein level. TIMP-1 and TIMP-2 expression were simultaneously increased. The present study indicates that TF-SB could reduce the metastatic capability of MHCC97H cell, probably through decrease of the MMP expression, and simultaneous increase of the TIMP expression.
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Antineoplásicos Fitogênicos/farmacologia , Movimento Celular/efeitos dos fármacos , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Scutellaria/química , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
BACKGROUND: Cyclooxygenase-2(COX-2) promotes carcinogenesis, tumor proliferation, angiogenesis, prevention of apoptosis, and immunosuppression. Meanwhile, COX-2 over-expression has been associated with tumor behavior and prognosis in several cancers. This study investigated the antitumor effects of the selective COX-2 inhibitor, Celecoxib, on breast cancer in vitro and in vivo. METHODS: Human breast cancer MCF-7 and MDA-MB-231 cells were cultured with different concentration (10, 20, 40 µmol/L) of celecoxib after 0-96 hours in vitro. MTT assay was used to determine the growth inhibition of breast cancer cells in vitro. The expression of COX-2 on mRNA was measured by real-time quantitive PCR analysis. Flow cytometry was performed to analyze the cell cycle of MCF-7 cells. Levels of PGE2 were measured by ELISA method. The in vivo therapeutic effects of celecoxib were determined using rat breast cancer chemically induced by 7,12-dimethylben anthracene (DMBA). RESULTS: The inhibition of proliferation of both MCF-7 and MDA-MB-231 cells in vitro by celecoxib was observerd in time and dose dependent manner. Celecoxib effectively down-regulated the expression of COX-2. The cell cycle was arrested at G0/G1, and rate of cells in S phase was obviously decreased. Levels of PGE2 were inhibited by Celecoxib. The tumor incidence rate of the celecoxib group was lower than that of the control group. In addition, the tumor latency period of the celecoxib group was longer than that of the control group. CONCLUSIONS: Celecoxib inhibited the proliferation of breast cancer cell lines in vitro, and prevented the occurrence of rat breast cancer chemically induced by DMBA. Therefore, celecoxib exhibits an antitumor activity and seems to be effective in anti-tumor therapy.
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Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Sirolimo/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Cadaverina/análogos & derivados , Cadaverina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Células NIH 3T3 , Neoplasias Pancreáticas/ultraestrutura , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Vacúolos/ultraestrutura , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Cancer is a major cause of morbidity and mortality. Chemotherapy is one of the main means of cancer treatment. Conventional chemotherapy agents kill rapidly proliferating cells, resulting in some of the most common side effects of chemotherapy. Liposome-encapsulated drugs offer the possibility to increase target efficacy as well as reducing toxic side effects of chemotherapeutic drugs. However, the target specificity of liposome is dissatisfied. We urgently need to develop new approaches to improving drug target efficacy. Recently, sonodynamic therapy (SDT) of cancer, which is based on preferential uptake and retention of a sonosensitizer in tumor tissues and subsequent activation of drug by ultrasound radiation, is a developing field. In this article, we propose the use of sonosensitizers in combination with liposome to target chemotherapy drugs directly to tumor cells. SDT with low-intensity ultrasound combined with a sonosensitizer may be a promising approach to cancer therapy.
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Antineoplásicos/uso terapêutico , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Terapia por Ultrassom , Antineoplásicos/administração & dosagem , Humanos , Lipossomos , Modelos TeóricosRESUMO
Esophageal duplication cysts are benign, asymptomatic anomalies of foregut formation. We report a case of esophageal duplication cyst with esophageal squamous cancer. An upper endoscopy visualized with esophageal scan disclosed a stenotic lesion in the lower esophagus. Computed tomography images revealed a cystic mass in the inferior mediastinum, which was on the right wall of the esophagus. The postoperative pathology report confirmed the diagnosis of esophageal squamous cancer (ulcer type) and esophageal duplication cyst with calcification.
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Carcinoma de Células Escamosas/complicações , Cisto Esofágico/congênito , Neoplasias Esofágicas/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Cisto Esofágico/complicações , Cisto Esofágico/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene, its inactivation due to hypermethylation related to carcinogenesis. The aim of this study was to investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-CdR) on cell proliferation and apoptosis by demethylation of the promoter region and restoring the expression of RUNX3 in the breast cancer MCF-7 cell line. MCF-7 cells were cultured with different concentrations (0.4-102.4 µmol/L) of 5-Aza-CdR in vitro. MTT assay was used to determine the proliferation of MCF-7 cells. Flow cytometry and Hoechst staining were used for analyzing cell apoptosis. The methylation status and expression of RUNX3 in mRNA and protein levels were measured by methylation-specific polymerase chain reaction (PCR [MSP]), reverse transcription (RT)-PCR, and Western blot. It was shown that the RUNX3 gene downregulated and hypermethylated in MCF-7 cells. 5-Aza-CdR induced demethylation, upregulated the expression of RUNX3 on both mRNA and protein levels in cancer cells, and induced growth suppression and apoptosis in vitro in a dose- and time-dependent manner. The results demonstrate that RUNX3 downregulation in breast cancer is frequently due to hypermethylation, and that 5-Aza-CdR can inhibit cell proliferation and induce apoptosis by eliminating the methylation status of RUNX3 promoter and restoring its expression.
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The mammalian target of rapamycin (mTOR) is a protein kinase that regulates protein translation, cell growth, and apoptosis. Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Recent studies showing that RPM sensitizes cancers to chemotherapy and radiation therapy have attracted considerable attention. This study aimed to examine the radiosensitizing effect of RPM in vitro, as well as its mechanism of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay showed that 10 nmol/L to 15 nmol/L of RPM had a radiosensitizing effects on pancreatic carcinoma cells in vitro. Furthermore, a low dose of RPM induced autophagy and reduced the number of S-phase cells. When radiation treatment was combined with RPM, the PC-2 cell cycle arrested in the G2/M phase of the cell cycle. Complementary DNA (cDNA) microarray and reverse transcription polymerase chain reaction (RT-PCR) revealed that the expression of DDB1, RAD51, and XRCC5 were downregulated, whereas the expression of PCNA and ABCC4 were upregulated in PC-2 cells. The results demonstrated that RPM effectively enhanced the radiosensitivity of pancreatic carcinoma cells.
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Neoplasias Pancreáticas/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used to treat cancers, inflammation, and urinary diseases. This study aimed to determine any protective effects of S. barbata crude extract (CE-SB) against rat liver tumorigenesis induced by diethylnitrosamine (DENA). Liver malfunction indices in serum were measured by biochemical examination. Hematoxylin and eosin staining was performed to examine liver pathology. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in liver homogenates to evaluate oxidative stress. The levels of liver malfunction indices in the CE-SB groups, especially in the CE-SB high dose group, were lower than that of the model group (P<0.05). The results from histological examination indicated that the number of liver nodules in the CE-SB groups decreased compared with the model group (P<0.05). Content of MDA determined in liver was significantly decreased, and level of SOD elevated by CE-SB. CE-SB can inhibit experimental liver tumorigenesis and relieve hepatic injury in rats.