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Anne-Margarethe Enge Florian Kaltner Christoph Gottschalk Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(8)
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. 相似文献
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Stefanie Vanbecelaere Katrien Van den Berghe Frederik Cornillie Delphine Sasanguie Bert Reynvoet Fien Depaepe 《Journal of Computer Assisted Learning》2020,36(4):502-513
For the training of academic skills, digital educational games with integrated adaptivity are promising. Adaptive games are considered superior to non-adaptive games, because they constantly assess children's performance, and accordingly adapt the difficulty of the tasks corresponding to the children's individual level. However, empirical evidence with regard to the effectivity of adaptive compared to non-adaptive games is limited. A study was conducted with 191 children from the third year of Kinder garten who were enrolled in one of three conditions, that is, playing an adaptive version of the reading game (RG), a non-adaptive version of the RG or training with pen-and-paper exercises. In all three conditions, children trained emergent reading (phonological awareness and letter knowledge) once a week for 30 min over a period of 5 weeks. Children's performance on cognitive (phonological awareness, letter knowledge, reading fluency) and non-cognitive (motivation, self-concept) factors was assessed. Results revealed a significant improvement in phonological awareness and letter knowledge in all conditions. However, no differences between the conditions were observed with respect to children's improvement on phonological awareness and letter knowledge or on their post-test scores for reading fluency. With regard to motivation and self-concept, again, no differences in these non-cognitive factors were observed across conditions. 相似文献
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High‐intensity sweeteners in espresso coffee: ideal and equivalent sweetness and time–intensity analysis 下载免费PDF全文
Bruna M. Azevedo Flávio L. Schmidt Helena M. A. Bolini 《International Journal of Food Science & Technology》2015,50(6):1374-1381
The efficient substitution of sucrose by a sweetener in beverages requires the application of some sensory techniques. First, one must determine the concentrations of the sweeteners under study, equivalent in sweetness to the ideal sucrose concentration. In addition, it is fundamental to determine which is most similar to sucrose. The objectives of this study were to determine the ideal sweetness for espresso coffee and the equivalent concentrations in sweetness of different sweeteners, as well as characterise the time–intensity profile of each sweetener in relation to sweetness. The sweeteners evaluated were sucralose, aspartame, neotame, a cyclamate/saccharin mixture (2:1) and stevia. The sucrose concentration considered ideal by consumers was 12.5% (w/v), and the equivalent concentrations of the sweeteners were 0.0159% for sucralose, 0.0549% for aspartame, 0.0016% for neotame, 0.0359% for the cyclamate/saccharin mixture and 0.0998% for stevia. The time–intensity analysis indicated that possibly the sweeteners neotame, aspartame and sucralose would be the best substitutes for sucrose. 相似文献
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Freddy A. Bernal Dr. Marcel Kaiser Prof. Dr. Bernhard Wünsch Prof. Dr. Thomas J. Schmidt 《ChemMedChem》2020,15(1):68-78
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model. 相似文献
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B. Pantchev P. Danesh K. Antonova B. Schmidt D. Grambole J. Baran 《Journal of Materials Science: Materials in Electronics》2003,14(10-12):751-752
The hydrogen content, its depth distribution, and its bonding configuration have been studied in hydrogenated amorphous silicon prepared by plasma-enhanced chemical vapor deposition with hydrogen-diluted silane. Nuclear reaction analysis and infrared spectroscopy were used to determine the total amount of hydrogen and its bonded component, respectively. It has been established that the total concentration of hydrogen does not depend on the film thickness, and has a uniform depth profile. The concentration of bonded hydrogen changes with the film thickness within the measurement accuracy. The data obtained suggest the presence of molecular (non-bonded) hydrogen, uniformly distributed in concentration across the film thickness. 相似文献
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