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71.
Chantal M. Wallenwein Verena Weigel Gtz Hofhaus Namrata Dhakal Wolfgang Schatton Svetlana Gelperina Florian K. Groeber-Becker Jennifer Dressman Matthias G. Wacker 《International journal of molecular sciences》2022,23(24)
Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen–hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies. 相似文献
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Viktoria Constanze Brücher Charlotte Egbring Tanja Plagemann Pavel I. Nedvetsky Verena Hffken Hermann Pavenstdt Nicole Eter Joachim Kremerskothen Peter Heiduschka 《International journal of molecular sciences》2021,22(10)
The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging and functional testing by electroretinography were performed in adult mice. Adult WWC1/2 double knock-out mice differed neither functionally nor morphologically from the control group. In contrast, the retinas of the postnatal WWC knock-out mice showed a hyperproliferative phenotype with significantly enlarged areas of sprouting angiogenesis and a higher number of tip cells. The branching and end points in the peripheral plexus were significantly increased compared to the control group. The deletion of the WWC2 gene was decisive for these effects; while knocking out WWC1 showed no significant differences. The results hint strongly that WWC2 is an essential regulator of ocular angiogenesis in mice. As an activator of the Hippo signalling pathway, it prevents excessive proliferation during physiological angiogenesis. In adult animals, WWC proteins do not seem to be important for the maintenance of the mature vascular plexus. 相似文献
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Dr. Barbara Wienen‐Schmidt Tobias Wulsdorf Dr. Hendrik R. A. Jonker Dr. Krishna Saxena Dr. Denis Kudlinzki Verena Linhard Dr. Sridhar Sreeramulu Prof. Dr. Andreas Heine Prof. Dr. Harald Schwalbe Prof. Dr. Gerhard Klebe 《ChemMedChem》2018,13(18):1988-1996
A ligand‐binding study is presented focusing on thermodynamics of fragment expansion. The binding of four compounds with increasing molecular weight to protein kinase A (PKA) was analyzed. The ligands display affinities between low‐micromolar to nanomolar potency despite their low molecular weight. Binding free energies were measured by isothermal titration calorimetry, revealing a trend toward more entropic and less enthalpic binding with increase in molecular weight. All protein–ligand complexes were analyzed by crystallography and solution NMR spectroscopy. Crystal structures and solution NMR data are highly consistent, and no major differences in complex dynamics across the series are observed that would explain the differences in the thermodynamic profiles. Instead, the thermodynamic trends result either from differences in the solvation patterns of the conformationally more flexible ligand in aqueous solution prior to protein binding as molecular dynamics simulations suggest, or from local shifts of the water structure in the ligand‐bound state. Our data thus provide evidence that changes in the solvation pattern constitute an important parameter for the understanding of thermodynamic data in protein–ligand complex formation. 相似文献
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Verena Schochlow Stephan Neumann Kristoffer Braun Melanie Volkamer 《Datenschutz und Datensicherheit - DuD》2016,40(5):295-299
Ende-zu-Ende-verschlüsselte E-Mail-Kommunikation hat seit den Veröffentlichungen von Edward Snowden erneut an Bedeutung gewonnen. Obwohl die entsprechenden Möglichkeiten seit mehr als zwei Jahrzehnten gegeben sind, sind die technischen Umsetzungen für Endanwender häufig schwer zugänglich. Ein wesentlicher Grund dafür ist, wie Studien belegen, deren Nutzerschnittstelle. Mit Mailvelope versuchen die Anbieter GMX und WEB.DE derzeit, Ende-zu-Ende-verschlüsselte E-Mail-Kommunikation in ihren gewohnten Benutzerschnittstellen zu integrieren. Zur Bewertung dieses Ansatzes wurden ein Cognitive Walkthrough durchgeführt und die Sicherheit des Ansatzes bewertet. 相似文献
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Linar Mikeev Martin R. Neuhäußer David Spieler Verena Wolf 《Formal Methods in System Design》2013,43(2):313-337
We consider continuous-time Markov chains (CTMC) with very large or infinite state spaces which are, for instance, used to model biological processes or to evaluate the performance of computer and communication networks. We propose a numerical integration algorithm to approximate the probability that a process conforms to a specification that belongs to a subclass of deterministic timed automata (DTAs). We combat the state space explosion problem by using a dynamic state space that contains only the most relevant states. In this way we avoid an explicit construction of the state-transition graph of the composition of the DTA and the CTMC. We also show how to maximize the probability of acceptance of the DTA for parametric CTMCs and substantiate the usefulness of our approach with experimental results from biological case studies. 相似文献