Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling

Cordycepin, the major active component from Cordyceps militaris, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found that Dkk1 overexpression by transfection downregulated the expression of c-Myc and cyclin D1. siRNA-mediated Dkk1 silencing downregulated the expression of Atg8, beclin, and LC3 and promoted β-catenin translocation from the cytoplasm into the nucleus. These results suggest that cordycepin inhibits ovarian cancer cell growth, possibly through coordinated autophagy and Dkk1/β-catenin signaling. Taken together, our findings provide new insights into the treatment of ovarian cancer using cordycepin

Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes

This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes

Reactive oxygen species and p47phox activation are essential for the Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia

<p>Abstract</p> <p>Background</p> <p>Activated microglia elicits a robust amount of pro-inflammatory cytokines, which are implicated in the pathogenesis of tuberculosis in the central nervous system (CNS). However, little is known about the intracellular signaling mechanisms governing these inflammatory responses in microglia in response to <it>Mycobacterium tuberculosis </it>(Mtb).</p> <p>Methods</p> <p>Murine microglial BV-2 cells and primary mixed glial cells were stimulated with sonicated Mtb (s-Mtb). Intracellular ROS levels were measured by staining with oxidative fluorescent dyes [2',7'-Dichlorodihydrofluorescein diacetate (H₂DCFDA) and dihydroethidium (DHE)]. NADPH oxidase activities were measured by lucigenin chemiluminescence assay. S-Mtb-induced MAPK activation and pro-inflammatory cytokine release in microglial cells were measured using by Western blot analysis and enzyme-linked immunosorbent assay, respectively.</p> <p>Results</p> <p>We demonstrate that s-Mtb promotes the up-regulation of reactive oxygen species (ROS) and the rapid activation of mitogen-activated protein kinases (MAPKs), including p38 and extracellular signal-regulated kinase (ERK) 1/2, as well as the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12p40 in murine microglial BV-2 cells and primary mixed glial cells. Both NADPH oxidase and mitochondrial electron transfer chain subunit I play an indispensable role in s-Mtb-induced MAPK activation and pro-inflammatory cytokine production in BV-2 cells and mixed glial cells. Furthermore, the activation of cytosolic NADPH oxidase p47phox and MAPKs (p38 and ERK1/2) is mutually dependent on s-Mtb-induced inflammatory signaling in murine microglia. Neither TLR2 nor dectin-1 was involved in s-Mtb-induced inflammatory responses in murine microglia.</p> <p>Conclusion</p> <p>These data collectively demonstrate that s-Mtb actively induces the pro-inflammatory response in microglia through NADPH oxidase-dependent ROS generation, although the specific pattern-recognition receptors involved in these responses remain to be identified.</p

Childhood Cancer Mortality and Birth Characteristics in Korea: A National Population-based Birth Cohort Study

To examine the relationship between birth characteristics and childhood cancer mortality, a retrospective cohort study of Korean children was conducted using data collected by the national birth register between 1995 and 2006, which were then individually linked to death data. A cohort of 6,479,406 children was followed from birth until their death or until December 31, 2006. Poisson regression analyses were used to calculate rate ratios of childhood cancer deaths according to birth characteristics. A total of 1,469 cancer deaths were noted and the childhood cancer mortality rate was found to be 3.43 per 100,000 person-years in Korea during the period of 1995-2006. The birth characteristics examined in this study (i.e. , birth weight, gestational age, multiple births, parental ages, and number of siblings) were generally found to be not significantly associated with childhood cancer mortality, and the associations did not vary meaningfully with gender nor with cancer sites. However, among children aged 5-11 yr, higher birth weight was associated with elevated childhood cancer mortality (rate ratio = 1.28, 95% confidence interval 1.04-1.58). Our results offer no overall associations between childhood cancer mortality and birth characteristics, but suggest that the association may be specific to age group

Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock

Mammalian 2-Cys peroxiredoxin II (Prx II) is a cellular peroxidase that eliminates endogenous H2O2. The involvement of Prx II in the regulation of lipopolysaccharide (LPS) signaling is poorly understood. In this report, we show that LPS induces substantially enhanced inflammatory events, which include the signaling molecules nuclear factor κB and mitogen-activated protein kinase (MAPK), in Prx II–deficient macrophages. This effect of LPS was mediated by the robust up-regulation of the reactive oxygen species (ROS)–generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and the phosphorylation of p47phox. Furthermore, challenge with LPS induced greater sensitivity to LPS-induced lethal shock in Prx II–deficient mice than in wild-type mice. Intravenous injection of Prx II–deficient mice with the adenovirus-encoding Prx II gene significantly rescued mice from LPS-induced lethal shock as compared with the injection of a control virus. The administration of catalase mimicked the reversal effects of Prx II on LPS-induced inflammatory responses in Prx II–deficient cells, which suggests that intracellular H2O2 is attributable, at least in part, to the enhanced sensitivity to LPS. These results indicate that Prx II is an essential negative regulator of LPS-induced inflammatory signaling through modulation of ROS synthesis via NADPH oxidase activities and, therefore, is crucial for the prevention of excessive host responses to microbial products

Biochemical Markers as Predictors of In-Hospital Mortality in Patients with Severe Trauma: A Retrospective Cohort Study

Background Initial evaluation of injury severity in trauma patients is an important and challenging task. We aimed to assess whether easily measurable biochemical parameters (hemoglobin, pH, and prothrombin time/international normalized ratio [PT/INR]) can predict in-hospital mortality in patients with severe trauma. Methods This retrospective study involved review of the medical records of 315 patients with severe trauma and an injury severity score >15 who were managed at Gyeongsang National University Hospital between January 2005 and December 2015. We extracted the following data: in-hospital mortality, injury severity score, and initial hemoglobin level, pH, and PT/INR. The predictive values of these variables were compared using receiver operation characteristic curves. Results Of the 315 patients, 72 (22.9%) died. The in-hospital mortality rates of patients with hemoglobin levels <8.4 g/dl and ≥8.4 g/dl were 49.8% and 9.9%, respectively (P < 0.001). At a cutoff hemoglobin level of 8.4 g/dl, the sensitivity and specificity values for mortality were 81.9% and 86.4%, respectively. At a pH cutoff of 7.25, the sensitivity and specificity values for mortality were 66.7% and 77.8%, respectively; 66.7% of patients with a pH <7.25 died versus 22.2% with a pH ≥7.25 (P < 0.001). The in-hospital mortality rates for patients with PT/INR values ≥1.4 and <1.4 were 37.5% and 16%, respectively (P < 0.001; sensitivity, 37.5%; specificity, 84%). Conclusions Using the suggested cutoff values, hemoglobin level, pH, and PT/INR can simply and easily be used to predict in-hospital mortality in patients with severe trauma

Nonimmunity against hepatitis B virus infection in patients newly diagnosed with inflammatory bowel disease

Background/AimsThis study aimed to elucidate the prevalence of hepatitis B virus (HBV) serologic markers in Korean patients newly diagnosed with, but not yet treated for inflammatory bowel disease (IBD).MethodsWe prospectively enrolled 210 patients newly diagnosed with IBD (109 with ulcerative colitis and 101 with Crohn's disease). Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were measured and compared with those of 1,100 sex- and age-matched controls.ResultsThe prevalence of chronic HBV infection (positive HBsAg, positive anti-HBc, and negative anti-HBs results) and past infection (negative HBsAg, positive anti-HBc, and positive or negative anti-HBs results) were not significantly different between the patients and controls (chronic HBV infection: IBD, 3.8% vs. control, 4.9%, P=0.596; past infection: IBD, 26.2% vs. control, 28.8%, P=0.625). The patients with IBD aged <20 years were at a higher susceptibility risk (nonimmune) for HBV infection than the controls (IBD, 41.5% vs. control, 22.4%; P=0.018). In the multivariate analysis, an age of <20 years (P=0.024) and symptom duration of ≥12 months before diagnosis (P=0.027) were identified as independent risk factors for nonimmunity against HBV infection.ConclusionsThe patients newly diagnosed with IBD were susceptible to HBV infection. The frequency of nonimmunity was high, especially in the patients aged <20 years and those with a longer duration of symptoms before diagnosis. Therefore, it is necessary to screen for HBV serologic markers and generate a detailed vaccination plan for patients newly diagnosed with IBD

Antibiotic susceptibility and imaging findings of the causative microorganisms responsible for acute urinary tract infection in children: a five-year single center study

PurposeWe studied the differences in the antibiotic susceptibilities of the microorganisms that causeing urinary tract infections (UTI) in children to obtain useful information on appropriate drug selection for childhood UTI.MethodsWe retrospectively analyzed the antibiotic susceptibilities of 429 microorganisms isolated from 900 patients diagnosed with UTI in the Department of Pediatrics, Chungbuk National University Hospital, from 2003 to 2008.ResultsThe most common causative microorganisms for UTI were Escherichia coli (81.4%), Klebsiella pneumoniae (8.4%), Enterobacter spp. (1.7%), and Proteus spp. (0.4%). E. coli showed relatively high susceptibility as compared to imipenem (100%), amikacin (97.7%), aztreonam (97.9%), cefepime (97.7%), and ceftriaxone (97.1%), while it showed relatively low susceptibility to gentamicin (GM) (79.0%), trimethoprim/sulfamethoxazole (TMP/SMX) (68.7%), ampicillin/sulbactam (33.0%), and ampicillin (AMP) (28.6%). There were no significant differences in the image findings for causative microorganisms.ConclusionGram-negative organisms showed high susceptibility to amikacin and third-generation cephalosporins, and low susceptibility to AMP, GM, and TMP/SMX. Therefore, the use of AMP or TMP/SMX as the first choice in empirical and prophylactic treatment of childhood UTI in Korea should be reconsidered and investigated further