@misc{KruegerGengeJungBrauneetal., author = {Kr{\"u}ger-Genge, Anne and Jung, Conrad H. G. and Braune, Steffen and Harb, K. and Westphal, S. and Kl{\"o}pzig, Stefanie and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers}, series = {Clinical Hemorheology and Microcirculation}, volume = {79}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-219200}, pages = {193 -- 203}, abstract = {Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109\%. Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.}, language = {en} } @misc{SchulzJungKuepper, author = {Schulz, Christian and Jung, Friedrich and K{\"u}pper, Jan-Heiner}, title = {Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone}, series = {Clinical Hemorheology and Microcirculation}, volume = {79}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-219117}, pages = {231 -- 243}, abstract = {Cell-based in vitro liver models are an important tool in the development and evaluation of new drugs in pharmacological and toxicological drug assessment. Hepatic microsomal enzyme complexes, consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs), play a decisive role in catalysing phase-1 biotransformation of pharmaceuticals and xenobiotics. For a comprehensive understanding of the phase-1 biotransformation of drugs, the availability of well-characterized substances for the targeted modulation of in vitro liver models is essential. In this study, we investigated diphenyleneiodonium (DPI) for its ability to inhibit phase-1 enzyme activity and further its toxicological profile in an in vitro HepG2 cell model with and without recombinant expression of the most important drug metabolization enzyme CYP3A4. Aim of the study was to identify effective DPI concentrations for CPR/CYP activity modulation and potentially associated dose and time dependent hepatotoxic effects. The cells were treated with DPI doses up to 5,000nM (versus vehicle control) for a maximum of 48 h and subsequently examined for CYP3A4 activity as well as various toxicological relevant parameters such as cell morphology, integrity and viability, intracellular ATP level, and proliferation. Concluding, the experiments revealed a time- and concentration-dependent DPI mediated partial and complete inhibition of CYP3A4 activity in CYP3A4 overexpressing HepG2-cells (HepG2-CYP3A4). Other cell functions, including ATP synthesis and consequently the proliferation were negatively affected in both in vitro cell models. Since neither cell integrity nor cell viability were reduced, the effect of DPI in HepG2 can be assessed as cytostatic rather than cytotoxic.}, language = {en} } @misc{KuepperKruegerGengeJung, author = {K{\"u}pper, Jan-Heiner and Kr{\"u}ger-Genge, Anne and Jung, Friedrich}, title = {40th conference of the German society for clinical microcirculation and hemorheology (DGKMH)}, series = {Clinical Hemorheology and Microcirculation}, volume = {79}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/ch-219100}, pages = {1 -- 2}, language = {en} } @misc{JungBrauneWaldecketal., author = {Jung, Conrad H. G. and Braune, Steffen and Waldeck, Peter and K{\"u}pper, Jan-Heiner and Petrick, Ingolf and Jung, Friedrich}, title = {Morphology and Growth of Arthrospira platensis during Cultivation in a Flat-Type Bioreactor}, series = {Life}, volume = {11}, journal = {Life}, number = {6}, issn = {2075-1729}, doi = {10.3390/life11060536}, abstract = {Arthrospira platensis (AP) is a cyanobacterium with a high economic value and is nowadays one of the most important industrially cultivated microalgae. Knowledge of its growth is essential for the understanding of its physiology and yield. The growth of AP biomass occurs through two mechanisms: (1) propagation by fragmentation of trichomes, and (2) the trichomes are extended by binary fission until they reach their mature status. These phases are visualized by live cell light and laser scanning microscopy, demonstrating the different phases of AP growth.}, language = {en} } @misc{KuenzelHoffmannWeberetal., author = {K{\"u}nzel, Stephan R. and Hoffmann, Maximilian and Weber, Silvio and K{\"u}nzel, Karolina and K{\"a}mmerer, Susanne and G{\"u}nscht, Mario and Klapproth, Erik and Rausch, Johanna S. E. and Sadek, Mirna S. and Kolanowski, Tomasz and Meyer-Roxlau, Stefanie and Piorkowski, Christopher and Tugtekin, Sems M. and Rose-John, Stefan and Yin, Xiaoke and Mayr, Manuel and Kuhlmann, Jan Dominik and Wimberger, Pauline and Gr{\"u}tzmann, Konrad and Herzog, Natalie and K{\"u}pper, Jan-Heiner and O'Reilly, Molly and Kabir, S. Nashitha and Sommerfeld, Laura C. and Guan, Kaomei and Wielockx, Ben and Fabritz, Larissa and Nattel, Stanley and Ravens, Ursula and Dobrev, Dobromir and Wagner, Michael and El-Armouche, Ali}, title = {Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation}, series = {Circulation Research}, volume = {129}, journal = {Circulation Research}, number = {8}, issn = {1524-4571}, doi = {10.1161/CIRCRESAHA.121.319425}, pages = {804 -- 820}, abstract = {Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between PLK2 (polo-like kinase 2) and the profibrotic cytokine OPN (osteopontin) in the pathogenesis of atrial fibrosis and AF. Methods and Results: Atrial PLK2 mRNA expression was 10-fold higher in human fibroblasts than in cardiomyocytes. Compared with sinus rhythm, right atrial appendages and isolated right atrial fibroblasts from patients with AF showed downregulation of PLK2 mRNA and protein, along with increased PLK2 promotor methylation. Genetic deletion as well as pharmacological inhibition of PLK2 induced profibrotic phenotype conversion in cardiac fibroblasts and led to a striking de novo secretion of OPN. Accordingly, PLK2-deficient (PLK2 knockout) mice showed cardiac fibrosis and were prone to experimentally induced AF. In line with these findings, OPN plasma levels were significantly higher only in patients with AF with atrial low-voltage zones (surrogates of fibrosis) compared with sinus rhythm controls. Mechanistically, we identified ERK1/2 as the relevant downstream mediator of PLK2 leading to increased OPN expression. Finally, oral treatment with the clinically available drug mesalazine, known to inhibit ERK1/2, prevented cardiac OPN overexpression and reversed the pathological PLK2 knockout phenotype in PLK2 knockout mice. Conclusions: Abnormal PLK2/ERK1/2/OPN axis function critically contributes to AF-related atrial fibrosis, suggesting reinforcing PLK2 activity and/or OPN inhibition as innovative targets to prevent fibrosis progression in AF. Mesalazine derivatives may be used as lead compounds for the development of novel anti-AF agents targeting fibrosis.}, language = {en} } @misc{ScheibnerKuepperSchmidtkeetal., author = {Scheibner, Katrin and K{\"u}pper, Jan-Heiner and Schmidtke, Kai-Uwe and Miethbauer, Sebastian and Herzog, Natalie}, title = {Verfahren zur Herstellung von biogenen Stoffen}, language = {de} } @misc{ScheibnerKiebistSchmidtkeetal., author = {Scheibner, Katrin and Kiebist, Jan and Schmidtke, Kai-Uwe and K{\"u}pper, Jan-Heiner}, title = {Verfahren zur enzymatischen Herstellung von zytostatischen 4-Hydroxy-Oxazaphosphorinen"}, language = {de} } @misc{KuepperJung, author = {K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Arthrospira for use in the treatment of diseases}, pages = {13}, language = {en} } @misc{ScheibnerKuepperJung, author = {Scheibner, Katrin and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {In vitro Arzneimittel aus Prodrugs und deren Verwendung}, language = {de} } @misc{VagiannisZhangBudagagaetal., author = {Vagiannis, Dimitrios and Zhang, Yu and Budagaga, Youssif and Novotna, Eva and Skarka, Adam and Kammerer, Sarah and K{\"u}pper, Jan-Heiner and Hofman, Jakub}, title = {Alisertib shows negligible potential for perpetrating pharmacokinetic drug-drug interactions on ABCB1, ABCG2 and cytochromes P450, but acts as dual-activity resistance modulator through the inhibition of ABCC1 transporter}, series = {Toxicology and Applied Pharmacology}, volume = {Vol. 434}, journal = {Toxicology and Applied Pharmacology}, issn = {0041-008X}, doi = {10.1016/j.taap.2021.115823}, pages = {13}, language = {en} }