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排序方式: 共有302条查询结果,搜索用时 15 毫秒
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Nadine Kretschmer Antje Hufner Christin Durchschein Katrin Popodi Beate Rinner Birgit Lohberger Rudolf Bauer 《International journal of molecular sciences》2021,22(5)
Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma. 相似文献
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Bernhard Kienesberger Beate Obermüller Georg Singer Barbara Mittl Reingard Grabherr Sigrid Mayrhofer Stefan Heinl Vanessa Stadlbauer Angela Horvath Wolfram Miekisch Patricia Fuchs Ingeborg Klymiuk Holger Till Christoph Castellani 《International journal of molecular sciences》2021,22(12)
We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile. 相似文献
4.
Horst Kesselmeier Inga Tschiersch Klaus Henning Beate Stoffels Sebastian Kutscha 《AI & Society》1998,12(1-2):55-63
Today technology design can no longer be understood as a design process on a green site. Design and implementation of new technology are always dependent on existing technology and the way it is used by people. In this respect Software-Engineering has also changed to the characteristics of normal technology design taking into account existing computer systems. Experiences show that the conditions and needs of such Software-Reengineering projects are highly complex and differ in their special characteristics ranging from aspects of quality of existing system documentation to organizational structures of the computer departments concerned. The Task-Artifact Cycle presented here gives a suitable reengineering approach emphasizing both analysis and design in Software-Reengineering. 相似文献
5.
Beate Grawemeyer 《Interacting with computers》2011,23(3):256-267
Security policies are required that protect information from unauthorised access, and also respect challenges users face in creating, and particularly managing, increasing numbers of passwords. This paper investigates real password use in the context of daily life. It presents the results of an empirical study where participants completed a password diary over 7 days, followed by debrief interviews to gain further knowledge and understanding of user behaviour. The results reported relate to how many passwords are in use, the types of passwords participants created, the relationships between different passwords and to sensitive services, how participants retrieved their passwords and finally, the different strategies adopted by users in their management of passwords. The paper concludes by providing a high level set of password guidelines, along with suggestions for mechanisms to support creating, encoding, retrieving and executing multiple passwords. 相似文献
6.
Yanka Jeliazova Michael Kayser Beate Mildner Achim Walter Hassel Detlef Diesing 《Thin solid films》2006,500(1-2):330-335
The dielectric breakdown of thin (d = 3–4 nm) aluminium and tantalum oxide films was investigated by means of current voltage plots in metal/insulator/metal systems. Dielectric breakdown field strengths, EDB, of 0.6 GV m− 1 were found for both oxide types at room temperature. Differences appear in the temperature dependence of EDB. Tantalum oxide films show an unchanged breakdown behaviour for temperatures up to 420 K while aluminium oxide films lose already 80% of their EDB value in the same temperature range. Time-resolved investigations of the electric breakdown revealed intermediate states of both oxide types which were stable for several ms being characterized by an enhanced tunnel current. The breakdown voltage clearly scales with the oxide thickness for both oxide types. 相似文献
7.
Nadine Kretschmer Christin Durchschein Antje Hufner Beate Rinner Birgit Lohberger Rudolf Bauer 《International journal of molecular sciences》2022,23(10)
Melanoma is a complex and heterogenous disease, displays the deadliest form of skin cancer, and accounts for approx. 80% of all skin cancer deaths. In this study, we reported on the synthesis and pharmacological effects of a novel shikonin derivative (SK119), which is active in a nano-molar range and exhibits several promising in vitro effects in different human melanoma cells. SK119 was synthesized from shikonin as part of our search for novel, promising shikonin derivatives. It was screened against a panel of melanoma and non-tumorigenic cell lines using XTT viability assays. Moreover, we studied its pharmacological effects using apoptosis and Western blot experiments. Finally, it was combined with current clinically used melanoma therapeutics. SK119 exhibited IC50 values in a nano-molar range, induced apoptosis and led to a dose-dependent increase in the expression and protein phosphorylation of HSP27 and HSP90 in WM9 and MUG-Mel 2 cells. Combinatorial treatment, which is highly recommended in melanoma, revealed the synergistic effects of SK119 with vemurafenib and cobimetinib. SK119 treatment changed the expression levels of apoptosis genes and death receptor expression and exhibited synergistic effects with vemurafenib and cobimetinib in human melanoma cells. Further research indicates a promising potential in melanoma therapy. 相似文献
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Maria José Farré Sophie Day Peta A. Neale Daniel Stalter Janet Y.M. Tang Beate I. Escher 《Water research》2013
Disinfection by-products (DBP) formed from natural organic matter and disinfectants like chlorine and chloramine may cause adverse health effects. Here, we evaluate how the quantity and quality of natural organic matter and other precursors influence the formation of DBPs during chlorination and chloramination using a comprehensive approach including chemical analysis of regulated and emerging DBPs, total organic halogen quantification, organic matter characterisation and bioanalytical tools. In vitro bioassays allow us to assess the hazard potential of DBPs early in the chain of cellular events, when the DBPs react with their molecular target(s) and activate stress response and defence mechanisms. Given the reactive properties of known DBPs, a suite of bioassays targeting reactive modes of toxic action including genotoxicity and sensitive early warning endpoints such as protein damage and oxidative stress were evaluated in addition to cytotoxicity. Coagulated surface water was collected from three different drinking water treatment plants, along with reverse osmosis permeate from a desalination plant, and DBP formation potential was assessed after chlorination and chloramination. While effects were low or below the limit of detection before disinfection, the observed effects and DBP levels increased after disinfection and were generally higher after chlorination than after chloramination, indicating that chlorination forms higher concentrations of DBPs or more potent DBPs in the studied waters. Bacterial cytotoxicity, assessed using the bioluminescence inhibition assay, and induction of the oxidative stress response were the most sensitive endpoints, followed by genotoxicity. Source waters with higher dissolved organic carbon levels induced increased DBP formation and caused greater effects in the endpoints related to DNA damage repair, glutathione conjugation/protein damage and the Nrf2 oxidative stress response pathway after disinfection. Fractionation studies indicated that all molecular weight fractions of organic carbon contributed to the DBP formation potential, with the humic rich fractions forming the greatest amount of DBPs, while the low molecular weight fractions formed more brominated DBPs due to the high bromide to organic carbon ratio. The presence of higher bromide concentrations also led to a higher fraction of brominated DBPs as well as proportionally higher effects. This study demonstrates how a suite of analytical and bioanalytical tools can be used to effectively characterise the precursors and formation potential of DBPs. 相似文献