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  1. Article: Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model.

    Horánszky, Alex / Shashikadze, Bachuki / Elkhateib, Radwa / Lombardo, Salvo Danilo / Lamberto, Federica / Zana, Melinda / Menche, Jörg / Fröhlich, Thomas / Dinnyés, András

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1236243

    Abstract: Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and ... ...

    Abstract Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and differentiation, although the underlying molecular mechanisms remain under debate. The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the
    Language English
    Publishing date 2023-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1236243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model

    Lamberto, Federica / Shashikadze, Bachuki / Elkhateib, Radwa / Lombardo, Salvo Danilo / Horánszky, Alex / Balogh, Andrea / Kistamás, Kornél / Zana, Melinda / Menche, Jörg / Fröhlich, Thomas / Dinnyés, András

    Environmental Pollution. 2023 Aug. 09, p.122359-

    2023  , Page(s) 122359–

    Abstract: Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical ... ...

    Abstract Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical widely used in plastics manufacturing, has been associated with heart developmental defects, even in low concentrations. This study aims to investigate the effects of environmentally relevant doses of BPA on developing cardiomyocytes using a human induced pluripotent stem cell (hiPSC)-derived model. Firstly, a 2D in vitro differentiation system to obtain cardiomyocytes from hiPSCs (hiPSC-CMs) have been established and characterised to provide a suitable model for the early stages of cardiac development. Then, the effects of a repeated BPA exposure, starting from the undifferentiated stage throughout the differentiation process, were evaluated. The chemical significantly decreased the beat rate of hiPSC-CMs, extending the contraction and relaxation time in a dose-dependent manner. Quantitative proteomics analysis revealed a high abundance of basement membrane (BM) components (e.g., COL4A1, COL4A2, LAMC1, NID2) and a significant increase in TNNC1 and SERBP1 proteins in hiPSC-CMs treated with BPA. Network analysis of proteomics data supported altered extracellular matrix remodelling and provided a disease-gene association with well-known pathological conditions of the heart. Furthermore, upon hypoxia-reoxygenation challenge, hiPSC-CMs treated with BPA showed higher rate of apoptotic events. Taken together, our results revealed that a long-term treatment, even with low doses of BPA, interferes with hiPSC-CMs functionality and alters the surrounding cellular environment, providing new insights about diseases that might arise upon the toxin exposure. Our study contributes to the current understanding of BPA effects on developing human foetal cardiomyocytes, in correlation with human clinical observations and animal studies, and it provides a suitable model for New Approach Methodologies (NAMs) for environmental chemical hazard and risk assessment.
    Keywords apoptosis ; basement membrane ; bisphenol A ; cardiomyocytes ; chemical hazards ; dose response ; embryogenesis ; extracellular matrix ; fetus ; humans ; models ; pollution ; proteomics ; risk assessment ; stem cells ; toxins ; Developmental origins of health and disease ; Human induced pluripotent stem cell ; Cardiomyocyte differentiation ; Hypoxia-reoxygenation
    Language English
    Dates of publication 2023-0809
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 280652-6
    ISSN 1873-6424 ; 0013-9327 ; 0269-7491
    ISSN (online) 1873-6424
    ISSN 0013-9327 ; 0269-7491
    DOI 10.1016/j.envpol.2023.122359
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4136: Show issues

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  3. Article ; Online: Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model.

    Lamberto, Federica / Shashikadze, Bachuki / Elkhateib, Radwa / Lombardo, Salvo Danilo / Horánszky, Alex / Balogh, Andrea / Kistamás, Kornél / Zana, Melinda / Menche, Jörg / Fröhlich, Thomas / Dinnyés, András

    Environmental pollution (Barking, Essex : 1987)

    2023  Volume 335, Page(s) 122359

    Abstract: Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical ... ...

    Abstract Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical widely used in plastics manufacturing, has been associated with heart developmental defects, even in low concentrations. This study aims to investigate the effects of environmentally relevant doses of BPA on developing cardiomyocytes using a human induced pluripotent stem cell (hiPSC)-derived model. Firstly, a 2D in vitro differentiation system to obtain cardiomyocytes from hiPSCs (hiPSC-CMs) have been established and characterised to provide a suitable model for the early stages of cardiac development. Then, the effects of a repeated BPA exposure, starting from the undifferentiated stage throughout the differentiation process, were evaluated. The chemical significantly decreased the beat rate of hiPSC-CMs, extending the contraction and relaxation time in a dose-dependent manner. Quantitative proteomics analysis revealed a high abundance of basement membrane (BM) components (e.g., COL4A1, COL4A2, LAMC1, NID2) and a significant increase in TNNC1 and SERBP1 proteins in hiPSC-CMs treated with BPA. Network analysis of proteomics data supported altered extracellular matrix remodelling and provided a disease-gene association with well-known pathological conditions of the heart. Furthermore, upon hypoxia-reoxygenation challenge, hiPSC-CMs treated with BPA showed higher rate of apoptotic events. Taken together, our results revealed that a long-term treatment, even with low doses of BPA, interferes with hiPSC-CMs functionality and alters the surrounding cellular environment, providing new insights about diseases that might arise upon the toxin exposure. Our study contributes to the current understanding of BPA effects on developing human foetal cardiomyocytes, in correlation with human clinical observations and animal studies, and it provides a suitable model for New Approach Methodologies (NAMs) for environmental chemical hazard and risk assessment.
    MeSH term(s) Animals ; Humans ; Myocytes, Cardiac ; Induced Pluripotent Stem Cells/metabolism ; Cell Differentiation
    Chemical Substances bisphenol A (MLT3645I99)
    Language English
    Publishing date 2023-08-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 280652-6
    ISSN 1873-6424 ; 0013-9327 ; 0269-7491
    ISSN (online) 1873-6424
    ISSN 0013-9327 ; 0269-7491
    DOI 10.1016/j.envpol.2023.122359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2599: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Maternal hyperglycemia induces alterations in hepatic amino acid, glucose and lipid metabolism of neonatal offspring: Multi-omics insights from a diabetic pig model.

    Shashikadze, Bachuki / Valla, Libera / Lombardo, Salvo Danilo / Prehn, Cornelia / Haid, Mark / Riols, Fabien / Stöckl, Jan Bernd / Elkhateib, Radwa / Renner, Simone / Rathkolb, Birgit / Menche, Jörg / Hrabĕ de Angelis, Martin / Wolf, Eckhard / Kemter, Elisabeth / Fröhlich, Thomas

    Molecular metabolism

    2023  Volume 75, Page(s) 101768

    Abstract: Objective: To gain mechanistic insights into adverse effects of maternal hyperglycemia on the liver of neonates, we performed a multi-omics analysis of liver tissue from piglets developed in genetically diabetic (mutant INS gene induced diabetes of ... ...

    Abstract Objective: To gain mechanistic insights into adverse effects of maternal hyperglycemia on the liver of neonates, we performed a multi-omics analysis of liver tissue from piglets developed in genetically diabetic (mutant INS gene induced diabetes of youth; MIDY) or wild-type (WT) pigs.
    Methods: Proteome, metabolome and lipidome profiles of liver and clinical parameters of serum samples from 3-day-old WT piglets (n = 9) born to MIDY mothers (PHG) were compared with those of WT piglets (n = 10) born to normoglycemic mothers (PNG). Furthermore, protein-protein interaction network analysis was used to reveal highly interacting proteins that participate in the same molecular mechanisms and to relate these mechanisms with human pathology.
    Results: Hepatocytes of PHG displayed pronounced lipid droplet accumulation, although the abundances of central lipogenic enzymes such as fatty acid-synthase (FASN) were decreased. Additionally, circulating triglyceride (TG) levels were reduced as a trend. Serum levels of non-esterified free fatty acids (NEFA) were elevated in PHG, potentially stimulating hepatic gluconeogenesis. This is supported by elevated hepatic phosphoenolpyruvate carboxykinase (PCK1) and circulating alanine transaminase (ALT) levels. Even though targeted metabolomics showed strongly elevated phosphatidylcholine (PC) levels, the abundances of multiple key enzymes involved in major PC synthesis pathways - most prominently those from the Kennedy pathway - were paradoxically reduced in PHG liver. Conversely, enzymes involved in PC excretion and breakdown such as PC-specific translocase ATP-binding cassette 4 (ABCB4) and phospholipase A2 were increased in abundance.
    Conclusions: Our study indicates that maternal hyperglycemia without confounding obesity induces profound molecular changes in the liver of neonatal offspring. In particular, we found evidence for stimulated gluconeogenesis and hepatic lipid accumulation independent of de novo lipogenesis. Reduced levels of PC biosynthesis enzymes and increased levels of proteins involved in PC translocation or breakdown may represent counter-regulatory mechanisms to maternally elevated PC levels. Our comprehensive multi-omics dataset provides a valuable resource for future meta-analysis studies focusing on liver metabolism in newborns from diabetic mothers.
    MeSH term(s) Infant, Newborn ; Pregnancy ; Female ; Animals ; Humans ; Swine ; Adolescent ; Glucose/metabolism ; Lipid Metabolism ; Amino Acids/metabolism ; Multiomics ; Liver/metabolism ; Diabetes, Gestational ; Hyperglycemia/metabolism
    Chemical Substances Glucose (IY9XDZ35W2) ; Amino Acids
    Language English
    Publishing date 2023-07-04
    Publishing country Germany
    Document type Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2023.101768
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: FKBP51 in the Oval Bed Nucleus of the Stria Terminalis Regulates Anxiety-Like Behavior.

    Engelhardt, Clara / Tang, Fiona / Elkhateib, Radwa / Bordes, Joeri / Brix, Lea Maria / van Doeselaar, Lotte / Häusl, Alexander S / Pöhlmann, Max L / Schraut, Karla / Yang, Huanqing / Chen, Alon / Deussing, Jan M / Schmidt, Mathias V

    eNeuro

    2021  Volume 8, Issue 6

    Abstract: The cochaperone FKBP51, encoded by ... ...

    Abstract The cochaperone FKBP51, encoded by the
    MeSH term(s) Animals ; Anxiety ; Hypothalamo-Hypophyseal System ; Mice ; Neuropeptides ; Pituitary-Adrenal System ; Septal Nuclei ; Tacrolimus Binding Proteins
    Chemical Substances Neuropeptides ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
    Language English
    Publishing date 2021-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0425-21.2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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