Requirement of estrogen receptor alpha DNA-binding domain for HPV oncogene-induced cervical carcinogenesis in mice

Cervical cancer is caused by human papillomavirus (HPV) in collaboration with other non-viral factors. The uterine cervix is hormone responsive and female hormones have been implicated in the pathogenesis of the disease. HPV transgenic mice expressing HPV16 oncogenes E6 ( K14E6 ) and/or E7 ( K14E7 ) have been employed to study a mechanism of estrogen and estrogen receptor ? (ER?) in cervical carcinogenesis. A chronic exposure to physiological levels of exogenous estrogen leads to cervical cancer in the HPV transgenic mice, which depends on ER?. The receptor is composed of multiple functional domains including a DNA-binding domain (DBD), which mediates its binding to estrogen-responsive elements (EREs) on target genes. A transcriptional control of genes by ER? is mediated by either DBD-dependent (classical) or DBD-independent (non-classical) pathway. Although molecular mechanisms of ER? in cancer have been characterized extensively, studies investigating importance of each pathway for carcinogenesis are scarce. In this study, we employ knock-in mice expressing an ER? DBD mutant (E207A/G208A) that is defective specifically for ERE binding. We demonstrate that the ER? DBD mutant fails to support estrogen-induced epithelial cell proliferation and carcinogenesis in the cervix of K14E7 transgenic mice. We also demonstrate that cervical diseases are absent in K14E7 mice when one ER? DBD mutant allele and one wild-type allele are present. We conclude that the ER? classical pathway is required for cervical carcinogenesis in a mouse model

The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B

BackgroundApolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults.MethodsWe analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations.ResultsThe mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5±4.6 mg/dL vs. 31.2±4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956).ConclusionCompared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties

Breakdown of the interlayer coherence in twisted bilayer graphene

Coherent motion of the electrons in the Bloch states is one of the fundamental concepts of the charge conduction in solid state physics. In layered materials, however, such a condition often breaks down for the interlayer conduction, when the interlayer coupling is significantly reduced by e.g. large interlayer separation. We report that complete suppression of coherent conduction is realized even in an atomic length scale of layer separation in twisted bilayer graphene. The interlayer resistivity of twisted bilayer graphene is much higher than the c-axis resistivity of Bernal-stacked graphite, and exhibits strong dependence on temperature as well as on external electric fields. These results suggest that the graphene layers are significantly decoupled by rotation and incoherent conduction is a main transport channel between the layers of twisted bilayer graphene.Comment: 5 pages, 3 figure

Association of timed up and go test outcomes with future incidence of cardiovascular disease and mortality in adults aged 66 years: Korean national representative longitudinal study over 5.7 years

The timed up and go test (TUG) is one of the most widely used tests of mobility. We aimed to examine whether the TUG is associated with cardiovascular (CV) events, CV mortality, and all-cause mortality. Subjects in the senior cohort database of the Korean National Health Insurance Service (2002–2013) who completed the TUG as part of the National Screening Program for Transitional Ages (NSPTA) during 2007–2008 were identified. An abnormal TUG result was defined as a time ≥ 10 s. Cox proportional hazard models were used to assess the associations between TUG results and CV events, CV mortality, and all-cause mortality. The mean follow-up period was 5.7 years. Incidence rates of CV events in the normal and abnormal TUG groups were 7.93 and 8.98 per 1000 person-years, while CV mortality rates were 0.96 and 1.51 per 1000 person-years, respectively. In a fully adjusted model, we found that abnormal TUG results were not associated with the incidences of CV events and CV mortality. However, abnormal TUG results (≥10 s) resulted in a 2.9-fold increase in CV mortality in women (adjusted hazard ratio 2.90, 95% confidence interval 1.15–7.30). Further, participants lacking certain CV risk factors, such as current cigarette smoking, obesity, or diabetes, had a higher CV mortality rate when TUG results were abnormal. Abnormal TUG results in subjects aged 66 years were associated with future CV mortality in women and in subjects without obesity, diabetes, or cigarette smoking. In patient with mobility impairment, physicians should consider CV disease risk, especially in women.This study was supported by the Hammi Group [0620140890 (2013–2607)], Seoul, Korea. The funder had no role in the design or conduct of the stud

Protective Effects of Platycodon grandiflorum Aqueous Extract on Thioacetamide-induced Fulminant Hepatic Failure in Mice

The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure

Airway obstruction by extrinsic tracheal compression during spinal surgery under prone position -A case report-

Tracheal compression by vascular anomalies in adults is uncommon and most related reports are of children. A 79-year-old woman without any respiratory history underwent a lumbar spine surgery under general anesthesia. She suddenly developed airway obstruction after a position change from supine to prone. A fiberoptic bronchoscopy showed the obstruction of endotracheal tube. The obstruction was relieved after we changed the depth of endotracheal tube and supported the patient's neck with a cotton roll. The surgery ended without any other event and the patient recovered safely. A computed tomography revealed the rightward tracheal deviation and tortuous innominate artery contact with trachea. The patient didn't manifest any respiratory related symptoms during postoperative period, and she was discharged without any treatment