TY - GEN A1 - Krüger-Genge, Anne A1 - Jung, Conrad H. G. A1 - Braune, Steffen A1 - Harb, K. A1 - Westphal, S. A1 - Klöpzig, Stefanie A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers T2 - Clinical Hemorheology and Microcirculation N2 - 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. KW - Arthrospira platensis KW - spirulina KW - endothelial cells Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219200 U6 - https://doi.org/10.3233/CH-219200 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 193 EP - 203 ER - TY - GEN A1 - Schulz, Christian A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone T2 - Clinical Hemorheology and Microcirculation N2 - 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. KW - Phase-1 KW - biotransformation KW - CYP KW - cytochrome P450 monooxygenase KW - CYP3A4 KW - diphenyleneiodonium KW - DPI KW - HepG2 KW - HepG2-CYP3A4 KW - hepatocytes KW - NADPH-cytochrome P450 oxidoreductase KW - POR KW - CPR Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219117 U6 - https://doi.org/10.3233/CH-219117 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 231 EP - 243 ER - TY - GEN A1 - Küpper, Jan-Heiner A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - 40th conference of the German society for clinical microcirculation and hemorheology (DGKMH) T2 - Clinical Hemorheology and Microcirculation Y1 - 2021 U6 - https://doi.org/10.3233/ch-219100 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 1 EP - 2 ER - TY - GEN A1 - Jung, Conrad H. G. A1 - Braune, Steffen A1 - Waldeck, Peter A1 - Küpper, Jan-Heiner A1 - Petrick, Ingolf A1 - Jung, Friedrich T1 - Morphology and Growth of Arthrospira platensis during Cultivation in a Flat-Type Bioreactor T2 - Life N2 - 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. KW - Arthrospira platensis KW - Spirulina KW - life cycle KW - morphology KW - fragmentation KW - fission Y1 - 2021 UR - https://www.mdpi.com/2075-1729/11/6/536/htm U6 - https://doi.org/10.3390/life11060536 SN - 2075-1729 VL - 11 IS - 6 ER - TY - GEN A1 - Künzel, Stephan R. A1 - Hoffmann, Maximilian A1 - Weber, Silvio A1 - Künzel, Karolina A1 - Kämmerer, Susanne A1 - Günscht, Mario A1 - Klapproth, Erik A1 - Rausch, Johanna S. E. A1 - Sadek, Mirna S. A1 - Kolanowski, Tomasz A1 - Meyer-Roxlau, Stefanie A1 - Piorkowski, Christopher A1 - Tugtekin, Sems M. A1 - Rose-John, Stefan A1 - Yin, Xiaoke A1 - Mayr, Manuel A1 - Kuhlmann, Jan Dominik A1 - Wimberger, Pauline A1 - Grützmann, Konrad A1 - Herzog, Natalie A1 - Küpper, Jan-Heiner A1 - O’Reilly, Molly A1 - Kabir, S. Nashitha A1 - Sommerfeld, Laura C. A1 - Guan, Kaomei A1 - Wielockx, Ben A1 - Fabritz, Larissa A1 - Nattel, Stanley A1 - Ravens, Ursula A1 - Dobrev, Dobromir A1 - Wagner, Michael A1 - El-Armouche, Ali T1 - Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation T2 - Circulation Research N2 - 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. KW - atrial fibrillation KW - fibroblasts KW - fibrosis KW - mesalamine KW - osteopontin Y1 - 2021 UR - https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.319425 U6 - https://doi.org/10.1161/CIRCRESAHA.121.319425 SN - 1524-4571 SN - 0009-7330 VL - 129 IS - 8 SP - 804 EP - 820 ER - TY - PAT A1 - Scheibner, Katrin A1 - Küpper, Jan-Heiner A1 - Schmidtke, Kai-Uwe A1 - Miethbauer, Sebastian A1 - Herzog, Natalie T1 - Verfahren zur Herstellung von biogenen Stoffen T1 - Method for producing biogenic substances Y1 - 2020 UR - https://patents.google.com/patent/EP3068868B1/de ER - TY - PAT A1 - Scheibner, Katrin A1 - Kiebist, Jan A1 - Schmidtke, Kai-Uwe A1 - Küpper, Jan-Heiner T1 - Verfahren zur enzymatischen Herstellung von zytostatischen 4-Hydroxy-Oxazaphosphorinen“ Y1 - 2020 UR - https://www.b-tu.de/enzymtechnologie/publikationen/patente ER - TY - PAT A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Arthrospira for use in the treatment of diseases Y1 - 2021 UR - https://www.google.de/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwik1t7QrOL5AhVTO-wKHT97CKAQFnoECAQQAQ&url=https%3A%2F%2Fdata.epo.org%2Fpublication-server%2Frest%2Fv1.0%2Fpublication-dates%2F20220302%2Fpatents%2FEP3960193NWA1%2Fdocument.pdf&usg=AOvVaw20GVY_ywjb2xbS0TwSDArJ ER - TY - PAT A1 - Scheibner, Katrin A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - In vitro Arzneimittel aus Prodrugs und deren Verwendung Y1 - 2021 UR - https://www.b-tu.de/enzymtechnologie/publikationen/patente ER - TY - GEN A1 - Vagiannis, Dimitrios A1 - Zhang, Yu A1 - Budagaga, Youssif A1 - Novotna, Eva A1 - Skarka, Adam A1 - Kammerer, Sarah A1 - Küpper, Jan-Heiner A1 - Hofman, Jakub T1 - 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 T2 - Toxicology and Applied Pharmacology Y1 - 2022 U6 - https://doi.org/10.1016/j.taap.2021.115823 SN - 0041-008X VL - Vol. 434 ER -