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1.
Anne-Margarethe Enge Florian Kaltner Christoph Gottschalk Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(8)
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. 相似文献
2.
Matteo Di Giosia Alice Soldà Markus Seeger Andrea Cantelli Fabio Arnesano Maria I. Nardella Vincenzo Mangini Francesco Valle Marco Montalti Francesco Zerbetto Stefania Rapino Matteo Calvaresi Vasilis Ntziachristos 《Advanced functional materials》2021,31(20):2101527
Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV-visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications. 相似文献
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Christoph Gottschalk Aiko Huckauf Arne Dübecke Florian Kaltner Matthias Zimmermann Ines Rahaus 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(7):1366-1383
The contamination of honey with hepatotoxic pyrrolizidine alkaloids (PAs) is a well-known hazard for food safety. While management strategies and controls of the honey industry aim to reduce the PA levels, uncertainties remain with regard to the safety of regionally produced and marketed honey. In addition, a previous study showed large differences of results obtained after various periods of storage and apparent differences between the analytical results of different laboratories. Therefore, this study aimed at examining these uncertainties by monitoring the impact of storage on the PA and PA N-oxide (PANO) content of two freshly harvested honeys and on possible demixing effects caused by pollen settling. Additionally, three analytical approaches – target analysis with matrix-matched calibration or standard addition and a sum parameter method – were applied for a comparative analysis of 20 honeys harvested in summer 2016. All samples originated from Schleswig-Holstein in Northern Germany where the PA plant Jacobaea vulgaris is currently observed on a massive scale. The results of the time series analyses showed that PANO levels markedly decreased within a few weeks and practically reached the LOD 16 weeks after harvest. Tertiary PAs, by contrast, remained stable and did not increase as a consequence of PANO decrease. The experiments on a putative demixing, which may result in a heterogeneous distribution of PAs/PANOs, revealed that there was no such effect during storage of up to 12 weeks. A comparison of the PA/PANO levels obtained by different analytical approaches showed that in some cases the sum parameter method yielded much higher levels than the target approaches, whereas in other cases, the target analysis with standard addition found higher levels than the other two methods. In summary, the results of this study highlight uncertainties regarding the validity and comparability of analytical results and consequently regarding health risk assessment. 相似文献
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6.
Paul Geoerg Florian Berchtold Steven Gwynne Karen Boyce Stefan Holl Anja Hofmann 《火与材料》2019,43(7):759-781
To quantify the evacuation process, evacuation practitioners use engineering egress data describing the occupant movement characteristics. These data are typically based to young and fit populations. However, the movement abilities of occupants who might be involved in evacuations are becoming more variable—with the building populations of today typically including increasing numbers of individuals: with impairments or who are otherwise elderly or generally less mobile. Thus, there will be an increasing proportion of building occupants with reduced ability to egress. For safe evacuation, there is therefore a need to provide valid engineering egress data considering pedestrians with disabilities. Gwynne and Boyce recently compiled a series of data sets related to the evacuation process to support practitioner activities in the chapter Engineering Data in the SFPE Handbook of Fire Protection Engineering. This paper supplements these data sets by providing information on and presenting data obtained from additional research related to the premovement and horizontal movement of participants with physical‐, cognitive‐, or age‐related disabilities. The aim is to provide an overview of currently available data sets related to, and key factors affecting the egress performance of, mixed ability populations which could be used to guide fire safety engineering decisions in the context of building design. 相似文献
7.
This paper presents an integrated passive damping approach in hybrid metal-CFRP parts for structural applications. In this concept a viscoelastic material is embedded in the joint zone of the hybrid component. To examine the connection strength single-lap-joint specimens were produced and tested and the influence of the used material combinations, different surface structures, and different process parameters i.e. the moment of cross-linking were evaluated. Afterwards, the metal-CFRP hybrids were tested in quasi-static tests to assess their connection strength and failure behaviour. Dynamic cyclic tensile tests with step-wise increased loading conditions were performed to determine the specimens damping behaviour and to estimate their fatigue performance. Finally, these results are compared to a state of the art metal-CFRP hybrid with rivets connecting both materials. 相似文献
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9.
Pavel Strunz Debashis Mukherji Přemysl Beran Ralph Gilles Lukas Karge Michael Hofmann Markus Hoelzel Joachim Rösler Gergely Farkas 《Metals and Materials International》2018,24(5):934-944
An addition of boron largely increases the ductility in polycrystalline high-temperature Co–Re alloys. Therefore, the effect of boron on the alloy structural characteristics is of high importance for the stability of the matrix at operational temperatures. Volume fractions of ε (hexagonal close-packed—hcp), γ (face-centered cubic—fcc) and σ (Cr2Re3 type) phases were measured at ambient and high temperatures (up to 1500 °C) for a boron-containing Co–17Re–23Cr alloy using neutron diffraction. The matrix phase undergoes an allotropic transformation from ε to γ structure at high temperatures, similar to pure cobalt and to the previously investigated, more complex Co–17Re–23Cr–1.2Ta–2.6C alloy. It was determined in this study that the transformation temperature depends on the boron content (0–1000 wt. ppm). Nevertheless, the transformation temperature did not change monotonically with the increase in the boron content but reached a minimum at approximately 200 ppm of boron. A probable reason is the interplay between the amount of boron in the matrix and the amount of σ phase, which binds hcp-stabilizing elements (Cr and Re). Moreover, borides were identified in alloys with high boron content. 相似文献
10.
Alice Maurer Prof. Dr. Florian P. Seebeck 《Chembiochem : a European journal of chemical biology》2020,21(20):2908-2911
Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD. 相似文献