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Svetlana Kalinina; Benedikt Cramer; Hans-Ulrich Humpf. Current and future perspectives of mycotoxin research — report from the 42nd Mycotoxin Workshop (Online conference). Mycotoxin Research 2021, 1 -4.
AMA StyleSvetlana Kalinina, Benedikt Cramer, Hans-Ulrich Humpf. Current and future perspectives of mycotoxin research — report from the 42nd Mycotoxin Workshop (Online conference). Mycotoxin Research. 2021; ():1-4.
Chicago/Turabian StyleSvetlana Kalinina; Benedikt Cramer; Hans-Ulrich Humpf. 2021. "Current and future perspectives of mycotoxin research — report from the 42nd Mycotoxin Workshop (Online conference)." Mycotoxin Research , no. : 1-4.
Tubular epithelial cells of the human kidney are considered as targets of Shiga toxins (Stxs) in the Stx-mediated pathogenesis of hemolytic–uremic syndrome (HUS) caused by Stx-releasing enterohemorrhagic Escherichia coli (EHEC). Analysis of Stx-binding glycosphingolipids (GSLs) of primary human renal proximal tubular epithelial cells (pHRPTEpiCs) yielded globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) with Cer (d18:1, C16:0), Cer (d18:1, C22:0), and Cer (d18:1, C24:1/C24:0) as the dominant lipoforms. Investigation of detergent-resistant membranes (DRMs) and nonDRMs, serving as equivalents for the liquid-ordered and liquid-disordered membrane phase, respectively, revealed the prevalence of Gb3Cer and Gb4Cer together with cholesterol and sphingomyelin in DRMs, suggesting lipid raft association. Stx1a and Stx2a exerted strong cellular damage with half-maximal cytotoxic doses (CD50) of 1.31 × 102 pg/mL and 1.66 × 103 pg/mL, respectively, indicating one order of magnitude higher cellular cytotoxicity of Stx1a. Surface acoustic wave (SAW) real-time interaction analysis using biosensor surfaces coated with DRM or nonDRM fractions gave stronger binding capability of Stx1a versus Stx2a that correlated with the lower cytotoxicity of Stx2a. Our study underlines the substantial role of proximal tubular epithelial cells of the human kidney being associated with the development of Stx-mediated HUS at least for Stx1a, while the impact of Stx2a remains somewhat ambiguous.
Johanna Detzner; Anna-Lena Klein; Gottfried Pohlentz; Elisabeth Krojnewski; Hans-Ulrich Humpf; Alexander Mellmann; Helge Karch; Johannes Müthing. Primary Human Renal Proximal Tubular Epithelial Cells (pHRPTEpiCs): Shiga Toxin (Stx) Glycosphingolipid Receptors, Stx Susceptibility, and Interaction with Membrane Microdomains. Toxins 2021, 13, 529 .
AMA StyleJohanna Detzner, Anna-Lena Klein, Gottfried Pohlentz, Elisabeth Krojnewski, Hans-Ulrich Humpf, Alexander Mellmann, Helge Karch, Johannes Müthing. Primary Human Renal Proximal Tubular Epithelial Cells (pHRPTEpiCs): Shiga Toxin (Stx) Glycosphingolipid Receptors, Stx Susceptibility, and Interaction with Membrane Microdomains. Toxins. 2021; 13 (8):529.
Chicago/Turabian StyleJohanna Detzner; Anna-Lena Klein; Gottfried Pohlentz; Elisabeth Krojnewski; Hans-Ulrich Humpf; Alexander Mellmann; Helge Karch; Johannes Müthing. 2021. "Primary Human Renal Proximal Tubular Epithelial Cells (pHRPTEpiCs): Shiga Toxin (Stx) Glycosphingolipid Receptors, Stx Susceptibility, and Interaction with Membrane Microdomains." Toxins 13, no. 8: 529.
A large number of secondary metabolites have been isolated from the filamentous fungus Stachybotrys chartarum and have been described before. Fourteen of these natural compounds were evaluated in vitro in the present study for their inhibitory activity towards the cancer target CK2. Among these compounds, stachybotrychromene C, stachybotrydial acetate and acetoxystachybotrydial acetate turned out to be potent inhibitors with IC50 values of 0.32 µM, 0.69 µM and 1.86 µM, respectively. The effects of these three compounds on cell proliferation, growth and viability of MCF7 cells, representing human breast adenocarcinoma as well as A427 (human lung carcinoma) and A431 (human epidermoid carcinoma) cells, were tested using EdU assay, IncuCyte® live-cell imaging and MTT assay. The most active compound in inhibiting MCF7 cell proliferation was acetoxystachybotrydial acetate with an EC50 value of 0.39 µM. In addition, acetoxystachybotrydial acetate turned out to inhibit the growth of all three cell lines completely at a concentration of 1 µM. In contrast, cell viability was impaired only moderately, to 37%, 14% and 23% in MCF7, A427 and A431 cells, respectively.
Samer Haidar; Franziska Jürgens; Dagmar Aichele; Annika Jagels; Hans-Ulrich Humpf; Joachim Jose. Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2. Molecules 2021, 26, 4453 .
AMA StyleSamer Haidar, Franziska Jürgens, Dagmar Aichele, Annika Jagels, Hans-Ulrich Humpf, Joachim Jose. Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2. Molecules. 2021; 26 (15):4453.
Chicago/Turabian StyleSamer Haidar; Franziska Jürgens; Dagmar Aichele; Annika Jagels; Hans-Ulrich Humpf; Joachim Jose. 2021. "Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2." Molecules 26, no. 15: 4453.
Molecular networking connects mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. As a result, the fragmentation spectra of these ion species often remain unconnected in tandem mass spectrometry-based molecular networks, leading to redundant and disconnected sub-networks of the same compound classes. To overcome this bottleneck, we develop Ion Identity Molecular Networking (IIMN) that integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule. The new feature relationships improve network connectivity for structurally related molecules, can be used to reveal unknown ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral reference libraries. IIMN is integrated into various open source feature finding tools and the GNPS environment. Moreover, IIMN-based spectral libraries with a broad coverage of ion species are publicly available.
Robin Schmid; Daniel Petras; Louis-Félix Nothias; Mingxun Wang; Allegra T. Aron; Annika Jagels; Hiroshi Tsugawa; Johannes Rainer; Mar Garcia-Aloy; Kai Dührkop; Ansgar Korf; Tomáš Pluskal; Zdeněk Kameník; Alan K. Jarmusch; Andrés Mauricio Caraballo-Rodríguez; Kelly C. Weldon; Melissa Nothias-Esposito; Alexander A. Aksenov; Anelize Bauermeister; Andrea Albarracin Orio; Carlismari O. Grundmann; Fernando Vargas; Irina Koester; Julia M. Gauglitz; Emily C. Gentry; Yannick Hövelmann; Svetlana A. Kalinina; Matthew A. Pendergraft; Morgan Panitchpakdi; Richard Tehan; Audrey Le Gouellec; Gajender Aleti; Helena Mannochio Russo; Birgit Arndt; Florian Hübner; Heiko Hayen; Hui Zhi; Manuela Raffatellu; Kimberly A. Prather; Lihini I. Aluwihare; Sebastian Böcker; Kerry L. McPhail; Hans-Ulrich Humpf; Uwe Karst; Pieter C. Dorrestein. Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment. Nature Communications 2021, 12, 1 -12.
AMA StyleRobin Schmid, Daniel Petras, Louis-Félix Nothias, Mingxun Wang, Allegra T. Aron, Annika Jagels, Hiroshi Tsugawa, Johannes Rainer, Mar Garcia-Aloy, Kai Dührkop, Ansgar Korf, Tomáš Pluskal, Zdeněk Kameník, Alan K. Jarmusch, Andrés Mauricio Caraballo-Rodríguez, Kelly C. Weldon, Melissa Nothias-Esposito, Alexander A. Aksenov, Anelize Bauermeister, Andrea Albarracin Orio, Carlismari O. Grundmann, Fernando Vargas, Irina Koester, Julia M. Gauglitz, Emily C. Gentry, Yannick Hövelmann, Svetlana A. Kalinina, Matthew A. Pendergraft, Morgan Panitchpakdi, Richard Tehan, Audrey Le Gouellec, Gajender Aleti, Helena Mannochio Russo, Birgit Arndt, Florian Hübner, Heiko Hayen, Hui Zhi, Manuela Raffatellu, Kimberly A. Prather, Lihini I. Aluwihare, Sebastian Böcker, Kerry L. McPhail, Hans-Ulrich Humpf, Uwe Karst, Pieter C. Dorrestein. Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment. Nature Communications. 2021; 12 (1):1-12.
Chicago/Turabian StyleRobin Schmid; Daniel Petras; Louis-Félix Nothias; Mingxun Wang; Allegra T. Aron; Annika Jagels; Hiroshi Tsugawa; Johannes Rainer; Mar Garcia-Aloy; Kai Dührkop; Ansgar Korf; Tomáš Pluskal; Zdeněk Kameník; Alan K. Jarmusch; Andrés Mauricio Caraballo-Rodríguez; Kelly C. Weldon; Melissa Nothias-Esposito; Alexander A. Aksenov; Anelize Bauermeister; Andrea Albarracin Orio; Carlismari O. Grundmann; Fernando Vargas; Irina Koester; Julia M. Gauglitz; Emily C. Gentry; Yannick Hövelmann; Svetlana A. Kalinina; Matthew A. Pendergraft; Morgan Panitchpakdi; Richard Tehan; Audrey Le Gouellec; Gajender Aleti; Helena Mannochio Russo; Birgit Arndt; Florian Hübner; Heiko Hayen; Hui Zhi; Manuela Raffatellu; Kimberly A. Prather; Lihini I. Aluwihare; Sebastian Böcker; Kerry L. McPhail; Hans-Ulrich Humpf; Uwe Karst; Pieter C. Dorrestein. 2021. "Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment." Nature Communications 12, no. 1: 1-12.
This study presents a comprehensive two-dimensional gas chromatography with negative chemical ionization quadrupole time-of-flight mass spectrometry (GC × GC–NCI–QTOF/MS) method, which allows for a precise chromatographic separation of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs). A new reversed-phase column setup was used, which allows for more accurate separation of MCCPs compared to known GC × GC methods. In a pilot study, 25 freshwater fish samples were analyzed with this method to characterize chlorinated paraffin (CP) compositions. The CP composition was similar in the samples, an observation that is important for the development of a suitable routine method. MCCP contamination was considerably higher than SCCP contamination, with concentrations of 1.3–410 ng/g of wet weight and 0.67–6.5 ng/g of wet weight, respectively. These results were compared to those obtained using a second method, direct injection–atmospheric pressure chemical ionization (APCI)–Orbitrap/mass spectrometry (MS). GC × GC separation was considered to be advantageous for accurate quantification of CP contamination.
Rebekka Tien; Thorsten Bernsmann; Hans-Ulrich Humpf; Peter Fürst. Structural Identification and Quantification of Chlorinated Paraffins in Fish Samples Using Comprehensive Two-Dimensional Gas Chromatography with Negative Chemical Ionization Quadrupole Time-of-Flight Mass Spectrometry and Comparison to a Direct Injection–Atmospheric Pressure Chemical Ionization–Orbitrap/Mass Spectrometry Method. Journal of Agricultural and Food Chemistry 2021, 69, 7158 -7167.
AMA StyleRebekka Tien, Thorsten Bernsmann, Hans-Ulrich Humpf, Peter Fürst. Structural Identification and Quantification of Chlorinated Paraffins in Fish Samples Using Comprehensive Two-Dimensional Gas Chromatography with Negative Chemical Ionization Quadrupole Time-of-Flight Mass Spectrometry and Comparison to a Direct Injection–Atmospheric Pressure Chemical Ionization–Orbitrap/Mass Spectrometry Method. Journal of Agricultural and Food Chemistry. 2021; 69 (25):7158-7167.
Chicago/Turabian StyleRebekka Tien; Thorsten Bernsmann; Hans-Ulrich Humpf; Peter Fürst. 2021. "Structural Identification and Quantification of Chlorinated Paraffins in Fish Samples Using Comprehensive Two-Dimensional Gas Chromatography with Negative Chemical Ionization Quadrupole Time-of-Flight Mass Spectrometry and Comparison to a Direct Injection–Atmospheric Pressure Chemical Ionization–Orbitrap/Mass Spectrometry Method." Journal of Agricultural and Food Chemistry 69, no. 25: 7158-7167.
In the course of assessing the human exposure to mycotoxins, biomarker-based approaches have proven to be important tools. Low concentration levels, complex matrix compositions, structurally diverse analytes, and the large size of sample cohorts are the main challenges of analytical procedures. For that reason, an online solid phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry (online SPE-UHPLC-MS/MS) method was developed, allowing for the sensitive, robust, and rapid analysis of 11 relevant mycotoxins and mycotoxin metabolites in human urine. The included spectrum of analytes comprises aflatoxin M1 (AFM1), altenuene (ALT), alternariol monomethyl ether (AME), alternariol (AOH), citrinin (CIT) and its metabolite dihydrocitrinone (DH-CIT), fumonisin B1 (FB1), ochratoxin A (OTA), and zearalenone (ZEN) as well as α- and β-zearalenol (α- and β-ZEL). Reliable quantitation was achieved by means of stable isotope dilution, except for ALT, AME and AOH using matrix calibrations. The evaluation of method performance displayed low limits of detection in the range of pg/mL urine, satisfactory apparent recovery rates as well as high accuracy and precision during intra- and interday repeatability. Within the analysis of Zimbabwean urine samples (n = 50), the applicability of the newly developed method was shown. In addition to FB1 being quantifiable in all analyzed samples, six other mycotoxin biomarkers were detected. Compared to the occurrence rates obtained after analyzing the same sample set using an established dilute and shoot (DaS) approach, a considerably higher number of positive samples was observed when applying the online SPE method. Owing to the increased sensitivity, less need of sample handling, and low time effort, the herein presented online SPE approach provides a valuable contribution to human biomonitoring of mycotoxin exposure.
Jessica Schmidt; Benedikt Cramer; Paul Turner; Rebecca Stoltzfus; Jean Humphrey; Laura Smith; Hans-Ulrich Humpf. Determination of Urinary Mycotoxin Biomarkers Using a Sensitive Online Solid Phase Extraction-UHPLC-MS/MS Method. Toxins 2021, 13, 418 .
AMA StyleJessica Schmidt, Benedikt Cramer, Paul Turner, Rebecca Stoltzfus, Jean Humphrey, Laura Smith, Hans-Ulrich Humpf. Determination of Urinary Mycotoxin Biomarkers Using a Sensitive Online Solid Phase Extraction-UHPLC-MS/MS Method. Toxins. 2021; 13 (6):418.
Chicago/Turabian StyleJessica Schmidt; Benedikt Cramer; Paul Turner; Rebecca Stoltzfus; Jean Humphrey; Laura Smith; Hans-Ulrich Humpf. 2021. "Determination of Urinary Mycotoxin Biomarkers Using a Sensitive Online Solid Phase Extraction-UHPLC-MS/MS Method." Toxins 13, no. 6: 418.
Recent studies have implied that environmental toxins, such as mycotoxins, are risk factors for neurodegenerative diseases. To act directly as neurotoxins, mycotoxins need to penetrate or affect the integrity of the blood-brain barrier, which protects the mammalian brain from potentially harmful substances. As common food and feed contaminants of fungal origin, the interest in the potential neurotoxicity of ochratoxin A, citrinin and their metabolites has recently increased. Primary porcine brain capillary endothelial cells were used to investigate cytotoxic or barrier-weakening effects of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone. The transfer and transport properties of the mycotoxins across the barrier formed by porcine brain capillary endothelial cell monolayers were analysed using HPLC-MS/MS. High levels of Ochratoxin A caused cytotoxic and barrier-weakening effects, whereas ochratoxin α, citrinin and dihydrocitrinone showed no adverse effects up to 10 µM. Likely due to efflux transporter proteins, the transfer to the brain compartment was much slower than expected from their high lipophilicity. Due to their slow transfer across the blood-brain barrier, cerebral exposure of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone is low and neurotoxicity is likely to play a subordinate role in their toxicity at common physiological concentrations.
Matthias Behrens; Sabine Hüwel; Hans-Joachim Galla; Hans-Ulrich Humpf. Efflux at the Blood-Brain Barrier Reduces the Cerebral Exposure to Ochratoxin A, Ochratoxin α, Citrinin and Dihydrocitrinone. Toxins 2021, 13, 327 .
AMA StyleMatthias Behrens, Sabine Hüwel, Hans-Joachim Galla, Hans-Ulrich Humpf. Efflux at the Blood-Brain Barrier Reduces the Cerebral Exposure to Ochratoxin A, Ochratoxin α, Citrinin and Dihydrocitrinone. Toxins. 2021; 13 (5):327.
Chicago/Turabian StyleMatthias Behrens; Sabine Hüwel; Hans-Joachim Galla; Hans-Ulrich Humpf. 2021. "Efflux at the Blood-Brain Barrier Reduces the Cerebral Exposure to Ochratoxin A, Ochratoxin α, Citrinin and Dihydrocitrinone." Toxins 13, no. 5: 327.
1,3-Dioxanes 1 and cyclohexanes 2 bearing a phenyl ring and an aminoethyl moiety in 1,3-relationship to each other represent highly potent σ1 receptor antagonists. In order to increase the chemical stability of the acetalic 1,3-dioxanes 1 and the polarity of the cyclohexanes 2, tetrahydropyran derivatives 3 equipped with the same substituents were designed, synthesized and pharmacologically evaluated. The key step of the synthesis was a lipase-catalyzed enantioselective acetylation of the alcohol (R)-5 leading finally to enantiomerically pure test compounds 3a-g. With respect to σ1 receptor affinity and selectivity over a broad range of related (σ2, PCP binding site) and further targets, the enantiomeric benzylamines 3a and cyclohexylmethylamines 3b represent the most promising drug candidates of this series. However, the eudismic ratio for σ1 binding is only in the range of 2.5–3.3. Classical molecular dynamics (MD) simulations confirmed the same binding pose for both the tetrahydropyran 3 and cyclohexane derivatives 2 at the σ1 receptor, according to which: i) the protonated amino moiety of (2S,6R)-3a engages the same key polar interactions with Glu172 (ionic) and Phe107 (π-cation), ii) the lipophilic parts of (2S,6R)-3a are hosted in three hydrophobic regions of the σ1 receptor, and iii) the O-atom of the tetrahydropyran derivatives 3 does not show a relevant interaction with the σ1 receptor. Further in silico evidences obtained by the application of free energy perturbation and steered MD techniques fully supported the experimentally observed difference in receptor/ligand affinities. Tetrahydropyrans 3 require a lower dissociative force peak than cyclohexane analogs 2. Enantiomeric benzylamines 3a and cyclohexylmethylamines 3b were able to inhibit the growth of the androgen negative human prostate cancer cell line DU145. The cyclohexylmethylamine (2S,6R)-3b showed the highest σ1 affinity (Ki(σ1) = 0.95 nM) and the highest analgesic activity in vivo (67%).
Nicole Kopp; Gianluca Civenni; Domenico Marson; Erik Laurini; Sabrina Pricl; Carlo V. Catapano; Hans-Ulrich Humpf; Carmen Almansa; Francisco Rafael Nieto; Dirk Schepmann; Bernhard Wünsch. Chemoenzymatic synthesis of 2,6-disubstituted tetrahydropyrans with high σ1 receptor affinity, antitumor and analgesic activity. European Journal of Medicinal Chemistry 2021, 219, 113443 .
AMA StyleNicole Kopp, Gianluca Civenni, Domenico Marson, Erik Laurini, Sabrina Pricl, Carlo V. Catapano, Hans-Ulrich Humpf, Carmen Almansa, Francisco Rafael Nieto, Dirk Schepmann, Bernhard Wünsch. Chemoenzymatic synthesis of 2,6-disubstituted tetrahydropyrans with high σ1 receptor affinity, antitumor and analgesic activity. European Journal of Medicinal Chemistry. 2021; 219 ():113443.
Chicago/Turabian StyleNicole Kopp; Gianluca Civenni; Domenico Marson; Erik Laurini; Sabrina Pricl; Carlo V. Catapano; Hans-Ulrich Humpf; Carmen Almansa; Francisco Rafael Nieto; Dirk Schepmann; Bernhard Wünsch. 2021. "Chemoenzymatic synthesis of 2,6-disubstituted tetrahydropyrans with high σ1 receptor affinity, antitumor and analgesic activity." European Journal of Medicinal Chemistry 219, no. : 113443.
M. Hahn; M. Behrens; H.‐U. Humpf. Kann Bier glücklich machen? Studien zum Transport des Bierinhaltsstoffs Hordenin über zelluläre Barrieren. Lebensmittelchemie 2021, 75, S1-033 -S1-033.
AMA StyleM. Hahn, M. Behrens, H.‐U. Humpf. Kann Bier glücklich machen? Studien zum Transport des Bierinhaltsstoffs Hordenin über zelluläre Barrieren. Lebensmittelchemie. 2021; 75 (S1):S1-033-S1-033.
Chicago/Turabian StyleM. Hahn; M. Behrens; H.‐U. Humpf. 2021. "Kann Bier glücklich machen? Studien zum Transport des Bierinhaltsstoffs Hordenin über zelluläre Barrieren." Lebensmittelchemie 75, no. S1: S1-033-S1-033.
M. Kasimir; I. Westkamp; M. Behrens; H.‐U. Humpf. Das Schweine‐Caecum‐Modell ‐ Ein wertvolles Werkzeug zur Untersuchung des intestinalen Metabolismus von Lebensmittelinhaltsstoffen. Lebensmittelchemie 2021, 75, S1-035 -S1-036.
AMA StyleM. Kasimir, I. Westkamp, M. Behrens, H.‐U. Humpf. Das Schweine‐Caecum‐Modell ‐ Ein wertvolles Werkzeug zur Untersuchung des intestinalen Metabolismus von Lebensmittelinhaltsstoffen. Lebensmittelchemie. 2021; 75 (S1):S1-035-S1-036.
Chicago/Turabian StyleM. Kasimir; I. Westkamp; M. Behrens; H.‐U. Humpf. 2021. "Das Schweine‐Caecum‐Modell ‐ Ein wertvolles Werkzeug zur Untersuchung des intestinalen Metabolismus von Lebensmittelinhaltsstoffen." Lebensmittelchemie 75, no. S1: S1-035-S1-036.
A simple and effective approach for HPLC-MS/MS based multi-mycotoxin analysis in human urine samples was developed by application of dried urine spots (DUS) as alternative on-site sampling strategy. The newly developed method enables the detection and quantitation of 14 relevant mycotoxins and mycotoxin metabolites, including citrinin (CIT), dihydrocitrinone (DH-CIT), deoxynivalenol (DON), fumonisin B1 (FB1), T-2 Toxin (T-2), HT-2 Toxin (HT-2), ochratoxin A (OTA), 2′R-ochratoxin A (2′R-OTA), ochratoxin α (OTα), tenuazonic acid and allo-tenuazonic acid (TeA + allo-TeA), zearalenone (ZEN), zearalanone (ZAN), α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL). Besides the spotting procedure, sample preparation includes enzymatic cleavage of glucuronic acid conjugates and stable isotope dilution analysis. Method validation revealed low limits of detection in the range of pg/mL urine and excellent apparent recovery rates for most analytes. Stability investigation of DUS displayed no or only slight decrease of the analyte concentration over a period of 28 days at room temperature. The new method was applied to the analysis of a set of urine samples (n = 91) from a Swedish cohort. The four analytes, DH-CIT, DON, OTA, and TeA + allo-TeA, could be detected and quantified in amounts ranging from 0.06 to 0.97 ng/mL, 3.03 to 136 ng/mL, 0.013 to 0.434 ng/mL and from 0.36 to 47 ng/mL in 38.5%, 70.3%, 68.1%, and 94.5% of the samples, respectively. Additional analysis of these urine samples with an established dilute and shoot (DaS) approach displayed a high consistency of the results obtained with both methods. However, due to higher sensitivity, a larger number of positive samples were observed using the DUS method consequently providing a suitable approach for human biomonitoring of mycotoxin exposure.
Jessica Schmidt; Viktoria Lindemann; Monica Olsen; Benedikt Cramer; Hans-Ulrich Humpf. Dried urine spots as sampling technique for multi-mycotoxin analysis in human urine. Mycotoxin Research 2021, 37, 129 -140.
AMA StyleJessica Schmidt, Viktoria Lindemann, Monica Olsen, Benedikt Cramer, Hans-Ulrich Humpf. Dried urine spots as sampling technique for multi-mycotoxin analysis in human urine. Mycotoxin Research. 2021; 37 (2):129-140.
Chicago/Turabian StyleJessica Schmidt; Viktoria Lindemann; Monica Olsen; Benedikt Cramer; Hans-Ulrich Humpf. 2021. "Dried urine spots as sampling technique for multi-mycotoxin analysis in human urine." Mycotoxin Research 37, no. 2: 129-140.
Human kidney epithelial cells are supposed to be directly involved in the pathogenesis of the hemolytic–uremic syndrome (HUS) caused by Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli (EHEC). The characterization of the major and minor Stx-binding glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), respectively, of primary human renal cortical epithelial cells (pHRCEpiCs) revealed GSLs with Cer (d18:1, C16:0), Cer (d18:1, C22:0), and Cer (d18:1, C24:1/C24:0) as the dominant lipoforms. Using detergent-resistant membranes (DRMs) and non-DRMs, Gb3Cer and Gb4Cer prevailed in the DRM fractions, suggesting their association with microdomains in the liquid-ordered membrane phase. A preference of Gb3Cer and Gb4Cer endowed with C24:0 fatty acid accompanied by minor monounsaturated C24:1-harboring counterparts was observed in DRMs, whereas the C24:1 fatty acid increased in relation to the saturated equivalents in non-DRMs. A shift of the dominant phospholipid phosphatidylcholine with saturated fatty acids in the DRM to unsaturated species in the non-DRM fractions correlated with the GSL distribution. Cytotoxicity assays gave a moderate susceptibility of pHRCEpiCs to the Stx1a and Stx2a subtypes when compared to highly sensitive Vero-B4 cells. The results indicate that presence of Stx-binding GSLs per se and preferred occurrence in microdomains do not necessarily lead to a high cellular susceptibility towards Stx.
Johanna Detzner; Elisabeth Krojnewski; Gottfried Pohlentz; Daniel Steil; Hans-Ulrich Humpf; Alexander Mellmann; Helge Karch; Johannes Müthing. Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity. Toxins 2021, 13, 139 .
AMA StyleJohanna Detzner, Elisabeth Krojnewski, Gottfried Pohlentz, Daniel Steil, Hans-Ulrich Humpf, Alexander Mellmann, Helge Karch, Johannes Müthing. Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity. Toxins. 2021; 13 (2):139.
Chicago/Turabian StyleJohanna Detzner; Elisabeth Krojnewski; Gottfried Pohlentz; Daniel Steil; Hans-Ulrich Humpf; Alexander Mellmann; Helge Karch; Johannes Müthing. 2021. "Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity." Toxins 13, no. 2: 139.
Plants from the Solanaceae family are known to be sources of several nutritionally relevant steroidal glycoalkaloids (SGAs). With the aim of quantitatively investigating the occurrence of the main SGA from tomatoes, eggplants, and potatoes in various food samples and evaluating their relevance in the human diet, a rapid single-step extraction liquid chromatography–tandem mass spectrometry method was developed. Over the course of isolating several commercially unavailable SGAs from tomato products to use them as reference standards, a previously unknown derivative was detected, structurally characterized, and identified as a novel isomer of esculeoside B-1 and B-2. After validation of the method, 36 food items exclusively derived from Solanaceae plants were analyzed for their SGA contents and a specific occurrence of each alkaloid in tomato, eggplant, or potato products was revealed. This is the first study reporting quantitative data on the occurrence of esculeoside A, B-1, B-2, and iso-esculeoside B in tomato products obtained by using appropriate reference compounds rather than applying a semi-quantitative approach based on α-tomatine as a reference. Some of the analyzed tomato products contained the esculeosides in concentrations of >500 mg/kg, clearly indicating their relevance in the human diet and the need of investigating their potential bioactivities in the future.
Katharina Steinert; Yannick Hövelmann; Florian Hübner; Hans-Ulrich Humpf. Identification of Novel Iso-Esculeoside B from Tomato Fruits and LC–MS/MS-Based Food Screening for Major Dietary Steroidal Alkaloids Focused on Esculeosides. Journal of Agricultural and Food Chemistry 2020, 68, 14492 -14501.
AMA StyleKatharina Steinert, Yannick Hövelmann, Florian Hübner, Hans-Ulrich Humpf. Identification of Novel Iso-Esculeoside B from Tomato Fruits and LC–MS/MS-Based Food Screening for Major Dietary Steroidal Alkaloids Focused on Esculeosides. Journal of Agricultural and Food Chemistry. 2020; 68 (49):14492-14501.
Chicago/Turabian StyleKatharina Steinert; Yannick Hövelmann; Florian Hübner; Hans-Ulrich Humpf. 2020. "Identification of Novel Iso-Esculeoside B from Tomato Fruits and LC–MS/MS-Based Food Screening for Major Dietary Steroidal Alkaloids Focused on Esculeosides." Journal of Agricultural and Food Chemistry 68, no. 49: 14492-14501.
Scope As orange juice belongs to one of the most consumed juices worldwide, a human study was performed to identify urinary biomarkers for the consumption of orange juice in order to differentiate between low, medium and high intake. Methods and Results The 32 study participants abstained from citrus fruits, juices and products thereof, except for one portion of orange juice, for eight days. Throughout the study, spot urine samples were collected and quantitatively analyzed by HPLC‐MS/MS regarding their content of several potential biomarkers for orange juice intake after enzymatic treatment with β‐glucuronidase. Proline betaine was determined as a long‐term biomarker: based on its urinary excretion, orange juice consumption is traceable for at least 72 h after intake. Naringenin and hesperetin were identified as qualitative short‐term biomarkers. Synephrine sulfate also showed a fast increase and decrease in a semi‐quantitative approach. In the case of phloretin, no correlation between orange juice consumption and the urinary concentration was observed. Conclusion Proline betaine is the most promising biomarker for orange juice consumption and allows to differentiate between low, medium and high intake. Hesperetin and naringenin (as well as synephrine) are applicable as supporting biomarkers, whereas phloretin does not represent a reliable biomarker for orange juice consumption. This article is protected by copyright. All rights reserved
Theresa Saenger; Florian Hübner; Viktoria Lindemann; Kristina Ganswind; Hans‐Ulrich Humpf. Urinary Biomarkers for Orange Juice Consumption. Molecular Nutrition & Food Research 2020, 65, e2000781 .
AMA StyleTheresa Saenger, Florian Hübner, Viktoria Lindemann, Kristina Ganswind, Hans‐Ulrich Humpf. Urinary Biomarkers for Orange Juice Consumption. Molecular Nutrition & Food Research. 2020; 65 (2):e2000781.
Chicago/Turabian StyleTheresa Saenger; Florian Hübner; Viktoria Lindemann; Kristina Ganswind; Hans‐Ulrich Humpf. 2020. "Urinary Biomarkers for Orange Juice Consumption." Molecular Nutrition & Food Research 65, no. 2: e2000781.
Claviceps purpurea is a plant pathogenic fungus which is still highly relevant in modern agriculture as it infects grasses such as rye and wheat. The disease caused by the consumption of contaminated grain or flour has been known since the Middle Ages and is termed ergotism. The main cause for the toxicity of this fungus is attributed to the ergot alkaloids. Apart from these alkaloids and the ergochromes known as ergot pigments, the secondary metabolism of C. purpurea is not well investigated. This study demonstrated the function of the polyketide synthase PKS7 in C. purpurea by determining the effect of its overexpression on metabolite profiles. For the first time, the depsides lecanoric acid, ethyl lecanorate, gerfelin, and C10-deoxy gerfelin were discovered as secondary metabolites of C. purpurea. Additionally, to estimate the contribution of isolated secondary metabolites to the toxic effects of C. purpurea, lecanoric acid, ethyl lecanorate, and orsellinic acid were tested on HepG2 and CCF-STTG1 cell lines. This study provides the first report on the function of C. purpurea PKS7 responsible for the production of depsides, among which lecanoric acid and ethyl lecanorate were identified as main secondary metabolites.
Friederike Lünne; Eva-Maria Niehaus; Sarah Lipinski; Jonas Kunigkeit; Svetlana A. Kalinina; Hans-Ulrich Humpf. Identification of the polyketide synthase PKS7 responsible for the production of lecanoric acid and ethyl lecanorate in Claviceps purpurea. Fungal Genetics and Biology 2020, 145, 103481 .
AMA StyleFriederike Lünne, Eva-Maria Niehaus, Sarah Lipinski, Jonas Kunigkeit, Svetlana A. Kalinina, Hans-Ulrich Humpf. Identification of the polyketide synthase PKS7 responsible for the production of lecanoric acid and ethyl lecanorate in Claviceps purpurea. Fungal Genetics and Biology. 2020; 145 ():103481.
Chicago/Turabian StyleFriederike Lünne; Eva-Maria Niehaus; Sarah Lipinski; Jonas Kunigkeit; Svetlana A. Kalinina; Hans-Ulrich Humpf. 2020. "Identification of the polyketide synthase PKS7 responsible for the production of lecanoric acid and ethyl lecanorate in Claviceps purpurea." Fungal Genetics and Biology 145, no. : 103481.
We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i, a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound 21m with 27 nM inhibitory activity toward thrombin. For the first time, acylated 1,2,4-triazol-5-amines were proved to have anticoagulant properties and the ability to affect thrombin- and cancer-cell-induced platelet aggregation. Performed mass spectrometric analysis and molecular modeling allowed us to discover previously unknown interactions between the synthesized inhibitors and the active site of FXIIa, which uncovered the mechanistic details of FXIIa inhibition. Synthesized compounds represent a promising starting point for the development of novel antithrombotic drugs or chemical tools for studying the role of FXIIa and thrombin in physiological and pathological processes.
Marvin Korff; Lukas Imberg; Jonas M. Will; Nico Bückreiß; Svetlana A. Kalinina; Benjamin M. Wenzel; Gregor A. Kastner; Constantin G. Daniliuc; Maximilian Barth; Ruzanna A. Ovsepyan; Kirill R. Butov; Hans-Ulrich Humpf; Matthias Lehr; Mikhail A. Panteleev; Antti Poso; Uwe Karst; Torsten Steinmetzer; Gerd Bendas; Dmitrii V. Kalinin. Acylated 1H-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action. Journal of Medicinal Chemistry 2020, 63, 13159 -13186.
AMA StyleMarvin Korff, Lukas Imberg, Jonas M. Will, Nico Bückreiß, Svetlana A. Kalinina, Benjamin M. Wenzel, Gregor A. Kastner, Constantin G. Daniliuc, Maximilian Barth, Ruzanna A. Ovsepyan, Kirill R. Butov, Hans-Ulrich Humpf, Matthias Lehr, Mikhail A. Panteleev, Antti Poso, Uwe Karst, Torsten Steinmetzer, Gerd Bendas, Dmitrii V. Kalinin. Acylated 1H-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action. Journal of Medicinal Chemistry. 2020; 63 (21):13159-13186.
Chicago/Turabian StyleMarvin Korff; Lukas Imberg; Jonas M. Will; Nico Bückreiß; Svetlana A. Kalinina; Benjamin M. Wenzel; Gregor A. Kastner; Constantin G. Daniliuc; Maximilian Barth; Ruzanna A. Ovsepyan; Kirill R. Butov; Hans-Ulrich Humpf; Matthias Lehr; Mikhail A. Panteleev; Antti Poso; Uwe Karst; Torsten Steinmetzer; Gerd Bendas; Dmitrii V. Kalinin. 2020. "Acylated 1H-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action." Journal of Medicinal Chemistry 63, no. 21: 13159-13186.
Kristin Busse; Ingo Ebner; Hans-Ulrich Humpf; Natalia Ivleva; Andrea Kaeppler; Barbara E. Oßmann; Darena Schymanski. Comment on “Plastic Teabags Release Billions of Microparticles and Nanoparticles into Tea”. Environmental Science & Technology 2020, 54, 14134 -14135.
AMA StyleKristin Busse, Ingo Ebner, Hans-Ulrich Humpf, Natalia Ivleva, Andrea Kaeppler, Barbara E. Oßmann, Darena Schymanski. Comment on “Plastic Teabags Release Billions of Microparticles and Nanoparticles into Tea”. Environmental Science & Technology. 2020; 54 (21):14134-14135.
Chicago/Turabian StyleKristin Busse; Ingo Ebner; Hans-Ulrich Humpf; Natalia Ivleva; Andrea Kaeppler; Barbara E. Oßmann; Darena Schymanski. 2020. "Comment on “Plastic Teabags Release Billions of Microparticles and Nanoparticles into Tea”." Environmental Science & Technology 54, no. 21: 14134-14135.
In the past, it was generally accepted as a default assumption that No-Observed-Adverse-Effect Levels (NOAELs) or Lowest-Observed-Adverse-Effect Levels (LOAELs) in long-term toxicity studies are lower than in short-term ones, i.e. the toxic potency increases with prolonged exposure duration. Recent studies on pesticides and industrial chemicals reported that subacute, subchronic or chronic NOAELs/LOAELs are similar when study design factors are appropriately considered. We investigated whether these findings also apply to certain food constituents. After reviewing subchronic and chronic toxicity studies on more than 100 compounds, a total of 32 compounds could be included in the analysis. Geometric mean (GM) values of subchronic vs. chronic NOAEL or LOAEL ratios ranged from 1.0 to 2.0, with a geometric standard deviation from 2.2 to 4.2, which is consistent with data reported in the literature. While for many of the investigated compounds the ratio is around 1 – suggesting that health-based guidance values could appropriately be derived from subchronic toxicity studies – our study also identified some substances with higher ratios leading to a GM of around 2. The EFSA Scientific Committee suggested to apply an uncertainty factor of 2 to extrapolate from subchronic to chronic studies and, as a precautionary approach, we concur with this suggestion.
Sabine Guth; Angelika Roth; Barbara Engeli; Dirk W. Lachenmeier; Alexander T. Cartus; Stephanie Hüser; Matthias Baum; Patrick Diel; Gerhard Eisenbrand; Jan G. Hengstler; Hans-Ulrich Humpf; Hans-Georg Joost; Alfonso Lampen; Marcel Leist; Doris Marko; Pablo Steinberg; Angela Mally; Jürg A. Zarn. Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents. Food and Chemical Toxicology 2020, 146, 111784 .
AMA StyleSabine Guth, Angelika Roth, Barbara Engeli, Dirk W. Lachenmeier, Alexander T. Cartus, Stephanie Hüser, Matthias Baum, Patrick Diel, Gerhard Eisenbrand, Jan G. Hengstler, Hans-Ulrich Humpf, Hans-Georg Joost, Alfonso Lampen, Marcel Leist, Doris Marko, Pablo Steinberg, Angela Mally, Jürg A. Zarn. Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents. Food and Chemical Toxicology. 2020; 146 ():111784.
Chicago/Turabian StyleSabine Guth; Angelika Roth; Barbara Engeli; Dirk W. Lachenmeier; Alexander T. Cartus; Stephanie Hüser; Matthias Baum; Patrick Diel; Gerhard Eisenbrand; Jan G. Hengstler; Hans-Ulrich Humpf; Hans-Georg Joost; Alfonso Lampen; Marcel Leist; Doris Marko; Pablo Steinberg; Angela Mally; Jürg A. Zarn. 2020. "Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents." Food and Chemical Toxicology 146, no. : 111784.
The genus Stachybotrys belongs to filamentous fungi found in indoor environment, mostly on cellulose‐rich substrates after water‐damage. The major purpose of this study was to investigate the influence of different building materials in case of mold infestation on the mycotoxin production of Stachybotrys species. Fifteen Stachybotrys mycotoxins including satratoxins, phenylspirodrimanes, and recently discovered stachybotrychromenes were in the focus of the investigations. Artificial and natural infestations were compared to determine whether environmental factors, for example, time of growth, temperature, humidity, and material additives have an influence on the observed mycotoxin profiles. It turned out that mycotoxin profiles from Stachybotrys spp. on building materials can be influenced by cellulose, paints, and paste of the materials. The total toxin levels of artificially and naturally contaminated gypsum board samples ranged up to 30 µg/cm2, whereas wallpaper samples showed total toxin levels in the range of 20‐66 µg/cm2. A naturally infested sample disclosed the conversion of the dialdehyde components to the corresponding lactone isomers under the influence of light.
Annika Jagels; Felix Stephan; Simon Ernst; Viktoria Lindemann; Benedikt Cramer; Florian Hübner; Hans‐Ulrich Humpf. Artificial vs natural Stachybotrys infestation—Comparison of mycotoxin production on various building materials. Indoor Air 2020, 30, 1268 -1282.
AMA StyleAnnika Jagels, Felix Stephan, Simon Ernst, Viktoria Lindemann, Benedikt Cramer, Florian Hübner, Hans‐Ulrich Humpf. Artificial vs natural Stachybotrys infestation—Comparison of mycotoxin production on various building materials. Indoor Air. 2020; 30 (6):1268-1282.
Chicago/Turabian StyleAnnika Jagels; Felix Stephan; Simon Ernst; Viktoria Lindemann; Benedikt Cramer; Florian Hübner; Hans‐Ulrich Humpf. 2020. "Artificial vs natural Stachybotrys infestation—Comparison of mycotoxin production on various building materials." Indoor Air 30, no. 6: 1268-1282.
The Escherichia coli (E. coli) strains Nissle 1917 (EcN), 83972 and CFT073 are closely related but differ in their phenotypes and pathogenicity. The aim of this study was to compare the metabolome of these strains based on metabolomic data analysis of bacterial samples using liquid chromatography-high resolution mass spectrometry (LC-HRMS). The strains were cultivated in minimum essential medium at 37 °C for 6 h. The sterilized culture supernatant was analyzed, followed by data processing to create feature lists, and statistical analysis to identify discriminating features in the metabolomes of the three strains. Metabolites were identified using the exact masses, isotope patterns, and fragmentation spectra. The results showed that the metabolome of EcN differs significantly from the metabolomes of E. coli 83972 and CFT073. Based on the analysis, yersiniabactin (Ybt), its metal complexes, and its known structural derivatives escherichelin and ulbactin B were identified as discriminating features; the latter has not been described for E. coli before. Additionally, novel Ytb derivatives were found and tentatively identified by LC-MS/HRMS. All these metabolites were determined in significantly higher levels in the metabolome of EcN compared to E. coli 83972, which may explain a large part of the observed differences of the metabolomes.
Mareike Schulz; Vasiliki Gaitanoglou; Olena Mantel; Yannick Hövelmann; Florian Hübner; Ulrich Dobrindt; Hans-Ulrich Humpf. Metabolomics Study on Pathogenic and Non-pathogenic E. coli with Closely Related Genomes with a Focus on Yersiniabactin and Its Known and Novel Derivatives. Metabolites 2020, 10, 1 .
AMA StyleMareike Schulz, Vasiliki Gaitanoglou, Olena Mantel, Yannick Hövelmann, Florian Hübner, Ulrich Dobrindt, Hans-Ulrich Humpf. Metabolomics Study on Pathogenic and Non-pathogenic E. coli with Closely Related Genomes with a Focus on Yersiniabactin and Its Known and Novel Derivatives. Metabolites. 2020; 10 (6):1.
Chicago/Turabian StyleMareike Schulz; Vasiliki Gaitanoglou; Olena Mantel; Yannick Hövelmann; Florian Hübner; Ulrich Dobrindt; Hans-Ulrich Humpf. 2020. "Metabolomics Study on Pathogenic and Non-pathogenic E. coli with Closely Related Genomes with a Focus on Yersiniabactin and Its Known and Novel Derivatives." Metabolites 10, no. 6: 1.