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排序方式: 共有321条查询结果,搜索用时 11 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
3.
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.
Daniel Alexander Bizjak Lucas John Lynn Matits Alisa Uhl Sebastian Victor Waldemar Schulz Jana Schellenberg Johannes Peifer Wilhelm Bloch Manfred Weiß Beate Grüner Hendrik Bracht Jürgen Michael Steinacker Marijke Grau 《International journal of molecular sciences》2022,23(23)
Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0–T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients. 相似文献
8.
9.
Claudia Pielsticker Martin F. Brodde Lisa Raum Kerstin Jurk Beate E. Kehrel 《International journal of molecular sciences》2020,21(22)
Inflammatory processes are triggered by the fibrinolytic enzyme plasmin. Tissue-type plasminogen activator, which cleaves plasminogen to plasmin, can be activated by the cross-β-structure of misfolded proteins. Misfolded protein aggregates also represent substrates for plasmin, promoting their degradation, and are potent platelet agonists. However, the regulation of plasmin-mediated platelet activation by misfolded proteins and vice versa is incompletely understood. In this study, we hypothesize that plasmin acts as potent agonist of human platelets in vitro after short-term incubation at room temperature, and that the response to thrombospondin-1 and the bona fide misfolded proteins Eap and SCN−-denatured IgG interfere with plasmin, thereby modulating platelet activation. Plasmin dose-dependently induced CD62P surface expression on, and binding of fibrinogen to, human platelets in the absence/presence of plasma and in citrated whole blood, as analyzed by flow cytometry. Thrombospondin-1 pre-incubated with plasmin enhanced these plasmin-induced platelet responses at low concentration and diminished them at higher dose. Platelet fibrinogen binding was dose-dependently induced by the C-terminal thrombospondin-1 peptide RFYVVMWK, Eap or NaSCN-treated IgG, but diminished in the presence of plasmin. Blocking enzymatically catalyzed thiol-isomerization decreased plasmin-induced platelet responses, suggesting that plasmin activates platelets in a thiol-dependent manner. Thrombospondin-1, depending on the concentration, may act as cofactor or inhibitor of plasmin-induced platelet activation, and plasmin blocks platelet activation induced by misfolded proteins and vice versa, which might be of clinical relevance. 相似文献
10.
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