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ABSTRACT: PURPOSE: Observational studies on the association between white meat (including fish and poultry) intake and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer, have reported mixed results. To provide a quantitative assessment of this association, we summarized the evidence from observational studies. METHODS: Relevant studies published on or before April 30, 2012 were identified from MEDLINE and EMBASE. Summary effect size estimates with 95% confidence intervals (CIs) were calculated with a random-effects model. Between-study heterogeneity was assessed using the Cochran Q and I(2) statistics. RESULTS: A total of 23 publications from 21 independent studies (16 case-control and 5 cohort studies) were included in this meta-analysis. Based on high versus low analysis, the summary effect size estimate of CRA was 0.96 (95% CI, 0.84-1.09) for white meat intake, 0.98 (95% CI, 0.80-1.19) for fish intake, and 0.98 (95% CI, 0.80-1.18) for poultry intake. Subgroup analyses revealed that the null associations of CRA with intake of white meat (fish/poultry) were independent of geographic locations, study design, type of food frequency questionnaire, number of cases, and adjustments for confounders, such as body mass index, use of nonsteroidal anti-inflammatory drugs, dietary energy intake, smoking, and physical activity. CONCLUSIONS: Intake of white meat (fish/poultry) is not associated with the risk of CRA.
Annals of epidemiology 01/2013; · 2.95 Impact Factor
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ABSTRACT: Protein inhibitor of activated STAT-1 (PIAS1) is a novel modulator of the JAK/STAT signaling pathway that negatively regulates the inflammatory response. It has been also reported to be downregulated in a variety of human cancer cell lines. However, the role of PIAS1 in gastric cancer remains unclear. In this study, we investigated the prognostic value of PIAS1 expression and its regulated mechanisms in gastric cancer cell metastasis. Therefore, the expression of PIASI was explored in gastric cancer tissues and adjacent tissues of gastric cancer with 31 cases of patients, and the prognostic value was analyzed. In addition, the growth and invasion in SGC7901 cells were investigated in the restoration of PIAS1 expression with Ad5/F35-PIAS1 or Ad5/F35-vector or PBS treatment, and the activity of P38MAPK, P-P38MAPK, JNK/SAPK, P-JNK/SAPK, ERK and P-ERK, were detected by western blotting. The tumor migratory factors MMP-9, MMP-2 and ICAM-1 were analyzed by western blotting. The results demonstrated that 22 of 31 (70.9%) gastric cancer specimens showed low levels of PIAS1 expression from immunohistochemistry staining using tissue microarrays. Statistical analysis suggested that the downregulation of PIAS1 was significantly correlated with tumor staging. Furthermore, we found that the restoration of PIAS1 expression mediated by Ad5/F35 virus suppressed cell proliferation and invasion accompanied by the inhibition of P38MAPK and ERK protein expression and activity, but not JNK/SAPK protein. Notably, PIAS1 restoration with the transfection of Ad5/F35-PIAS1 robustly decreased the expression of tumor migratory factors including MMP-9, MMP-2 and ICAM-1 compared to Ad5/F35-vector. These data suggest that PIAS1 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting the MAPK signaling pathway.
Oncology Reports 09/2012; 28(6):2149-55. · 1.84 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is receiving increased attention. This study was designed to investigate the effect of selective Cyclooxygenase-2 (COX-2) inhibitor, nimesulide, on the expression of Smad4 in human hepatocellular carcinoma HepG2.
HepG2 cells were incubated in various concentrations of nimesulide (25, 50, 100, 200, 400 μmol/L) to detect the effect of proliferation by MTS. The apoptosis of HepG2 was determined by TUNEL; fluorescence microscope was used to observe the expression of Smad4.
The result showed that nimesulide inhibited the proliferation of HepG2 cell in a concentrations-dependent manner, and promoted the karyopyknosis and fragmentation of HepG2 cell nucleus, induced its apoptosis, the number of fluorescence labeling of Smad4 in Nimesulide group was higher than control group (P<0.05).
Nimesulide inhibits the proliferation and promotes apoptosis of HepG2 by up-regulation of Smad4 in HepG2.
Indian Journal of Pharmacology 09/2012; 44(5):599-601. · 0.27 Impact Factor
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ABSTRACT: Severe acute pancreatitis (SAP) can lead to multiple-organ dysfunction syndrome (MODS). Electrocardiographic (ECG), cardiac enzyme, and serum magnesium abnormalities occur after SAP. Electrocardiographic and cardiac enzyme abnormalities are described as variables in SAP patients, which contribute to the effects of MODS. Hypomagnesium is also closely associated with ECG abnormalities; therefore, hypomagnesium was also considered to be a variable in this study. A consecutive series of 54 patients admitted within 72 hours after SAP occurred was studied. A standard 12-lead ECG, cardiac enzyme, and serum magnesium measurement were routinely performed at admission. Linear correlation was used to analyze the relationship between hypomagnesemia and sinus tachycardia. The nonparametic binomial test was used to analyze dichotomized dependent variables (premature beat, atrial fibrillation, ST-segment depression, abnormal T wave, and long QT interval). Hypomagnesemia was present in 15 patients (28%), who subsequently had sinus tachycardia. There was a significant negative relationship (-1 < r <0) between hypomagnesemia and sinus tachycardia (p < .05). There were 14 (17%) premature beat, 7 (8%) atrial fibrillation, 21 (25%) ST-segment depression, 18 (21%) abnormal T wave, and 17 (31%) long QT-interval events in 54 SAP patients. Hypomagnesemia is a reason for ECG abnormalities. Electrocardiographic and cardiac enzyme abnormalities are considered to be transitory variables that are present in patients with SAP.
Gastroenterology nursing: the official journal of the Society of Gastroenterology Nurses and Associates 07/2012; 35(4):256-60. · 0.47 Impact Factor
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ABSTRACT: Fractalkine (FKN), a chemokine that acts as both an adhesion molecule and a chemoattractant, is expressed in many inflammatory diseases. Chemokines play a crucial role in severe acute pancreatitis (SAP). This study used adenovirus-mediated siRNA to target FKN overexpression and assessed its ability to suppress inflammation development in a SAP rat model. Adenovirus-mediated FKN siRNA was transfected into cerulein-stimulated AR42J cells. The growth of cerulein-stimulated AR42J cells was determined by colony formation and MTT assays. The inhibitory effect of the FKN siRNA was studied in a SAP rat model in vivo and detected by ELISA, RT-PCR, western blot analysis and immunohistochemistry. FKN, IL-8 and TNF-α were found to be overexpressed in cerulein-stimulated AR42J cells by ELISA and western blot analysis (P<0.05). The animal experiments confirmed that FKN siRNA could inhibit inflammation development in SAP. The values of serum FKN, TNF-α and IL-8 levels were decreased after FKN siRNA treatment (P<0.05). Furthermore, western blotting and RT-PCR analysis showed that FKN protein and mRNA levels were decreased after injection with FKN siRNA (P<0.05). Immunohistochemistry also showed that inflammation was decreased after injection with FKN-siRNA in the SAP rat model. Treatment with siRNA can inhibit FKN overexpression and also suppresses inflammation development in a SAP rat model. More importantly, this study indicated that FKN, which is overexpressed in the SAP rat model, may serve as a novel and effective therapeutic target for SAP.
International Journal of Molecular Medicine 06/2012; 30(3):514-20. · 1.98 Impact Factor
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ABSTRACT: To investigate the effect of metformin on the expression profiles of microRNAs in human pancreatic cancer cells.
MicroRNAs real-time PCR Array was applied to investigate differentially expressed miRNAs in Sw1990 cells treated with or without metformin. Stem-loop real time RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-26a on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, Apoptosis assay, Matrigel invasion and migration assay. HMGA1 was proved to be a target of miR-26a by Luciferase reporter assay, Real-time PCR and Western-blotting.
Nine miRNAs were significantly up-regulated in metformin treated cells. Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner. Forced expression of miR-26a significantly inhibited cell proliferation, invasion, migration and increased cell apoptosis, whereas knockdown of miR-26a obtained the opposite effect. Furthermore, we demonstrated that HMGA1, an oncogene, is a direct target of miR-26a. Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo.
These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of metformin.
Diabetes research and clinical practice 01/2012; 96(2):187-95. · 2.16 Impact Factor
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ABSTRACT: Interferon-alpha (IFN-alpha) treatment is associated with up-regulation of epidermal growth factor receptor (EGFR) expression and marked growth inhibition of colon cancer cell lines. We aimed to determine the effect of combining IFN-alpha and gefitinib in the growth of human colon cancer cell lines.
Two human colon cancer cell lines SW480 and LOVO were treated with IFN-alpha alone or gefitinib alone or IFN-alpha plus gefitinib. Proliferation of colon cancer cells was measured by methyl thiazolyl tetrazolium (MTT) assay; the apoptosis rate was analysed by flow cytometry (FCM). The expression of XIAP, XAF1 mRNA was detected by RT-PCR and the expression of XlAP XAF1 protein was detected by western blotting.
Methyl thiazolyl tetrazolium showed that IFN-alpha, gefitinib and IFN-alpha plus gefitinib significantly inhibited SW480 and LOVO cells in a dose-dependent manner (p < 0.05). The FCM revealed that lFN-alpha, gefitinib and IFN-alpha plus gefitinib could markedly upgrade the apoptosis rate (p < 0.05). The expression of XIAP mRNA down-regulated markedly (p < 0.05) while the expression of XAF1 mRNA up-regulated significantly (p < 0.05). The expression of XIAP protein was down-regulated markedly (p < 0.05) while the expression ofXAF1 protein was up-regulated significantly (p < 0.05).
IFN-alpha promotes the antiproliferaative effect of gefitinib on human colon cancer cell lines and the mechanism may be related to up-regulation expression of EGFR by IFN-alpha.
The West Indian medical journal 03/2011; 60(2):107-13. · 0.25 Impact Factor
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ABSTRACT: The regulator of cytokine signaling known as protein inhibitor of activated STAT-1 (PIAS1) is increasingly understood to have diverse regulatory functions for inflammation, but its effect in inflammatory conditions such as severe acute pancreatitis (SAP) has not previously been reported. The aim of this study was to investigate the effect of upregulation of PIAS1 on SAP associated with acute lung injury (ALI), and its subsequent effect on disease severity. Sprague-Dawley rats were given an IV injection of adenovirus serotype 5 (Ad5)/F35-PIAS1, Ad5/F35-vector or saline before induction of SAP. The control group received only a sham operation. Lung and pancreas samples were harvested 16h after induction. The protein levels of PIAS1 in tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels. The survival rates of rats were also analyzed. The results found that in Ad5/F35-PIAS1 treated rats, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels were decreased but showed no influence on the levels of IL-10, and the severity of pancreatic tissue injury was less compared with either untreated SAP or Ad5/F35-vector treated rats (P<0.01). The administration of Ad5/F35-PIAS1 in SAP-induced rats downregulated the activity of the signal transducer and activator of transcription-1 (STAT1) pathway and the expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule (ICAM)-1 protein in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased, and the survival rates increased (P<0.01). These findings suggest that PIAS1 could augment anti-inflammatory activity by inhibiting STAT1, thus attenuating the severity of SAP associated with ALI.
Cytokine 03/2011; 54(3):305-14. · 3.02 Impact Factor
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ABSTRACT: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is widely involved in cell migration, apoptosis and inflammation. However, its exact mechanisms in severe acute pancreatitis (SAP) remain unclear. The aim of this study was to explore the activity of the JAK/STAT signaling pathway in pancreatic injury, investigate the functional mechanisms of SAP in vitro, and thus elucidate the underlying therapeutic effects for SAP in vivo. The activation of the JAK-1/STAT-1 signaling pathway and the expessions of TNF-α, IL-1β and IL-6 proteins were investigated in AR42J cells induced with cerulein and treated with either PBS, RPM, or AG490. One group of cells was left untreated as a control group. Subsequently the activity of NF-κB was evaluated. Rats were given RPM or AG490 just before the induction of SAP, the severity of which was assessed at 24 h. The findings revealed that the up-regulated expressions of JAK-1/STAT-1, STAT-3 protein were closely correlated with the transcription of TNF-α, IL-1β, and IL-6 in cerulein-stimulated cells. Administration of RPM or AG490 decreased the activity of NF-κB and inhibited the release of TNF-α, IL-1β, and IL-6. The reflective markers of severity of SAP were also decreased by RPM or AG490 treatment compared to SAP rats. This study indicates that the JAK-1/STAT-1 signaling pathway activity is an early event in pancreatic inflammatory injury. Therefore, early treatment with its inhibitors might be beneficial for attenuation of pancreatic injury in SAP.
International Journal of Molecular Medicine 03/2011; 27(5):731-8. · 1.98 Impact Factor
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ABSTRACT: Our aim in this study was to investigate the changes of inflammatory response by protein inhibitor of activated signal transducer and activator of transcription 1 (PIAS1) gene silencing treatment in cerulein-stimulated AR42J cells, and relate them to changes in cell injury, thus providing evidence for developing clinical therapies. This study examined the effects of cerulein on the activity of P38 mitogen activated protein kinase (P38MAPK), c-jun NH2-terminal kinase/stress-activated protein kinase and the inflammatory mediators released by PIAS1 gene-silenced AR42J cells. Consequently, the markers including DNA ladder, cell apoptotic rat, cell cycles, levels of cell cycle and apoptotic related factors were used to determine the effects of PIAS1 gene silencing on the cerulein-induced cell injury. The results indicated that in the cerulein-stimulated PIASI silencing cells, the activity of P38MAPK was enhanced, while at the same time, the levels of inflammatory mediators such as the tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and matrix metallopeptidase-9, were markedly higher than those of other cerulein-stimulated cells. Thus, the cerulein-stimulated PIASI gene-silenced cells obviously increased cell arrest in the G1/M phase by increasing P21 and P27 expression, and also induced apoptosis by regulating the P53 signaling pathway. This study suggests that the down-regulation of PIAS1 is efficacious at enhancing the expression of inflammatory mediators and inducing cell injury in acute pancreatitis (AP), thus deteriorating the severity of disease. It provides evidence that PIAS1 is a potential therapeutic target for AP.
International Journal of Molecular Medicine 10/2010; 26(4):619-26. · 1.98 Impact Factor
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ABSTRACT: Activated protein C (APC) is an anticoagulant polypeptide that plays a critical role in coagulation, inflammation and anticoagulation interactions; in addition, it decreases the mortality rate of patients with severe infectious disease. However, the exact mechanisms of these effects remain unclear. The aim of this study was to investigate the effect of APC on human umbilical vein endothelial cell apoptosis upon lipopolysaccharide (LPS) stimulation and to elucidate its underlying mechanisms. Apoptotic changes in cells were determined by examining cell ultra-structure, DNA fragmentation and Annexin V/PI staining. Cell viability and the expression of apoptotic-related factors were measured in LPS-stimulated cells with and without APC treatment. The results showed that the administration of APC decreased the apoptosis of cells by inhibiting the activity of the caspase-3 apoptotic-signaling pathway in LPS-stimulated cells. This study supports the notion that APC treatment may be beneficial for the attenuation of endothelial cell injury caused by severe infectious disease via the regulation of apoptotic pathways. Furthermore, APC may be useful in the treatment of infectious disease.
Molecular Medicine Reports 3(6):991-7. · 0.42 Impact Factor
