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ABSTRACT: Dracorhodin perchlorate has been recently shown to induce apoptotic cell death in cancer cells. However, the molecular mechanisms underlying these effects are unknown in human gastric tumor cells. In this study, effects of Dracorhodin perchlorate on cell viability, cell cycle, and apoptosis were investigated in SGC-7901 cells. The results showed that Dracorhodin perchlorate induced cellular and DNA morphological changes and decreased the viability of SGC-7901 cells. Dracorhodin perchlorate-mediated cell cycle arrest was associated with a marked decrease in protein levels of phosphorylated retinoblastoma and E2F1. Dracorhodin perchlorate-induced apoptosis is mediated via upregulation of p53, inhibiting the activation of PI3K/Akt, and NF-κB, thereby decreasing the expression of the anti-apoptotic proteins, Bcl-2 and Bcl-XL. Interestingly, we also found that Dracorhodin perchlorate significantly suppressed the IGF-1-induced phosphorylation of Akt in the stably expressing EGFP-Akt recombinant CHO-hIR cells and inhibited TNF-induced NF-κB transcriptional activity in the NF-κBp65-EGFP recombinant U2OS cells, indicating that inhibition of PI3K/Akt and NF-κB may provide a molecular basis for the ability of Dracorhodin perchlorate to induce apoptosis. Dracorhodin perchlorate induced up-regulation of p53, thereby resulting in the activation of its downstream targets p21 and Bax following the dissipation of mitochondrial membrane potential and activation of caspase-3 and its substrate, PARP. Moreover, Dracorhodin perchlorate dramatically enhanced the wortmannin- and TNF-induced apoptosis in SGC-7901 cells. These results reveal functional interplay among the PI3K/Akt, p53 and NF-κB pathways that are frequently deregulated in cancer and suggest that their simultaneous targeting by Dracorhodin perchlorate could result in efficacious and selective killing of cancer cells.
Apoptosis 06/2012; 17(10):1104-19. · 4.07 Impact Factor
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ABSTRACT: Dracorhodin perchlorate has been recently shown to induce apoptotic cell death in cancer cells. However, the molecular mechanisms underlying these effects are unknown in human gastric tumor cells. In this study, effects of Dracorhodin perchlorate on cell viability, cell cycle, and apoptosis were investigated in SGC-7901 cells. The results showed that Dracorhodin perchlorate induced cellular and DNA morphological changes and decreased the viability of SGC-7901 cells. Dracorhodin perchlorate-mediated cell cycle arrest was associated with a marked decrease in protein levels of phosphorylated retinoblastoma and E2F1. Dracorhodin perchlorate-induced apoptosis is mediated via upregulation of p53, inhibiting the activation of PI3K-Akt, and NF-κB, thereby decreasing the expression of the anti-apoptotic proteins, Bcl-2 and Bcl-XL. Interestingly, we also found that Dracorhodin perchlorate significantly suppressed the IGF-1-induced phosphorylation of Akt in the stably expressing EGFP-Akt recombinant CHO-hIR cells and inhibited TNF-induced NF-κB transcriptional activity in the NF-κBp65-EGFP recombinant U2OS cells, indicating that inhibition of PI3K/Akt and NF-κB may provide a molecular basis for the ability of Dracorhodin perchlorate to induce apoptosis. Dracorhodin perchlorate induced up-regulation of p53, thereby resulting in the activation of its downstream targets p21 and Bax following the dissipation of mitochondrial membrane potential and activation of caspase-3 and its substrate, PARP. Moreover, Dracorhodin perchlorate dramatically enhanced the wortmannin- and TNF-induced apoptosis in SGC-7901 cells. These results reveal functional interplay among the PI3K/AKT, p53 and NF-κB pathways that are frequently deregulated in cancer and suggest that their simultaneous targeting by Dracorhodin perchlorate could result in efficacious and selective killing of cancer cells.
APOPTOSIS 05/2012; · 4.79 Impact Factor
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ABSTRACT: The incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplantation (LT) patients are at higher risk for acquiring CDI. Small, single-center studies (but no nationwide analyses) have assessed this association. We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (2004-2008) for this retrospective, cross-sectional study. Patients with any discharge diagnosis of LT composed the study population, and they were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were the prevalence of CDI and the effects of CDI on inpatient mortality. Our secondary outcomes included the length of stay and hospitalization charges. A regression analysis was used to derive odds ratios (ORs) adjusted for potential confounders. There were 193,174 discharges with a diagnosis of LT from 2004 to 2008. The prevalence of CDI was 2.7% in the LT population and 0.9% in the non-LT population (P < 0.001). Most of the LT patients were 50 to 64 years old. LT patients had higher odds of developing CDI [OR = 2.88, 95% confidence interval (CI) = 2.68-3.10]. Increasing age and increasing comorbidity (including inflammatory bowel disease and nasogastric tube placement) were also independent CDI risk factors. CDI was associated with a higher mortality rate: 5.5% for LT patients with CDI versus 3.2% for LT-only patients (adjusted OR = 1.70, 95% CI = 1.29-2.25). In conclusion, the prevalence of CDI is higher for LT patients versus non-LT patients (2.7% versus 0.9%). CDI is an independent risk factor for mortality in the LT population.
Liver Transplantation 04/2012; 18(8):972-8. · 3.39 Impact Factor
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ABSTRACT: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB).
We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling.
In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17-1.46) and 1.84 (95% CI 1.61-2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21-1.78) and 3.02 (95% CI 2.23-4.1), respectively.
Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians.
American Journal of Nephrology 02/2012; 35(3):216-24. · 2.54 Impact Factor
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ABSTRACT: To determine the role of duplex Doppler ultrasonography (DDU) in patients with acute unilateral renal obstruction.
A total of 161 patients with suspected renal colic due to urolithiasis were evaluated by DDU followed by intravenous urography (IVU). The mean intra-arterial resistive index (RI) and the difference of mean resistive index between both kidneys (delta RI) were determined for each person. An RI value of ≥0.70 and a delta RI value of ≥0.06 were taken as the discriminatory threshold for obstruction. IVU results were considered the " reference standard" against which renal DDU findings were compared.
IVU showed both kidneys to be normal in 51 patients and with unilateral ureteric obstruction in 110 patients. The mean RI for obstructed kidneys was 0.67 (0.048), which was significantly higher (P-value <0.05) than a mean RI of contralateral normal kidneys 0.59 (0.04). The mean delta RI in patients with unilateral ureteric obstruction was significantly higher than that in patients with normal kidneys, at 0.076 (0.03) and 0.03 (0.05), respectively. In patients with complete obstruction, sensitivity of RI and delta RI were 77.5% and 92.5% with a specificity of 84.3% and 90.1%, respectively. In patients with partial obstruction, the sensitivity of these values was 22.8% and 62.8% with a specificity of 84.3% and 90.1%.
Delta RI is more sensitive and specific than RI in acute renal obstruction. However, due to relatively low sensitivity for detection of partial obstruction, DDU cannot replace IVU as the standard imaging technique.
International Journal of Nephrology and Renovascular Disease 01/2012; 5:15-21.
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ABSTRACT: he study was designed to find novel and targeted anticancer compounds from the Chinese herbs. For this purpose, we screened the ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was also one of them that showed potential cytotoxic activity. The target compound isolated from it and analyzed on analytical HPLC. The chromatogram showed that there was only one peak and the purity was 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and Nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanism involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells was examined for the first time. The mixture of compounds 1 and 2 triggered the mitochondrial apoptotic pathway, as demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased by the mixture of compounds 1 and 2. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 was mainly due to induction of cell cycle arrest and apoptosis.
Asian Pacific journal of cancer prevention: APJCP 01/2011; 12. · 0.66 Impact Factor
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ABSTRACT: Isoalantolactone, a sesquiterpene lactone possesses anti-fungal as well as cytotoxic properties. In this study the effects of Isoalantolactone over the cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone induced morphological changes and decreased the cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with decreased in the expression level of cyclin B1 and cdc 25c. Isoalantolactone triggered apoptosis was verified by propidium iodide (PI) and annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (ΔΨm) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which give the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound.
Archives of Pharmacal Research 01/2011; · 1.59 Impact Factor
