@misc{HerzogHansenMiethbaueretal., author = {Herzog, Natalie and Hansen, Max and Miethbauer, Sebastian and Schmidtke, Kai-Uwe and Anderer, Ursula and Lupp, Amelie and Sperling, Sebastian and Seehofer, Daniel and Damm, Georg and Scheibner, Katrin and K{\"u}pper, Jan-Heiner}, title = {Primary-like human hepatocytes genetically engineered to obtain proliferation competence display hepatic differentiation characteristics in monolayer and organotypical spheroid cultures}, series = {Cell Biology International}, volume = {40}, journal = {Cell Biology International}, number = {3}, issn = {1095-8355}, doi = {10.1002/cbin.10574}, pages = {341 -- 353}, abstract = {Primary human hepatocytes are in great demand during drug development and in hepatology. However, both scarcity of tissue supply and donor variability of primary cells create a need for the development of alternative hepatocyte systems. By using a lentivirus vector system to transfer coding sequences of Upcyte® proliferation genes, we generated non-transformed stable hepatocyte cultures from human liver tissue samples. Here, we show data on newly generated proliferation-competent HepaFH3 cells investigated as conventional two-dimensional monolayer and as organotypical three-dimensional (3D) spheroid culture. In monolayer culture, HepaFH3 cells show typical cobblestone-like hepatocyte morphology and anchorage-dependent growth for at least 20 passages. Immunofluorescence staining revealed that characteristic hepatocyte marker proteins cytokeratin 8, human serum albumin, and cytochrome P450 (CYP) 3A4 were expressed. Quantitative real-time PCR analyses showed that expression levels of analyzed phase I CYP enzymes were at similar levels compared to those of cultured primary human hepatocytes and considerably higher than in the liver carcinoma cell line HepG2. Additionally, transcripts for phase II liver enzymes and transporter proteins OATP-C, MRP2, Oct1, and BSEP were present in HepaFH3. The cells produced urea and converted model compounds such as testosterone, diclofenac, and 7-OH-coumarin into phases I and II metabolites. Interestingly, phases I and II enzymes were expressed at about the same levels in convenient monolayer cultures and complex 3D spheroids. In conclusion, HepaFH3 cells and related primary-like hepatocyte lines seem to be promising tools for in vitro research of liver functions and as test system in drug development and toxicology analysis.}, language = {en} } @misc{KadeHerzogSchmidtkeetal., author = {Kade, S. and Herzog, Natalie and Schmidtke, Kai-Uwe and K{\"u}pper, Jan-Heiner}, title = {Chronic ethanol treatment depletes glutathione regeneration capacity in hepatoma cell line HepG2}, series = {Journal of Cellular Biotechnology}, volume = {1}, journal = {Journal of Cellular Biotechnology}, number = {2}, issn = {2352-3697}, doi = {10.3233/JCB-15019}, pages = {183 -- 190}, language = {en} } @misc{HerzogHansenMiethbaueretal., author = {Herzog, Natalie and Hansen, Max and Miethbauer, Sebastian and Schmidtke, Kai-Uwe and Anderer, Ursula and Lupp, Amelie and Sperling, Sebastian and Seehofer, Daniel and Damm, Georg and Scheibner, Katrin and K{\"u}pper, Jan-Heiner}, title = {Primary like human hepatocytes genetically engineered to obtain proliferation competence display liver biotransformation activity in 2D and 3D culture systems}, series = {Cell Biology International}, volume = {40}, journal = {Cell Biology International}, number = {3}, issn = {1095-8355}, pages = {341 -- 353}, language = {en} } @misc{GeorgeRoedigerSchroederetal., author = {George, Sandra and R{\"o}diger, Stefan and Schr{\"o}der, Christian and Knaut, Michael and K{\"u}pper, Jan-Heiner}, title = {Development of multiplex PCR systems for expression profiling of human cardiomyocytes induced to profilerate by lentivirus transduction of upcyte genes}, series = {Journal of Cellular Biotechnology}, volume = {2}, journal = {Journal of Cellular Biotechnology}, number = {1}, issn = {2352-3697}, doi = {10.3233/JCB-15025}, pages = {35 -- 55}, language = {en} } @misc{MeyerMeyerFiccaKuepper, author = {Meyer, Ralph G. and Meyer-Ficca, Mirella and K{\"u}pper, Jan-Heiner}, title = {Adenoviral vectors for modulation of poly(ADP-ribose) polymerase-1 (PARP1) - dependent DNA repair as a predictive tool for chemotherapy}, series = {Journal of Cellular Biotechnology}, volume = {2}, journal = {Journal of Cellular Biotechnology}, number = {1}, issn = {2352-3697}, doi = {10.3233/JCB-15026}, pages = {57 -- 68}, language = {en} } @misc{HerzogKatzenbergerMartinetal., author = {Herzog, Natalie and Katzenberger, Nadine and Martin, Frank and Schmidtke, Kai-Uwe and K{\"u}pper, Jan-Heiner}, title = {Generation of cytochrome P450 3A4-overexpressing HepG2 cell clones for standardization of hepatocellular testosterone 6β-hydroxylation activity}, series = {Journal of Cellular Biotechnology}, volume = {1}, journal = {Journal of Cellular Biotechnology}, number = {1}, issn = {2352-3697}, doi = {10.3233/JCB-15002}, pages = {15 -- 26}, language = {en} } @misc{GeorgeNoackVaneketal., author = {George, Sandra and Noack, M. and Vanek, Monika and Rentzsch, J. and R{\"o}ber, Nadja and Roggenbuck, Dirk and Conrad, Karsten and K{\"u}pper, Jan-Heiner}, title = {Expression of nicotinic acetylcholine receptor subunits in HEp-2 cells for immunodetection of autoantibody specificities in sera fro Myasthenia gravis patients}, series = {Clinical Hemorheology and Microcirculation}, volume = {61}, journal = {Clinical Hemorheology and Microcirculation}, number = {2}, issn = {1875-8622}, doi = {10.3233/CH-151999}, pages = {385 -- 396}, language = {en} } @misc{GeorgePaulickKnuetteretal., author = {George, Sandra and Paulick, Silvia and Kn{\"u}tter, Ilka and R{\"o}ber, Nadja and Hiemann, Rico and Roggenbuck, Dirk and Conrad, Karsten and K{\"u}pper, Jan-Heiner}, title = {Stable Expression of Human Muscle-Specific Kinase in HEp-2 M4 Cells for Automatic Immunofluorescence Diagnostics of Myasthenia Gravis}, series = {PLOS one}, volume = {9}, journal = {PLOS one}, number = {1}, issn = {1932-6203}, doi = {10.1371/journal.pone.0083924}, pages = {e83924}, language = {en} } @misc{GeorgeGeorgiRoggenbucketal., author = {George, Sandra and Georgi, M. and Roggenbuck, Dirk and Conrad, Karsten and K{\"u}pper, Jan-Heiner}, title = {A strategy for cell-based multiplex diagnostics of Myasthenia gravis and autoimmune encephalitis by modifying the subcellular localization of cell membrane autoantigensgravis}, series = {Clinical Hemorheology and Microcirculation}, volume = {58}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1386-0291}, doi = {10.3233/CH-141897}, pages = {211 -- 228}, language = {en} } @incollection{ConradKuepper, author = {Conrad, Karsten and K{\"u}pper, Jan-Heiner}, title = {Tumor-associated autoantibodies}, series = {Autoantibodies}, booktitle = {Autoantibodies}, editor = {Shoenfeld, Yehuda and Meroni, Pier Luigi and Gershwin, M. Eric}, edition = {3rd edition}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, isbn = {978-0-444-56378-1}, pages = {275 -- 287}, language = {en} } @misc{NowakMartinGeorgeetal., author = {Nowak, Elisabeth and Martin, F. and George, Sandra and R{\"o}ber, Nadja and Conrad, Karsten and K{\"u}pper, Jan-Heiner}, title = {Bacterial production and purification of immunoreactive paraneoplastic neurological syndrome autoantigen Ma2}, series = {Journal of Cellular Biotechnology}, volume = {2}, journal = {Journal of Cellular Biotechnology}, number = {2}, issn = {2352-3697}, doi = {10.3233/JCB-15029}, pages = {85 -- 91}, abstract = {Paraneoplastic neurological syndromes (PNS) are caused by an immune response against neuronal proteins upon their ectopical expression in tumor cells. Ma2 belongs to the protein family of paraneoplastic Ma antigens (PNMA). Detection of Ma2-specific autoantibodies is relevant for diagnostics of anti-Ma2 PNS and an underlying tumor such as germ testicular cancer, small cell lung cancer or breast cancer. Thus, early tumor treatment should improve the outcome for PNS therapy either. Dot blot immunoassay based on recombinantly expressed and purified autoantigens could offer a sensitive method for identification of paraneoplastic autoantibodies from sera of PNS patients. Here we present purification with IMAC and FPLC of human Ma2 autoantigen upon its recombinant expression in E.coli. Furthermore, we provide evidence that dot blot immunoassays with purified Ma2 autoantigen can be used for detection of Ma2-specific autoantibodies from sera of PNS patients.}, language = {en} } @book{PaumenKuepper, author = {Paumen, Anja and K{\"u}pper, Jan-Heiner}, title = {It's the planet, stupid! Sieben Perspektiven zum Klimawandel : mit Interviewbeitr{\"a}gen von Hartmut Graßl, Hans-Werner Sinn, Ernst-Ulrich von Weizs{\"a}cker, Meinhard Miegel, Mathias Binswanger, Enoch zu Guttenberg und Wulf Schiefenh{\"o}vel}, publisher = {oekom Verlag}, address = {M{\"u}nchen}, isbn = {978-3-86581-739-6}, pages = {303}, language = {de} } @inproceedings{GeorgeNoackVaneketal., author = {George, Sandra and Noack, Monika and Vanek, Monika and Rentzsch, Juliane and R{\"o}ber, Nadja and Conrad, Karsten and Roggenbuck, Dirk and K{\"u}pper, Jan-Heiner}, title = {Expression of nicotinic acetylcholine receptor subunits in HEp-2 cells for immunodetection of autoantibody specificities in sera from Myasthenia gravis patients}, series = {From autoantibody research to standardized diagnostic assays in the management of human diseases, report on the 12th Dresden Symposium on Autoantibodies, September 23-26, 2015}, booktitle = {From autoantibody research to standardized diagnostic assays in the management of human diseases, report on the 12th Dresden Symposium on Autoantibodies, September 23-26, 2015}, publisher = {Pabst Science Publishers}, address = {Lengerich}, isbn = {978-3-95853-104-8}, pages = {195 -- 196}, language = {en} } @misc{KammererKuepper, author = {Kammerer, Sarah and K{\"u}pper, Jan-Heiner}, title = {Human Hepatocyte Systems for in vitro Toxicology Analysis.}, series = {Journal of Cellular Biotechnology}, volume = {3}, journal = {Journal of Cellular Biotechnology}, number = {2}, issn = {2352-3697}, doi = {10.3233/JCB-179012}, pages = {85 -- 93}, language = {en} } @misc{HailekaGeorgeSteinbrechtetal., author = {Haileka, Vanessa and George, Sandra and Steinbrecht, Susanne and Jung, Friedrich and Reinehr, R. and K{\"u}pper, Jan-Heiner}, title = {Colon cancer cells cultured under hyperosmotic conditions as in vitro model to investigate dehydration effects on cancer drug susceptibility}, series = {Clinical Hemorheology and Microcirculation}, volume = {73}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-199210}, pages = {169 -- 176}, language = {en} } @misc{SchulteHubbertKuepperThomasetal., author = {Schulte-Hubbert, Ruth and K{\"u}pper, Jan-Heiner and Thomas, Adam D. and Schrenk, Dieter}, title = {Estragole: DNA adduct formation in primary rat hepatocytes and genotoxic potential in HepG2-CYP1A2 cells}, series = {Toxicology}, volume = {444}, journal = {Toxicology}, issn = {0300-483X}, doi = {10.1016/j.tox.2020.152566}, pages = {8}, abstract = {Estragole is a natural constituent in herbs and spices and in products thereof such as essential oils or herbal teas. After cytochrome P450-catalyzed hydroxylation and subsequent sulfation, estragole acts as a genotoxic hepatocarcinogen forming DNA adducts in rodent liver. Because of the genotoxic mode of action and the widespread occurrence in food and phytomedicines a refined risk assessment for estragole is needed. We analyzed the time- and concentration-dependent levels of the DNA adducts N2-(isoestragole-3'-yl)-2'-desoxyguanosine (E3′N2dG) and N6-(isoestragole-3'-yl)-desoxyadenosine (E3′N6dA), reported to be the major adducts formed in rat liver, in rat hepatocytes (pRH) in primary culture after incubation with estragole. DNA adduct levels were measured via UHPLC-ESI-MS/MS using stable isotope dilution analysis. Both adducts were formed in pRH and could already be quantified after an incubation time of 1 h (E3′N6dA at 10 μM, E3′N2dG at 1μM estragole). E3′N2dG, the main adduct at all incubation times and concentrations, could be detected at estragole concentrations < 0.1 μM after 24 h and < 0.5 μM after 48 h. Adduct levels were highest after 6 h and showed a downward trend at later time-points, possibly due to DNA repair and/or apoptosis. While the concentration-response characteristics of adduct formation were apparently linear over the whole concentration range, strong indication for marked hypo-linearity was obtained when the modeling was based on concentrations < 1 μM only. In the micronucleus assay no mutagenic potential of estragole was found in HepG2 cells whereas in HepG2-CYP1A2 cells 1 μM estragole led to a 3.2 fold and 300 μM to a 7.1 fold increase in micronuclei counts. Our findings suggest the existence of a 'practical threshold' dose for DNA adduct formation as an initiating key event of the carcinogenicity of estragole indicating that the default assumption of concentration-response-linearity is questionable, at least for the two major adducts studied here.}, language = {en} } @misc{RutzGaoKuepperetal., author = {Rutz, Lukas and Gao, Lan and K{\"u}pper, Jan-Heiner and Schrenk, Dieter}, title = {Structure-dependent genotoxic potencies of selected pyrrolizidine alkaloids in metabolically competent HepG2 cells}, series = {Archives of Toxicology}, volume = {94}, journal = {Archives of Toxicology}, number = {12}, issn = {0340-5761}, doi = {10.1007/s00204-020-02895-z}, pages = {4159 -- 4172}, abstract = {1,2-unsaturated pyrrolizidine alkaloids (PAs) are natural plant constituents comprising more than 600 different structures. A major source of human exposure is thought to be cross-contamination of food, feed and phytomedicines with PA plants. In humans, laboratory and farm animals, certain PAs exert pronounced liver toxicity and can induce malignant liver tumors in rodents. Here, we investigated the cytotoxicity and genotoxicity of eleven PAs belonging to different structural classes. Although all PAs were negative in the fluctuation Ames test in Salmonella, they were cytotoxic and induced micronuclei in human HepG2 hepatoblastoma cells over-expressing human cytochrome P450 3A4. Lasiocarpine and cyclic diesters except monocrotaline were the most potent congeners both in cytotoxicity and micronucleus assays with concentrations below 3 μM inducing a doubling in micronuclei counts. Other open di-esters and all monoesters exhibited weaker or much weaker geno- and cytotoxicity. The findings were in agreement with recently suggested interim Relative Potency (iREP) factors with the exceptions of europine and monocrotaline. A more detailed micronuclei analysis at low concentrations of lasiocarpine, retrorsine or senecionine indicated that pronounced hypolinearity of the concentration-response curves was evident for retrorsine and senecionine but not for lasiocarpine. Our findings show that the genotoxic and cytotoxic potencies of PAs in a human hepatic cell line vary in a structure-dependent manner. Both the low potency of monoesters and the shape of prototype concentration-response relationships warrant a substance- and structure-specific approach in the risk assessment of PAs.}, language = {en} } @misc{KuenzelRauschSchaefferetal., author = {K{\"u}nzel, Stephan R. and Rausch, Johanna S. E. and Sch{\"a}ffer, Charlotte and Hoffmann, Maximilian and K{\"u}nzel, Karolina and Klapproth, Erik and Kant, Theresa and Herzog, Natalie and K{\"u}pper, Jan-Heiner and Lorenz, Kristina and Dudek, Svenja and Emig, Ramona and Ravens, Ursula and Rog-Zielinska, Eva A. and Peyronnet, R{\´e}mi and El-Armouche, Ali}, title = {Modeling atrial fibrosis in vitro - Generation and characterization of a novel human atrial fibroblast cell line}, series = {FEBS Open Bio}, volume = {10}, journal = {FEBS Open Bio}, number = {7}, issn = {2211-5463}, doi = {10.1002/2211-5463.12896}, pages = {1210 -- 1218}, abstract = {Atrial fibrillation (AF) is regularly accompanied by cardiac fibrosis and concomitant heart failure. Due to the heterogeneous nature and complexity of fibrosis, the knowledge about the underlying mechanisms is limited, which prevents effective pharmacotherapy. A deeper understanding of cardiac fibroblasts is essential to meet this need. We previously described phenotypic and functional differences between atrial fibroblasts from patients in sinus rhythm and with AF. Herein, we established and characterized a novel human atrial fibroblast line, which displays typical fibroblast morphology and function comparable to primary cells but with improved proliferation capacity and low spontaneous myofibroblast differentiation. These traits make our model suitable for the study of fibrosis mechanisms and for drug screening aimed at developing effective antifibrotic pharmacotherapy.}, language = {en} } @misc{JungKruegerGengeFrankeetal., author = {Jung, Friedrich and Kr{\"u}ger-Genge, Anne and Franke, Ralf-Peter and Hufert, Frank and K{\"u}pper, Jan-Heiner}, title = {COVID-19 and the endothelium}, series = {Clinical Hemorheology and Microcirculation}, volume = {75}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-209007}, pages = {7 -- 11}, abstract = {There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. Recent studies showed that this can lead to microcirculatory impairments and in consequence to functional disorders of all inner organs. The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions.}, language = {en} } @misc{JungKriegerHufertetal., author = {Jung, Friedrich and Krieger, Volker and Hufert, Frank and K{\"u}pper, Jan-Heiner}, title = {Herd immunity or suppression strategy to combat COVID-19}, series = {Clinical Hemorheology and Microcirculation}, volume = {75}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-209006}, pages = {13 -- 17}, abstract = {Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called "herd immunity" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden. Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants).}, language = {en} } @misc{SteinbrechtKiebistKoenigetal., author = {Steinbrecht, Susanne and Kiebist, Jan and K{\"o}nig, Rosalie and Thiessen, Markus and Schmidtke, Kai-Uwe and Kammerer, Sarah and K{\"u}pper, Jan-Heiner and Scheibner, Katrin}, title = {Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius rotula for toxicological studies on human cancer cells}, series = {AMB Express}, volume = {10}, journal = {AMB Express}, issn = {2191-0855}, doi = {10.1186/s13568-020-01064-w}, pages = {13}, abstract = {Cyclophosphamide (CPA) represents a widely used anti-cancer prodrug that is converted by liver cytochrome P450 (CYP) enzymes into the primary metabolite 4-hydroxycyclophosphamide (4-OH-CPA), followed by non-enzymatic generation of the bioactive metabolites phosphoramide mustard and acrolein. The use of human drug metabolites as authentic standards to evaluate their toxicity is essential for drug development. However, the chemical synthesis of 4-OH-CPA is complex and leads to only low yields and undesired side products. In past years, fungal unspecific peroxygenases (UPOs) have raised to powerful biocatalysts. They can exert the identical selective oxyfunctionalization of organic compounds and drugs as known for CYP enzymes with hydrogen peroxide being used as sole cosubstrate. Herein, we report the efficient enzymatic hydroxylation of CPA using the unspecific peroxygenase from Marasmius rotula (MroUPO) in a simple reaction design. Depending on the conditions used the primary liver metabolite 4-OH-CPA, its tautomer aldophosphamide (APA) and the overoxidized product 4-ketocyclophosphamide (4-keto-CPA) could be obtained. Using a kinetically controlled approach 4-OH-CPA was isolated with a yield of 32\% (purity > 97.6\%). Two human cancer cell lines (HepG2 and MCF-7) were treated with purified 4-OH-CPA produced by MroUPO (4-OH-CPAUPO). 4-OH-CPAUPO-induced cytotoxicity as measured by a luminescent cell viability assay and its genotoxicity as measured by γH2AX foci formation was not significantly different to the commercially available standard. The high yield of 4-OH-CPAUPO and its biological activity demonstrate that UPOs can be efficiently used to produce CYP-specific drug metabolites for pharmacological assessment.}, language = {en} } @misc{LauRangarajanKruegerGengeetal., author = {Lau, S. and Rangarajan, R. and Kr{\"u}ger-Genge, Anne and Braune, Steffen and K{\"u}pper, Jan-Heiner and Lendlein, Andreas and Jung, Friedrich}, title = {Age-related morphology and function of human arterial endothelial cells}, series = {Clinical Hemorheology and Microcirculation}, volume = {74}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1875-8622}, doi = {10.3233/CH-199238}, pages = {93 -- 107}, abstract = {Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies. In our approach, HAEC from 16 donors of varying age (16-63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status. No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p = 0.0374) and the membrane integrity marginally impaired (p = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors. According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly.}, language = {en} } @misc{KruegerGengeSteinbrechtJungetal., author = {Kr{\"u}ger-Genge, Anne and Steinbrecht, Susanne and Jung, Conrad H. G. and Westphal, Sophia and Kl{\"o}pzig, Stefanie and Waldeck, Peter and K{\"u}pper, Jan-Heiner and Storsberg, J. and Jung, Friedrich}, title = {Arthrospira platensis accelerates the formation of an endothelial cell monolayer and protects against endothelial cell detachment after bacterial contamination}, series = {Clinical Hemorheology and Microcirculation}, volume = {78}, journal = {Clinical Hemorheology and Microcirculation}, number = {2}, issn = {1386-0291}, doi = {10.3233/CH-201096}, pages = {151 -- 161}, abstract = {Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field.}, language = {en} } @misc{SchulzKruegerGengeLendleinetal., author = {Schulz, Christian and Kr{\"u}ger-Genge, Anne and Lendlein, Andreas and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture}, series = {International Journal of Molecular Science}, volume = {22}, journal = {International Journal of Molecular Science}, number = {3}, doi = {10.3390/ijms22031493}, pages = {15}, abstract = {The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90\% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used.}, language = {en} } @misc{BrauneKuepperJung, author = {Braune, Steffen and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Effect of Prostanoids on Human Platelet Function: An Overview}, series = {International Journal of Molecular Science}, volume = {21}, journal = {International Journal of Molecular Science}, number = {23}, doi = {10.3390/ijms21239020}, pages = {20}, abstract = {Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors.}, language = {en} } @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} } @misc{BrauneKruegerGengeKoehleretal., author = {Braune, Steffen and Kr{\"u}ger-Genge, Anne and K{\"o}hler, S. and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Effects of Arthrospira platensis-derived substances on blood cells}, series = {Clinical Hemorheology and Microcirculation}, volume = {85(2023)}, journal = {Clinical Hemorheology and Microcirculation}, number = {3}, issn = {1875-8622}, doi = {10.3233/CH-229103}, pages = {315 -- 321}, language = {en} } @misc{JungNghinaunyeWaldecketal., author = {Jung, C. G. H. and Nghinaunye, Theopolina and Waldeck, Peter and Braune, Steffen and Petrick, Ingolf and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Decarbonization of Arthrospira platensis production by using atmospheric CO2 as an exclusive carbon source: proof of principle}, series = {International Journal of Environmental Science and Technology}, journal = {International Journal of Environmental Science and Technology}, issn = {1735-2630}, doi = {10.1007/s13762-023-05215-x}, abstract = {There is an urgent need to develop technologies for removing CO2 from the atmosphere to combat climate change. Microalgae and cyanobacteria, such as Arthrospira platensis (AP), have shown promise due to their high photoautotrophic biomass production. Conventional AP culture media are supplemented with high concentrations of NaHCO3 since AP utilizes as a carbon source. These culture conditions result in significant amounts of CO2 escaping into the atmosphere, instead of being sequestered during cultivation. Here, we investigated whether ambient air (0.042\% CO2) can be used for growing AP in a culture medium lacking a fossil-based carbon source. AP was cultured in 2 L glass bioreactors containing: (1) Zarrouk medium with 16.8 g/L NaHCO3 and aeration with 0.236 vvm air with 2\% CO2 ("NaHCO3/CO2-based") to compensate carbon loss due to CO2 outgassing, and (2) Zarrouk medium without NaHCO3 and a gas flow with ambient air (0.926 vvm) as the only carbon source ("air-based"). The air-based production resulted in the biofixation of 3.78 gCO2/L during the linear growth phase. With NaHCO3/CO2-based production, a comparable amount of 3.42 gCO2/L was obtained while 659.12 g of CO2 was released into the atmosphere. Total protein, phycocyanin, chlorophyll-a, and carotenoids were present in similar or increased amounts in AP produced by the air-based method. We concluded that cultivation of AP with Zarrouk medium lacking NaHCO3 but using ambient air with atmospheric CO2 as the only carbon source is possible without reducing productivity. These results improve our understanding of how atmospheric CO2 can be reduced by culturing AP.}, language = {en} } @misc{HaasAckermannKuepperetal., author = {Haas, Manuel and Ackermann, Gabriel and K{\"u}pper, Jan-Heiner and Glatt, Hansruedi and Schrenk, Dieter and Fahrer, J{\"o}rg}, title = {OCT1-dependent uptake of structurally diverse pyrrolizidine alkaloids in human liver cells is crucial for their genotoxic and cytotoxic effects}, series = {Archives of Toxicology}, volume = {97}, journal = {Archives of Toxicology}, number = {12}, issn = {1432-0738}, doi = {10.1007/s00204-023-03591-4}, pages = {3259 -- 3271}, abstract = {Pyrrolizidine alkaloids (PAs) are important plant hepatotoxins, which occur as contaminants in plant-based foods, feeds and phytomedicines. Numerous studies demonstrated that the genotoxicity and cytotoxicity of PAs depend on their chemical structure, allowing for potency ranking and grouping. Organic cation transporter-1 (OCT1) was previously shown to be involved in the cellular uptake of the cyclic PA diesters monocrotaline, retrorsine and senescionine. However, little is known about the structure-dependent transport of PAs. Therefore, we investigated the impact of OCT1 on the uptake and toxicity of three structurally diverse PAs (heliotrine, lasiocarpine and riddelliine) differing in their degree and type of esterification in metabolically competent human liver cell models and hamster fibroblasts. Human HepG2-CYP3A4 liver cells were exposed to the respective PA in the presence or absence of the OCT1-inhibitors D-THP and quinidine, revealing a strongly attenuated cytotoxicity upon OCT1 inhibition. The same experiments were repeated in V79-CYP3A4 hamster fibroblasts, confirming that OCT1 inhibition prevents the cytotoxic effects of all tested PAs. Interestingly, OCT1 protein levels were much lower in V79-CYP3A4 than in HepG2-CYP3A4 cells, which correlated with their lower susceptibility to PA-induced cytotoxicity. The cytoprotective effect of OCT1 inhibiton was also demonstrated in primary human hepatocytes following PA exposure. Our experiments further showed that the genotoxic effects triggered by the three PAs are blocked by OCT1 inhibition as evidenced by strongly reduced γH2AX and p53 levels. Consistently, inhibition of OCT1-mediated uptake suppressed the activation of the DNA damage response (DDR) as revealed by decreased phosphorylation of checkpoint kinases upon PA treatment. In conclusion, we demonstrated that PAs, independent of their degree of esterification, are substrates for OCT1-mediated uptake into human liver cells. We further provided evidence that OCT1 inhibition prevents PA-triggered genotoxicity, DDR activation and subsequent cytotoxicity. These findings highlight the crucial role of OCT1 together with CYP3A4-dependent metabolic activation for PA toxicity.}, language = {en} } @misc{JungWaldeckPetricketal., author = {Jung, Conrad H. G. and Waldeck, Peter and Petrick, Ingolf and Akinwunmi, Mosunmol and Braune, Steffen and Jung, Friedrich and K{\"u}pper, Jan-Heiner}, title = {Light-induced changes in the morphology and fluorescence of Arthrospira platensis}, series = {Clinical Hemorheology and Microcirculation}, volume = {9}, journal = {Clinical Hemorheology and Microcirculation}, number = {1}, issn = {1386-0291}, doi = {10.3233/JCB-239001}, pages = {71 -- 77}, abstract = {The cyanobacterium Arthrospira platensis is a well-known source of bioactive substances. Growth and the generation of bioactive ingredients of Arthrospira platensis depend mainly on the quantity of light in a controlled environment. Photoinhibition is a time, nutrient, and light intensity-dependent decrease in photosynthetic efficiency. However, too strong illumination can induce two harmful effects: (1) photoinhibition as a reduction in photosynthetic rate and (2) photooxidation which can have lethal effects on the cells, and which can lead to total loss of the culture. The results of this microscopical study demonstrate, that under the procedures described and very high photon flux den-sities, not only a decrease in the photosynthetic efficiency but beyond, also destruction of Arthrospira platensis can occur.}, language = {en} } @misc{RoselliniSchulzeOmeretal., author = {Rosellini, Matteo and Schulze, Alicia and Omer, Ejlal A. and Ali, Nadeen T. and Marini, Federico and K{\"u}pper, Jan-Heiner and Efferth, Thomas}, title = {The effect of plastic-related compounds on transcriptome-wide gene expression on CYP2C19-overexpressing HepG2 cells}, series = {Molecules}, volume = {28}, journal = {Molecules}, number = {16}, issn = {1420-3049}, doi = {10.3390/molecules28165952}, abstract = {In recent years, plastic and especially microplastic in the oceans have caused huge problems to marine flora and fauna. Recently, such particles have also been detected in blood, breast milk, and placenta, underlining their ability to enter the human body, presumably via the food chain and other yet-unknown mechanisms. In addition, plastic contains plasticizers, antioxidants, or lubricants, whose impact on human health is also under investigation. At the cellular level, the most important enzymes involved in the metabolism of xenobiotic compounds are the cytochrome P450 monooxygenases (CYPs). Despite their extensive characterization in the maintenance of cellular balance, their interactions with plastic and related products are unexplored. In this study, the possible interactions between several plastic-related compounds and one of the most important cytochromes, CYP2C19, were analyzed. By applying virtual compound screening and molecular docking to more than 1000 commercially available plastic-related compounds, we identified candidates that are likely to interact with this protein. A growth inhibition assay confirmed their cytotoxic activity on a CYP2C19-transfected hepatic cell line. Subsequently, we studied the effect of the selected compounds on the transcriptome-wide gene expression level by conducting RNA sequencing. Three candidate molecules were identified, i.e., 2,2′-methylene bis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl) ethane, and 2,2′-methylene bis(6-cyclohexyl-4-methylphenol)), which bound with a high affinity to CYP2C19 in silico. They exerted a profound cytotoxicity in vitro and interacted with several metabolic pathways, of which the 'cholesterol biosynthesis process' was the most affected. In addition, other affected pathways involved mitosis, DNA replication, and inflammation, suggesting an increase in hepatotoxicity. These results indicate that plastic-related compounds could damage the liver by affecting several molecular pathways.}, 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{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{BuchmuellerEngePetersetal., author = {Buchmueller, Julia and Enge, Anne-Margarethe and Peters, Antonia and Ebmeyer, Johanna and K{\"u}pper, Jan-Heiner and Sch{\"a}fer, Bernd and Br{\"a}uning, Albert and Hessel-Pras, Stefanie}, title = {The chemical structure impairs the intensity of genotoxic effects promoted by 1,2-unsaturated pyrrolizidine alkaloids in vitro}, series = {Food and Chemical Toxicology}, volume = {Vol. 164}, journal = {Food and Chemical Toxicology}, issn = {1873-6351}, doi = {10.1016/j.fct.2022.113049}, language = {en} } @misc{AbdelfatahNassKnorzetal., author = {Abdelfatah, Sara and Nass, Janine and Knorz, Caroline and Klauck, Sabine M. and K{\"u}pper, Jan-Heiner and Efferth, Thomas}, title = {Pyrrolizidine alkaloids cause cell cycle and DNA damage repair defects as analyzed by transcriptomics in cytochrome P450 3A4-overexpressing HepG2 clone 9 cells}, series = {Cell biology and toxicology}, volume = {38}, journal = {Cell biology and toxicology}, number = {2}, issn = {1573-6822}, doi = {10.1007/s10565-021-09599-9}, pages = {325 -- 345}, language = {en} } @misc{GeburekRutzGaoetal., author = {Geburek, Ina and Rutz, Lukas and Gao, Lan and K{\"u}pper, Jan-Heiner and These, Anja and Schrenk, Dieter}, title = {The metabolic pattern of hepatotoxic pyrrolizidine alkaloids in liver cells}, series = {Chemical Research in Toxicology}, volume = {34}, journal = {Chemical Research in Toxicology}, number = {4}, doi = {10.1021/acs.chemrestox.0c00507}, pages = {1101 -- 1113}, abstract = {Contamination with 1,2-unsaturated pyrrolizidine alkaloids (PAs) is a serious problem for certain phytomedicines, foods, and animal feeds. Several of these PAs are genotoxic and carcinogenic, primarily in the liver, upon cytochrome P450 (CYP)-catalyzed activation into reactive (pyrrolic and pyrrole-like) metabolites. Here we investigated the metabolism of selected PAs (echimidine, europine, lasiocarpine, lycopsamine, retrorsine, and senecionine) in rat hepatocytes in primary culture and in human CYP3A4-transfected HepG2 cells. The open-chained diesters echimidine and lasiocarpine and the cyclic diester senecionine were extensively metabolized in rat hepatocytes into a broad spectrum of products released into the medium. A large portion of unidentified, possibly irreversibly bound, products remained in the cells while detectable amounts of reactive and other metabolites were found in the incubation media. In HepG2-CYP3A4 cells, lasiocarpine was more extensively metabolized than echimidine and senecionine which also gave rise to the release of pyrrolic metabolites. In human cells, no pyrrolic metabolites were detected in retrorsine or lycopsamine incubations, while no such metabolites were detected from europine in both cell types. Other types of metabolic changes comprised modifications such as side chain demethylation or oxygenation reactions like the formation of N-oxides. The latter, considered as a detoxification step, was a major pathway with cyclic diesters, was less distinctive for echimidine and lycopsamine and almost negligible for lasiocarpine and europine. Our data are in agreement with previously published cyto- and genotoxicity findings and suggests that the metabolic pattern may contribute substantially to the specific toxic potency of a certain congener. In addition, marked differences were found for certain congeners between rat hepatocytes and transfected human HepG2 cells, whereby a high level of bioactivation was found for lasiocarpine, whereas a very low level of bioactivation was observed for monoesters, in particular in human cells.}, language = {en} } @misc{JungWaldeckPetricketal., author = {Jung, Conrad H. G. and Waldeck, Peter and Petrick, Ingolf and Braune, Steffen and K{\"u}pper, Jan-Heiner and Jung, Friedrich}, title = {Bioreactor for the cultivation of Arthrospira platensis under controlled conditions}, series = {Journal of Cellular Biotechnology}, volume = {7}, journal = {Journal of Cellular Biotechnology}, number = {1}, doi = {10.3233/JCB-210032}, pages = {35 -- 40}, abstract = {A vertical flat-type bioreactor consisting of transparent polyethylene (food safe) was constructed, which is characterized by a flexible design and allows the adjustment of a light path of 1 cm - 8.5 cm and a working volume of 1.5 l - 4 l. To characterize the performance of the bioreactor, cultivation experiments were performed with the cyanobacterium Arthrospira platensis (AP). The growth was assessed continuously by monitoring optical density and intermittently by measuring the dry weight of the AP biomass. An on-line measurement technique for estimating biomass production rate in a photosynthetic microalgae culture was developed. The oxygen produced by AP in the culture medium was flushed out sparging using a mixture of air and CO2 (1\%). Factors which might influence the AP growth were monitored: pH, temperature, oxygen concentration and the filling level were corrected automatically to compensate evaporation losses. As an example, the huge influence of the light intensity on the AP growth was tested. The increase of the photon flux density of 15 to 1200μmol/(l · d) led to a 22-fold increase of the productivity and a 3.1-fold shorter doubling time. Using an online measurement technique - together with the control of the growth process via a wireless local area network (WLAN) router and virtual private network - allows monitoring the growth of Arthrospira platensis remotely.}, language = {en} } @misc{BrauneKruegerGengeKammereretal., author = {Braune, Steffen and Kr{\"u}ger-Genge, Anne and Kammerer, Sarah and Jung, Friedrich and K{\"u}pper, Jan-Heiner}, title = {Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies}, series = {Life}, volume = {11}, journal = {Life}, number = {2}, doi = {10.3390/life11020091}, pages = {91}, 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{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{KruegerGengeSteinbrechtKuepperetal., author = {Kr{\"u}ger-Genge, Anne and Steinbrecht, Susanne and K{\"u}pper, Jan-Heiner and Lendlein, Andreas and Jung, Friedrich}, title = {Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: preliminary in vitro results.}, series = {Clinical Hemorheology and Microcirculation}, volume = {69}, journal = {Clinical Hemorheology and Microcirculation}, number = {1-2}, issn = {1875-8622}, doi = {10.3233/CH-189125}, pages = {267 -- 276}, language = {en} } @misc{JungJungKruegerGengeetal., author = {Jung, Friedrich and Jung, Conrad H. G. and Kr{\"u}ger-Genge, Anne and Waldeck, Peter and K{\"u}pper, Jan-Heiner}, title = {Factors influencing the growth of Spirulina platensis in closed photobioreactors under CO₂ - O₂ conversion}, series = {Journal of Cellular Biotechnology}, volume = {5}, journal = {Journal of Cellular Biotechnology}, number = {2}, issn = {2352-3697}, doi = {10.3233/JCB-199004}, pages = {125 -- 134}, abstract = {Since there is growing interest throughout the world in photosynthetic microbes as a potential source of food or food supplements, an assessment of factors which influence the biomass obtained in bioreactors, protein contents and constituents is important. This work reviews the autotrophic cultivation conditions of Spirulina platensis especially the dependency on the strain, the composition of the nutrient solution, pH, temperature of the medium, light intensity and color as well as exposure rhythm, the flow rate and composition of the aerating gas mixture and the bubble size, the content of oxygen, CO₂ and HCO₃ in the medium and last but not least from the optical density of the spirulina suspension during growth.}, language = {en} } @misc{SteinbrechtKoenigSchmidtkeetal., author = {Steinbrecht, Susanne and K{\"o}nig, Rosalie and Schmidtke, Kai-Uwe and Herzog, Natalie and Scheibner, Katrin and Kr{\"u}ger-Genge, Anne and Jung, Friedrich and Kammerer, Sarah and K{\"u}pper, Jan-Heiner}, title = {Metabolic activity testing can underestimate acute drug cytotoxicity as revealed by HepG2 cell clones overexpressing cytochrome P450 2C19 and 3A4}, series = {Toxicology}, volume = {412}, journal = {Toxicology}, issn = {0300-483X}, doi = {10.1016/j.tox.2018.11.008}, pages = {37 -- 47}, language = {en} } @misc{KammererKuepper, author = {Kammerer, Sarah and K{\"u}pper, Jan-Heiner}, title = {Optimized protocol for induction of cytochrome P450 enzymes 1A2 and 3A4 in human primary-like hepatocyte cell strain HepaFH3 to study in vitro toxicology}, series = {Clinical Hemorheology and Microcirculation}, volume = {70}, journal = {Clinical Hemorheology and Microcirculation}, number = {4}, issn = {1386-0291}, doi = {10.3233/CH-189321}, pages = {563 -- 571}, language = {en} } @misc{KruegerGengeJungKuepperetal., author = {Kr{\"u}ger-Genge, Anne and Jung, Friedrich and K{\"u}pper, Jan-Heiner and Lehmann, Christian and Franke, Ralf-Peter}, title = {Actin type and distribution in erythrocytes}, series = {Journal of Cellular Biotechnology}, volume = {3}, journal = {Journal of Cellular Biotechnology}, number = {2}, issn = {2352-3697}, doi = {10.3233/JCB-179014}, pages = {81 -- 83}, abstract = {Erythrocytes transport oxygen from the lungs to the tissues. The excess surface area together with the elasticity of the erythrocyte cell membrane provides the flexibility needed to pass through the microvasculature where the oxygen exchange occurs. Although the architecture of the red cell and its membrane-associated cytoskeletal network is known in general, the factors that control the characteristic shape change during echinocyte formation are poorly understood. In this short report we show that in echinocytes a completely reorganized membrane cytoskeleton with a box-like structure of actin filaments prevailed indicating the importance of the actin cytoskeleton during echinocyte formation.}, language = {en} } @misc{KruegerGengeBrauneWalteretal., author = {Kr{\"u}ger-Genge, Anne and Braune, Steffen and Walter, Maria and Kratz, Karl and K{\"u}pper, Jan-Heiner and Krengel, M. and Lendlein, Andreas and Jung, Friedrich}, title = {Influence of surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability}, series = {Clinical Hemorheology and Microcirculation}, volume = {69}, journal = {Clinical Hemorheology and Microcirculation}, number = {1-2}, issn = {1875-8622}, doi = {10.3233/CH-189130}, pages = {305 -- 316}, language = {en} } @misc{NowakKammererKuepper, author = {Nowak, Elisabeth and Kammerer, Sarah and K{\"u}pper, Jan-Heiner}, title = {ATP-based cell viability assay is superior to trypan blue exclusion and XTT assay in measuring cytotoxicity of anticancer drugs Taxol and Imatinib, and proteasome inhibitor MG-132 on human hepatoma cell line HepG2.}, series = {Clinical Hemorheology and Microcirculation}, volume = {69}, journal = {Clinical Hemorheology and Microcirculation}, number = {1-2}, issn = {1386-0291}, doi = {10.3233/CH-189120}, pages = {327 -- 336}, language = {en} } @misc{UhligGehreKammereretal., author = {Uhlig, Katja and Gehre, Christian P. and Kammerer, Sarah and K{\"u}pper, Jan-Heiner and Coleman, D. and P{\"u}schel, G. and Duschl, Claus}, title = {Real-time monitoring of oxygen consumption of hepatocytes in a microbioreactor}, series = {Toxicology Letters}, volume = {295}, journal = {Toxicology Letters}, number = {Supplement 1}, issn = {0378-4274}, doi = {10.1016/j.toxlet.2018.06.652}, pages = {S115}, language = {en} } @misc{Kuepper, author = {K{\"u}pper, Jan-Heiner}, title = {Vorrichtung und Verfahren zur Sequestrierung von atmosph{\"a}rischen Kohlendioxid}, language = {de} }