Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. 相似文献
The colour stability of juice and purées made from a mixture of two strawberry varieties, stored at + 20°C or at –20°C under aerobic and anaerobic conditions, was studied. High-performance liquid chromatography and spectrophotometric analysis were used to monitor the changes in colour during storage. Pelargonidin 3-glucoside comprised 80% of the total anthocyanin content. Four other pelargonidin-based peaks were found, being 10.4%, 3.5%, 0.7% and 0.3% of the total and two cyanidin peaks were present, being 3.3% and 0.4% of the total. Clarification before storage caused considerable losses in the initial anthocyanin concentrations. Storage conditions (air versus nitrogen) did not influence the rate of loss of anthocyanins during storage or the formation of polymeric pigments. There were no losses in anthocyanins and no increase in the amount of colour measured at 510 nm due to polymers in samples stored at–20°C. Polymerisation occurred in the samples stored at + 20°C, especially in the clarified samples. 相似文献
Boron-doped diamond (BDD) electrodes were studied with respect to the formation of inorganic by-products in water electrolysis. Experiments in non-divided cells were performed with systems containing sulphate, chloride, chlorite, chlorate and nitrate ions. Discontinuous experiments in thermostated cells with rotating disk diamond anodes and expanded mesh IrO2 cathodes were carried out at 20 °C. Current density was varied between 50 and 300 A m−2. Ion chromatography was mainly used for species detection.
It was not possible to demonstrate the decomposition of sulphate although a slight tendency seems to exist in some experiments. Hydrogen peroxide is one of the anodic and cathodic by-products. Active chlorine is detectable at higher chloride concentrations compared with the use of mixed oxide anodes (MIO). One reason for this is the reaction of formed chlorine with ozone or hydrogen peroxide. Chlorate can be formed electrolysing chloride, hypochlorite and chlorite solutions. Perchlorate formation was detected. Cathodic processes are responsible for the formation of nitrite ions and ammonia. If chlorine is present, the formation of monochloramine is one possible side reaction. Results show that the processes are very complex. Reaction spectra may vary from case to case. Perchlorate formation is a high risk in drinking water treatment. 相似文献
Politicians and policy-makers, as well as modellers, often nurses an expectation that model derived results is an objective
source of information that can be used to support decisions. However, several prerequisites have to be dealt with in order
to ensure that models can be used as legitimate and efficient tools in water resource management. Based on empirical material
from recent studies on the use of models in stakeholder dialogues, mainly focusing on catchment nutrient transport, two central
problems are identified: (a) Models are laden with choices and thus depend on assumptions and priorities of modellers. (b)
There are several factors that influence ability and willingness of stakeholders (as information recovers) to criticize or
accept results of the modelling exercise. Recognized factors likely to influence stakeholders' acceptance of model derived
results include issues at stake, stakeholders' ability to criticize model derived information, and their trust in the institutions
that have developed or applied the used models. Identified prerequisites for successful use of models in integrated water
resource management include: consideration of user relevance, awareness of and preparedness to handle constraints linked to
communication of model-based results, transparency of used models and data and of involved uncertainties, mutual respect between
experts and stakeholders and between involved stakeholder groups, a robust institutional network, and sufficient time for
dialogues. Development and use of strategies for participatory modelling, based on a continuous dialogue between experts and
stakeholders is recommended as a way to facilitate that the prerequisites for a successful use of models in water resource
management are fulfilled. 相似文献
The distribution of anthocyanins in methanolic skin extracts of 16 grape cultivars used for port wine production and grown at five sites in the Douro Valley in Northern Portugal has been assessed by high performance liquid chromatography. Results are confined to the seven most readily separated and identified anthocyanins and are expressed as percentages of their total (88–99% of the total integrated area). Anthocyanins based on malvidin (Mv) predominated. Of these, Mv 3-glucoside was the major pigment (33–60%), being exceeded by Mv 3-p-coumarylglucoside (2–51%) in only two cultivars; Mv 3-acetylglucoside (1–15%) was consistently the lowest. Peonidin 3-glucoside (1–27%) was prominent in four cultivars, but delphinidin 3-glucoside (1–11%), petunidin 3-glucoside (2–11%) and cyanidin 3-glucoside (trace-6%) were of low proportions throughout. The ratio Mv 3-acetylglucoside/total Mv glucosides appeared characteristic of cultivar, independent of site, and a useful aid to identification of grape cultivars. The coloured pulp of some cultivars contained peonidin 3-glucoside as a major component, present in greater proportions than in the skin; the percentage of Mv 3-p-coumarylglucoside was lower in pulp than in skin. The identities of six of the seven anthocyanins were confirmed by fast atom bombardment mass spectrometry and the structures of the Mv derivatives were determined by nuclear magnetic resonance. The formation of formyl and acetyl anthocyanin artefacts is described. 相似文献
The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1, 2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in Hif-p4h-1−/−, Hif-p4h-2 hypomorph and Hif-p4h-3−/− mice. Only Hif-p4h-2 hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs. 相似文献
This paper describes the kinetics of attrition in the bubbling zone of a fluidized bed and focuses on the development of an equation for attrition in continuous fluidized beds operating at steady state.
Laboratory data describing batch attrition of a limestone sorbent are applied to the integrated equations to describe overall attrition rate in a full-scale continuous system. 相似文献