TY - JOUR A1 - Meyer, S. A1 - Raber, G. A1 - Ebert, Franziska A1 - Leffers, L. A1 - Müller, Sandra Marie A1 - Taleshi, M. S. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites JF - Toxicology research N2 - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids. Y1 - 2015 U6 - https://doi.org/10.1039/c5tx00122f SN - 2045-4538 VL - 5 IS - 4 SP - 1289 EP - 1296 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Meyer, S. A1 - Raber, G. A1 - Ebert, Franziska A1 - Leffers, L. A1 - Müller, Sandra Marie A1 - Taleshi, M. S. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites N2 - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 199 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-82008 ER - TY - JOUR A1 - Braune, Steffen A1 - Latour, Robert A. A1 - Reinthaler, Markus A1 - Landmesser, Ulf A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - In Vitro Thrombogenicity Testing of Biomaterials JF - Advanced healthcare materials N2 - The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed. KW - biomaterials KW - blood tests KW - implants KW - in vitro KW - thrombogenicity Y1 - 2019 U6 - https://doi.org/10.1002/adhm.201900527 SN - 2192-2640 SN - 2192-2659 VL - 8 IS - 21 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Niedl, Robert Raimund A1 - Beta, Carsten T1 - Hydrogel-driven paper-based microfluidics N2 - Paper-based microfluidics provide an inexpensive, easy to use technology for point-of-care diagnostics in developing countries. Here, we combine paper-based microfluidic devices with responsive hydrogels to add an entire new class of functions to these versatile low-cost fluidic systems. The hydrogels serve as fluid reservoirs. In response to an external stimulus, e.g. an increase in temperature, the hydrogels collapse and release fluid into the structured paper substrate. In this way, chemicals that are either stored on the paper substrate or inside the hydrogel pads can be dissolved, premixed, and brought to reaction to fulfill specific analytic tasks. We demonstrate that multi-step sequences of chemical reactions can be implemented in a paper-based system and operated without the need for external precision pumps. We exemplify this technology by integrating an antibody-based E. coli test on a small and easy to use paper device. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 193 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-81083 SP - 2452 EP - 2459 ER - TY - JOUR A1 - Niedl, Robert Raimund A1 - Beta, Carsten T1 - Hydrogel-driven paper-based microfluidics JF - LAB on a chip : miniaturisation for chemistry and biology N2 - Paper-based microfluidics provide an inexpensive, easy to use technology for point-of-care diagnostics in developing countries. Here, we combine paper-based microfluidic devices with responsive hydrogels to add an entire new class of functions to these versatile low-cost fluidic systems. The hydrogels serve as fluid reservoirs. In response to an external stimulus, e.g. an increase in temperature, the hydrogels collapse and release fluid into the structured paper substrate. In this way, chemicals that are either stored on the paper substrate or inside the hydrogel pads can be dissolved, premixed, and brought to reaction to fulfill specific analytic tasks. We demonstrate that multi-step sequences of chemical reactions can be implemented in a paper-based system and operated without the need for external precision pumps. We exemplify this technology by integrating an antibody-based E. coli test on a small and easy to use paper device. Y1 - 2015 U6 - https://doi.org/10.1039/c5lc00276a SN - 1473-0197 SN - 1473-0189 VL - 11 IS - 15 SP - 2452 EP - 2459 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Reichetzeder, Christoph A1 - Prehn, Cornelia A1 - von Websky, Karoline A1 - Slowinski, Torsten A1 - Chen, You-Peng A1 - Yin, Liang-Hong A1 - Kleuser, Burkhard A1 - Yang, Xue-Song A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Fetal serum metabolites are independently associated with Gestational diabetes mellitus JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel KW - Gestational diabetes KW - Metabolomics KW - Phosphatidylcholine acyl-alkyl C 32:1 KW - Proline Y1 - 2018 U6 - https://doi.org/10.1159/000487119 SN - 1015-8987 SN - 1421-9778 VL - 45 IS - 2 SP - 625 EP - 638 PB - Karger CY - Basel ER - TY - JOUR A1 - Lau, Skadi A1 - Maier, Anna A1 - Braune, Steffen A1 - Gossen, Manfred A1 - Lendlein, Andreas T1 - Effect of endothelial culture medium composition on platelet responses to polymeric biomaterials JF - International journal of molecular sciences N2 - Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT. KW - cyclic olefin copolymer KW - poly(tetrafluoroethylene) KW - endothelial cells KW - platelets KW - in vitro thrombogenicity testing Y1 - 2021 U6 - https://doi.org/10.3390/ijms22137006 SN - 1422-0067 SN - 1661-6596 VL - 22 IS - 13 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Deng, Zijun A1 - Zou, Jie A1 - Wang, Weiwei A1 - Nie, Yan A1 - Tung, Wing-Tai A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Dedifferentiation of mature adipocytes with periodic exposure to cold JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10 degrees C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37 degrees C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1 alpha, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37 degrees C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells. KW - Adipocyte KW - dedifferentiation KW - cold KW - lipid Y1 - 2019 U6 - https://doi.org/10.3233/CH-199005 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 4 SP - 415 EP - 424 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Reichetzeder, Christoph A1 - Prehn, Cornelia A1 - Yin, Liang-Hong A1 - Yun, Chen A1 - Zeng, Shufei A1 - Chu, Chang A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel KW - Metabolomics KW - Lysophosphatidylcholine KW - Birth Weight KW - DOHaD KW - Hypertension KW - Type 2 Diabetes Y1 - 2018 U6 - https://doi.org/10.1159/000487118 SN - 1015-8987 SN - 1421-9778 VL - 45 IS - 2 SP - 614 EP - 624 PB - Karger CY - Basel ER - TY - JOUR A1 - Bhuvanesh, Thanga A1 - Machatschek, Rainhard Gabriel A1 - Lysyakova, Liudmila A1 - Kratz, Karl A1 - Schulz, Burkhard A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion JF - Biomedical materials : materials for tissue engineering and regenerative medicine N2 - In biomaterial development, the design of material surfaces that mimic the extra-cellular matrix (ECM) in order to achieve favorable cellular instruction is rather challenging. Collagen-type IV (Col-IV), the major scaffolding component of Basement Membranes (BM), a specialized ECM with multiple biological functions, has the propensity to form networks by self-assembly and supports adhesion of cells such as endothelial cells or stem cells. The preparation of biomimetic Col-IV network-like layers to direct cell responses is difficult. We hypothesize that the morphology of the layer, and especially the density of the available adhesion sites, regulates the cellular adhesion to the layer. The Langmuir monolayer technique allows for preparation of thin layers with precisely controlled packing density at the air-water (A-W) interface. Transferring these layers onto cell culture substrates using the Langmuir-Schafer (LS) technique should therefore provide a pathway for preparation of BM mimicking layers with controlled cell adherence properties. In situ characterization using ellipsometry and polarization modulation-infrared reflection absorption spectroscopy of Col-IV layer during compression at the A-W interface reveal that there is linear increase of surface molecule concentration with negligible orientational changes up to a surface pressure of 25 mN m(-1). Smooth and homogeneous Col-IV network-like layers are successfully transferred by LS method at 15 mN m(-1) onto poly(ethylene terephthalate) (PET), which is a common substrate for cell culture. In contrast, the organization of Col-IV on PET prepared by the traditionally employed solution deposition method results in rather inhomogeneous layers with the appearance of aggregates and multilayers. Progressive increase in the number of early adherent mesenchymal stem cells (MSCs) after 24 h by controlling the areal Col-IV density by LS transfer at 10, 15 and 20 mN m(-1) on PET is shown. The LS method offers the possibility to control protein characteristics on biomaterial surfaces such as molecular density and thereby, modulate cell responses. KW - collagen-IV KW - basement membrane KW - Langmuir-Schafer films KW - stem cell adhesion KW - protein KW - ellipsometry Y1 - 2019 U6 - https://doi.org/10.1088/1748-605X/aaf464 SN - 1748-6041 SN - 1748-605X VL - 14 IS - 2 PB - Inst. of Physics Publ. CY - Bristol ER -