LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>As EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A) in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY), a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719.</p> <p>Methods</p> <p>After single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT.</p> <p>Results</p> <p>When 5-FU was sequentially combined with LY, the combination index (CI) value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NFκB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NFκB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (%) increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone.</p> <p>Conclusion</p> <p>These data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance of 5-FU via downregulation of activated p-AKT and mitochondria-dependent apoptosis in EBV gastric cancer cell line, SNU-719.</p

Dopamine Agonists and their risk to induce psychotic episodes in Parkinson's disease: a case-control study

<p>Abstract</p> <p>Background</p> <p>Psychosis is rare in untreated patients with Parkinson's disease (PD) but the prevalence rises to 40% during dopaminergic treatment. So far, no systematic comparison of the psychogenic potential of different dopaminergic drugs had been performed.</p> <p>Methods</p> <p>Eighty PD patients with psychotic episodes were compared to an age-matched control group of PD patients without psychotic episodes (n = 120) in a cross-sectional retrospective study.</p> <p>Results</p> <p>We found a positive correlation between psychotic episodes and dementia, number of concomitant medication, and pergolide intake. Odds ratio calculation confirmed the association with dementia. With respect to dopaminergic treatment, pergolide showed the highest odds ratio, levodopa the lowest. An adjusted logistic regression model confirmed the strong association with psychotic episodes and pergolide and no association with levodopa (adjusted odds ratio 2.01 and 0.11, respectively).</p> <p>Conclusion</p> <p>The analysis indicates that dementia and concomitant medication are factors in PD associated with psychotic symptoms. Furthermore, different dopaminergic drugs showed markedly different associations with psychotic symptoms</p

A comparison of the Charlson comorbidity index derived from medical records and claims data from patients undergoing lung cancer surgery in Korea: a population-based investigation

<p>Abstract</p> <p>Background</p> <p>Calculating the Charlson comorbidity index (CCI) from medical records is a time-consuming and expensive process. The objectives of this study are to 1) measure agreement between medical record and claims data for CCI in lung cancer patients and 2) predict health outcomes of lung cancer patients based on CCIs from both data sources.</p> <p>Methods</p> <p>We studied 392 patients who underwent surgery for pathologic stages I-III of lung cancer. The kappa value was used to measure the agreement between the 17 comorbidities of the CCI prevalence obtained from medical records and claims data. Multiple linear regression analyses were used to evaluate the relationships between CCI and length of stay and reimbursement cost.</p> <p>Results</p> <p>Out of 17 comorbidities identified in the Charlson comorbidity index, ten had a higher prevalence, four had a lower prevalence and three had a similar prevalence in claims data to those of medical records. The kappa values calculated from the two databases ranged from 0.093 to 0.473 for nine comorbidities. In predicting length of stay and reimbursement cost after surgical resection for lung cancer patients, the CCI scores derived from both the medical records and claims data were not statistically significant.</p> <p>Conclusions</p> <p>Poor agreement between medical record data and claims data may result from different motivations for collecting data. Further studies are needed to determine an appropriate method for predicting health outcomes based on these data sources.</p

Framing the challenge of climate change in Nature and Science editorials

Through their editorialising practices, leading international science journals such as Nature and Science interpret the changing roles of science in society and exert considerable influence on scientific priorities and practices. Here we examine nearly 500 editorials published in these two journals between 1966 and 2016 which deal with climate change, thereby constructing a lens through which to view the changing engagement of science and scientists with the issue. A systematic longitudinal frame analysis reveals broad similarities between Nature and Science in the waxing and waning of editorialising attention given to the topic. But although both journals have diversified how they frame the challenges of climate change, they have done so in different ways. We attribute these differences to three influences: the different political and epistemic cultures into which they publish; their different institutional histories; and their different editors and editorial authorship practices

Using spatial analysis to demonstrate the heterogeneity of the cardiovascular drug-prescribing pattern in Taiwan

<p>Abstract</p> <p>Background</p> <p>Geographic Information Systems (GIS) combined with spatial analytical methods could be helpful in examining patterns of drug use. Little attention has been paid to geographic variation of cardiovascular prescription use in Taiwan. The main objective was to use local spatial association statistics to test whether or not the cardiovascular medication-prescribing pattern is homogenous across 352 townships in Taiwan.</p> <p>Methods</p> <p>The statistical methods used were the global measures of Moran's <it>I </it>and Local Indicators of Spatial Association (LISA). While Moran's <it>I </it>provides information on the overall spatial distribution of the data, LISA provides information on types of spatial association at the local level. LISA statistics can also be used to identify influential locations in spatial association analysis. The major classes of prescription cardiovascular drugs were taken from Taiwan's National Health Insurance Research Database (NHIRD), which has a coverage rate of over 97%. The dosage of each prescription was converted into defined daily doses to measure the consumption of each class of drugs. Data were analyzed with ArcGIS and GeoDa at the township level.</p> <p>Results</p> <p>The LISA statistics showed an unusual use of cardiovascular medications in the southern townships with high local variation. Patterns of drug use also showed more low-low spatial clusters (cold spots) than high-high spatial clusters (hot spots), and those low-low associations were clustered in the rural areas.</p> <p>Conclusions</p> <p>The cardiovascular drug prescribing patterns were heterogeneous across Taiwan. In particular, a clear pattern of north-south disparity exists. Such spatial clustering helps prioritize the target areas that require better education concerning drug use.</p

A Putative Transcription Factor MYT2 Regulates Perithecium Size in the Ascomycete Gibberella zeae

The homothallic ascomycete fungus Gibberella zeae is a plant pathogen that is found worldwide, causing Fusarium head blight (FHB) in cereal crops and ear rot of maize. Ascospores formed in fruiting bodies (i.e., perithecia) are hypothesized to be the primary inocula for FHB disease. Perithecium development is a complex cellular differentiation process controlled by many developmentally regulated genes. In this study, we selected a previously reported putative transcription factor containing the Myb DNA-binding domain MYT2 for an in-depth study on sexual development. The deletion of MYT2 resulted in a larger perithecium, while its overexpression resulted in a smaller perithecium when compared to the wild-type strain. These data suggest that MYT2 regulates perithecium size differentiation. MYT2 overexpression affected pleiotropic phenotypes including vegetative growth, conidia production, virulence, and mycotoxin production. Nuclear localization of the MYT2 protein supports its role as a transcriptional regulator. Transcriptional analyses of trichothecene synthetic genes suggest that MYT2 additionally functions as a suppressor for trichothecene production. This is the first study characterizing a transcription factor required for perithecium size differentiation in G. zeae, and it provides a novel angle for understanding sexual development in filamentous fungi

Great Genetic Differentiation among Populations of Meconopsis integrifolia and Its Implication for Plant Speciation in the Qinghai-Tibetan Plateau

The complex tectonic events and climatic oscillations in the Qinghai-Tibetan Plateau (QTP), the largest and highest plateau in the world, are thought to have had great effects on the evolutionary history of the native plants. Of great interest is to investigate plant population genetic divergence in the QTP and its correlation with the geologic and climatic changes. We conducted a range-wide phylogeographical analysis of M. integrifolia based on the chloroplast DNA (cpDNA) trnL-trnF and trnfM-trnS regions, and defined 26 haplotypes that were phylogenetically divided into six clades dated to the late Tertiary. The six clades correspond, respectively, to highly differentiated population groups that do not overlap in geographic distribution, implying that the mountain ranges acting as corridors or barriers greatly affected the evolutionary history of the QTP plants. The older clade of M. integrifolia only occurs in the southwest of the species' range, whereas the distributions of younger clades extend northeastward in the eastern QTP, suggesting that climatic divergence resulting from the uplift of the QTP triggered the initial divergence of M. integrifolia native to the plateau. Also, the nrDNA ITS region was used to clarify the unexpected phylogenetic relationships of cpDNA haplotypes between M. integrifolia and M. betonicifolia. The topological incongruence between the two phylogenies suggests an ancestral hybridization between the two species. Our study indicates that geographic isolation and hybridization are two important mechanisms responsible for the population differentiation and speciation of Meconopsis, a species-rich genus with complex polyploids

Burial Depth and Stolon Internode Length Independently Affect Survival of Small Clonal Fragments

Disturbance can fragment plant clones into different sizes and unstabilize soils to different degrees, so that clonal fragments of different sizes can be buried in soils at different depths. As a short-term storage organ, solon internode may help fragmented clones of stoloniferous plants to withstand deeper burial in soils. We address (1) whether burial in soils decreases survival and growth of small clonal fragments, and (2) whether increasing internode length increases survival and growth of small fragments under burial. We conducted an experiment with the stoloniferous, invasive herb Alternanthera philoxeroides, in which single-node fragments with stolon internode of 0, 2, 4 and 8 cm were buried in soils at 0, 2, 4 and 8 cm depth, respectively. Increasing burial depth significantly reduced survival of the A. philoxeroides plants and increased root to shoot ratio and total stolon length, but did not change growth measures. Increasing internode length significantly increased survival and growth measures, but there was no interaction effect with burial depth on any traits measured. These results indicate that reserves stored in stolon internodes can contribute to the fitness of the A. philoxeroides plants subject to disturbance. Although burial reduced the regeneration capacity of the A. philoxeroides plants, the species may maintain the fitness by changing biomass allocation and stolon length once it survived the burial. Such responses may play an important role for A. philoxeroides in establishment and invasiveness in frequently disturbed habitats

Understanding Plant-Microbe Interactions for Phytoremediation of Petroleum-Polluted Soil

Plant-microbe interactions are considered to be important processes determining the efficiency of phytoremediation of petroleum pollution, however relatively little is known about how these interactions are influenced by petroleum pollution. In this experimental study using a microcosm approach, we examined how plant ecophysiological traits, soil nutrients and microbial activities were influenced by petroleum pollution in Phragmites australis, a phytoremediating species. Generally, petroleum pollution reduced plant performance, especially at early stages of plant growth. Petroleum had negative effects on the net accumulation of inorganic nitrogen from its organic forms (net nitrogen mineralization (NNM)) most likely by decreasing the inorganic nitrogen available to the plants in petroleum-polluted soils. However, abundant dissolved organic nitrogen (DON) was found in petroleum-polluted soil. In order to overcome initial deficiency of inorganic nitrogen, plants by dint of high colonization of arbuscular mycorrhizal fungi might absorb some DON for their growth in petroleum-polluted soils. In addition, through using a real-time polymerase chain reaction method, we quantified hydrocarbon-degrading bacterial traits based on their catabolic genes (i.e. alkB (alkane monooxygenase), nah (naphthalene dioxygenase) and tol (xylene monooxygenase) genes). This enumeration of target genes suggests that different hydrocarbon-degrading bacteria experienced different dynamic changes during phytoremediation and a greater abundance of alkB was detected during vegetative growth stages. Because phytoremediation of different components of petroleum is performed by different hydrocarbon-degrading bacteria, plants’ ability of phytoremediating different components might therefore vary during the plant life cycle. Phytoremediation might be most effective during the vegetative growth stages as greater abundances of hydrocarbon-degrading bacteria containing alkB and tol genes were observed at these stages. The information provided by this study enhances our understanding of the effects of petroleum pollution on plant-microbe interactions and the roles of these interactions in the phytoremediation of petroleum-polluted soil