TY - JOUR A1 - Zhou, Suqiong A1 - Pan, Yuanwei A1 - Zhang, Jianguang A1 - Li, Yan A1 - Neumann, Falko A1 - Schwerdtle, Tanja A1 - Li, Wenzhong A1 - Haag, Rainer T1 - Dendritic polyglycerol-conjugated gold nanostars with different densities of functional groups to regulate osteogenesis in human mesenchymal stem cells JF - Nanoscale N2 - Nanomaterials play an important role in mimicking the biochemical and biophysical cues of the extracellular matrix in human mesenchymal stem cells (MSCs). Increasing studies have demonstrated the crucial impact of functional groups on MSCs, while limited research is available on how the functional group's density on nanoparticles regulates MSC behavior. Herein, the effects of dendritic polyglycerol (dPG)-conjugated gold nanostars (GNSs) with different densities of functional groups on the osteogenesis of MSCs are systematically investigated. dPG@GNS nanocomposites have good biocompatibility and the uptake by MSCs is in a functional group density-dependent manner. The osteogenic differentiation of MSCs is promoted by all dPG@GNS nanocomposites, in terms of alkaline phosphatase activity, calcium deposition, and expression of osteogenic protein and genes. Interestingly, the dPGOH@GNSs exhibit a slight upregulation in the expression of osteogenic markers, while the different charged densities of sulfate and amino groups show more efficacy in the promotion of osteogenesis. Meanwhile, the sulfated nanostars dPGS20@GNSs show the highest enhancement. Furthermore, various dPG@GNS nanocomposites exerted their effects by regulating the activation of Yes-associated protein (YAP) to affect osteogenic differentiation. These results indicate that dPG@GNS nanocomposites have functional group density-dependent influence on the osteogenesis of MSCs, which may provide a new insight into regulating stem cell fate. Y1 - 2020 U6 - https://doi.org/10.1039/d0nr06570f SN - 2040-3364 SN - 2040-3372 VL - 12 IS - 47 SP - 24006 EP - 24019 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Ebert, Franziska A1 - Ziemann, Vanessa A1 - Wandt, Viktoria Klara Veronika A1 - Witt, Barbara A1 - Müller, Sandra Marie A1 - Guttenberger, Nikolaus A1 - Bankoglu, Ezgi Eyluel A1 - Stopper, Helga A1 - Raber, Georg A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon JF - Journal of trace elements in medicine and biology N2 - Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified. Y1 - 2017 U6 - https://doi.org/10.1016/j.jtemb.2020.126563 VL - 61 PB - Elsevier CY - München ER - TY - JOUR A1 - Kotthoff, Lisa A1 - O'Callaghan, Sarah-Louise A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown. KW - veterinary drug KW - moxidectin KW - transformation products KW - electrochemistry KW - photochemistry KW - LC KW - HRMS Y1 - 2020 U6 - https://doi.org/10.1007/s00216-020-02572-1 SN - 1618-2642 SN - 1618-2650 VL - 412 IS - 13 SP - 3141 EP - 3152 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Rausch, Ann-Kristin A1 - Brockmeyer, Robert A1 - Schwerdtle, Tanja T1 - Development and Validation of a QuEChERS-Based Liquid Chromatography Tandem Mass Spectrometry Multi-Method for the Determination of 38 Native and Modified Mycotoxins in Cereals JF - Journal of Agricultural and Food Chemistry N2 - Here, a reliable and sensitive method for the determination of 38 (modified) mycotoxins was developed. Using a QuEChERS-based extraction method [acetonitrile/water/formic acid (75:20:5, v/v/v)], followed by two runs of high performance liquid chromatography tandem mass spectrometry with different conditions, relevant mycotoxins in cereals were analyzed. The method was validated according to the performance criteria defined by the European Commission (EC) in Commission Decision no. 657/2002. Limits of quantification ranged from 0.05 to 150 μg/kg. Good linearity (R2 > 0.99), recovery (61–120%), repeatability (RSDr < 15%), and reproducibility (RSDR < 20%) were obtained for most mycotoxins. However, validation results for Alternaria toxins and fumonisins were unsatisfying. Matrix effects (−69 to +59%) were compensated for using standard addition. Application on reference materials gave correct results while analysis of samples from local retailers revealed contamination, especially with deoxynivalenol, deoxynivalenol-3-glucoside, fumonisins, and zearalenone, in concentrations up to 369, 58, 1002, and 21 μg/kg, respectively. KW - multi-mycotoxin analysis KW - modified mycotoxins KW - QuEChERS KW - LC−MS/MS KW - cereals KW - validation Y1 - 2020 U6 - https://doi.org/10.1021/acs.jafc.9b07491 SN - 0021-8561 VL - 68 IS - 16 SP - 4657 EP - 4669 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Dünkelberg, Sophie A1 - Maywald, Martina A1 - Schmitt, Anne Kristina A1 - Schwerdtle, Tanja A1 - Meyer, Sören A1 - Rink, Lothar T1 - The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium. Methods and Results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways. KW - Foxp3 KW - regulatory T cells KW - sodium KW - T helper 17 cells KW - zinc Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.201900245 SN - 1613-4133 VL - 64 IS - 2 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Finke, Hannah A1 - Wandt, Viktoria Klara Veronika A1 - Ebert, Franziska A1 - Guttenberger, Nikolaus A1 - Glabonjat, Ronald A. A1 - Stiboller, Michael A1 - Francesconi, Kevin A. A1 - Raber, Georg A1 - Schwerdtle, Tanja T1 - Toxicological assessment of arsenic-containing phosphatidylcholines in HepG2 cells N2 - Arsenolipids include a wide range of organic arsenic species that occur naturally in seafood and thereby contribute to human arsenic exposure. Recently arsenic-containing phosphatidylcholines (AsPCs) were identified in caviar, fish, and algae. In this first toxicological assessment of AsPCs, we investigated the stability of both the oxo- and thioxo-form of an AsPC under experimental conditions, and analyzed cell viability, indicators of genotoxicity and biotransformation in human liver cancer cells (HepG2). Precise toxicity data could not be obtained owing to the low solubility in the cell culture medium of the thioxo-form, and the ease of hydrolysis of the oxo-form, and to a lesser degree the thioxo-form. Hydrolysis resulted amongst others in the respective constituent arsenic-containing fatty acid (AsFA). Incubation of the cells with oxo-AsPC resulted in a toxicity similar to that determined for the hydrolysis product oxo-AsFA alone, and there were no indices for genotoxicity. Furthermore, the oxo-AsPC was readily taken up by the cells resulting in high cellular arsenic concentrations (50 μM incubation: 1112 ± 146 μM As cellular), whereas the thioxo-AsPC was substantially less bioavailable (50 μM incubation: 293 ± 115 μM As cellular). Speciation analysis revealed biotransformation of the AsPCs to a series of AsFAs in the culture medium, and, in the case of the oxo-AsPC, to as yet unidentified arsenic species in cell pellets. The results reveal the difficulty of toxicity studies of AsPCs in vitro, indicate that their toxicity might be largely governed by their arsenic fatty acid content and suggest a multifaceted human metabolism of food derived complex arsenolipids. KW - Biochemistry KW - Biological Sciences KW - Science and Mathematics KW - Books KW - Journals Y1 - 2020 U6 - https://doi.org/10.1039/d0mt00073f VL - 12 IS - 7 SP - 1159 EP - 1170 PB - Oxford University CY - Cambridge ER - TY - JOUR A1 - Finke, Hannah A1 - Winkelbeiner, Nicola Lisa A1 - Lossow, Kristina A1 - Hertel, Barbara A1 - Wandt, Viktoria Klara Veronika A1 - Schwarz, Maria A1 - Pohl, Gabriele A1 - Kopp, Johannes Florian A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice BT - trace element status, genomic stability, inflammation, and epigenetics JF - Molecular nutrition & food research N2 - Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass‐spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron‐related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects. Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.202000325 SN - 1613-4125 VL - 64 IS - 16 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Müller, Anke Katharina A1 - Helms, Ute A1 - Rohrer, Carsten A1 - Möhler, Monika A1 - Hellwig, Frank A1 - Glei, Michael A1 - Schwerdtle, Tanja A1 - Lorkowski, Stefan A1 - Dawczynski, Christine T1 - Nutrient composition of different hazelnut cultivars grown in Germany JF - Foods N2 - Hazelnuts are rarely cultivated in Germany, although they are a valuable source for macro- and micronutrients and can thus contribute to a healthy diet. Near the present, 15 varieties were cultivated in Thuringia, Germany, as a pilot study for further research. The aim of our study was to evaluate the micro- and macronutrient composition of representative, randomly mixed samples of the 15 different hazelnut cultivars. Protein, fat, and fiber contents were determined using established methods. Fatty acids, tocopherols, minerals, trace elements, and ultra-trace elements were analyzed using gas chromatography, high-performance liquid chromatography, and inductively coupled plasma triple quadrupole mass-spectrometry, respectively. We found that the different hazelnut varieties contained valuable amounts of fat, protein, dietary fiber, minerals, trace elements, and alpha-tocopherol, however, in different quantities. The variations in nutrient composition were independent of growth conditions, which were identical for all hazelnut varieties. Therefore, each hazelnut cultivar has its specific nutrient profile. KW - Corylus avellana L. KW - nutrient composition KW - hazelnut cultivars KW - minerals KW - tocopherols Y1 - 2020 U6 - https://doi.org/10.3390/foods9111596 SN - 2304-8158 VL - 9 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Witt, Barbara A1 - Schaumlöffel, Dirk A1 - Schwerdtle, Tanja T1 - Subcellular Localization of Copper BT - Cellular Bioimaging with Focus on Neurological Disorders JF - International Journal of Molecular Sciences N2 - As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences. KW - copper KW - cellular bioimaging KW - neurodegenerative diseases KW - copper-related disorders KW - SIMS techniques KW - TEM KW - S-XRF Y1 - 2020 U6 - https://doi.org/10.3390/ijms21072341 SN - 1422-0067 VL - 21 IS - 7 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Müller, Sandra A1 - Dawczynski, Christine A1 - Wiest, Johanna A1 - Lorkowski, Stefan A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study JF - Nutrients N2 - Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se KW - Se KW - selenoprotein P KW - GPx activity KW - cardiovascular disease KW - status markers Y1 - 2020 U6 - https://doi.org/10.3390/nu12030676 SN - 2072-6643 VL - 12 IS - 3 PB - MDPI CY - Basel ER -