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  1. Article ; Online: Autotaxin, PPARs, and FGF21: An Eye Opener for Progressive Liver Disease?

    Beuers, Ulrich / Oude Elferink, Ronald

    Cellular and molecular gastroenterology and hepatology

    2022  Volume 14, Issue 5, Page(s) 1168–1169

    MeSH term(s) Humans ; Peroxisome Proliferator-Activated Receptors ; Fibroblast Growth Factors ; Liver Diseases
    Chemical Substances fibroblast growth factor 21 ; Peroxisome Proliferator-Activated Receptors ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2022-09-09
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2819778-1
    ISSN 2352-345X ; 2352-345X
    ISSN (online) 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2022.08.009
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  2. Article: Long-Term Effects of Biliverdin Reductase a Deficiency in

    Bortolussi, Giulia / Shi, Xiaoxia / Ten Bloemendaal, Lysbeth / Banerjee, Bhaswati / De Waart, Dirk R / Baj, Gabriele / Chen, Weiyu / Oude Elferink, Ronald P / Beuers, Ulrich / Paulusma, Coen C / Stocker, Roland / Muro, Andrés F / Bosma, Piter J

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 12

    Abstract: Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity ... ...

    Abstract Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of
    Language English
    Publishing date 2021-12-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10122029
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  3. Article ; Online: Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice.

    Kunst, Roni F / de Waart, Dirk R / Wolters, Frank / Duijst, Suzanne / Vogels, Esther W / Bolt, Isabelle / Verheij, Joanne / Beuers, Ulrich / Oude Elferink, Ronald P J / van de Graaf, Stan F J

    JHEP reports : innovation in hepatology

    2022  Volume 4, Issue 11, Page(s) 100573

    Abstract: Background & aims: Non-absorbable inhibitors of the apical sodium-dependent bile acid transporter (ASBT; also called ileal bile acid transporter [IBAT]) are recently approved or in clinical development for multiple cholestatic liver disorders and lead ... ...

    Abstract Background & aims: Non-absorbable inhibitors of the apical sodium-dependent bile acid transporter (ASBT; also called ileal bile acid transporter [IBAT]) are recently approved or in clinical development for multiple cholestatic liver disorders and lead to a reduction in pruritus and (markers for) liver injury. Unfortunately, non-absorbable ASBT inhibitors (ASBTi) can induce diarrhoea or may be ineffective if cholestasis is extensive and largely precludes intestinal excretion of bile acids. Systemically acting ASBTi that divert bile salts towards renal excretion may alleviate these issues.
    Methods: Bile duct ligation (BDL) was performed in ASBT-deficient (ASBT knockout [KO]) mice as a model for chronic systemic ASBT inhibition in obstructive cholestasis. Co-infusion of radiolabelled taurocholate and inulin was used to quantify renal bile salt excretion after BDL. In a second (wild-type) mouse model, a combination of obeticholic acid (OCA) and intestine-restricted ASBT inhibition was used to lower the bile salt pool size before BDL.
    Results: After BDL, ASBT KO mice had reduced plasma bilirubin and alkaline phosphatase compared with wild-type mice with BDL and showed a marked reduction in liver necrotic areas at histopathological analysis, suggesting decreased BDL-induced liver damage. Furthermore, ASBT KO mice had reduced bile salt pool size, lower plasma taurine-conjugated polyhydroxylated bile salt, and increased urinary bile salt excretion. Pretreatment with OCA + ASBTi in wild-type mice reduced the pool size and greatly improved liver injury markers and liver histology.
    Conclusions: A reduced bile salt pool at the onset of cholestasis effectively lowers cholestatic liver injury in mice. Systemic ASBT inhibition may be valuable as treatment for cholestatic liver disease by lowering the pool size and increasing renal bile salt output even under conditions of minimal faecal bile salt secretion.
    Lay summary: Novel treatment approaches against cholestatic liver disease (resulting in reduced or blocked flow of bile) involve non-absorbable inhibitors of the bile acid transport protein ASBT, but these are not always effective and/or can cause unwanted side effects. In this study, we demonstrate that systemic inhibition/inactivation of ASBT protects mice against developing severe cholestatic liver injury after bile duct ligation, by reducing bile salt pool size and increasing renal bile salt excretion.
    Language English
    Publishing date 2022-08-27
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2589-5559
    ISSN (online) 2589-5559
    DOI 10.1016/j.jhepr.2022.100573
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  4. Book ; Online: Rapid changes in the North Sea require long-term roadmap

    Peck, M.A. / Bush, S.R. / Oude Elferink, A. / Rivero, S. / van Duren, L. / van Oevelen, D.

    2021  

    Abstract: For the North Sea to continue to sustain ecosystems and the social well-being of Northern Europe, action is needed by industry and policy makers alike. This is necessary to maintain biodiversity and natural productivity in the face of growing offshore ... ...

    Abstract For the North Sea to continue to sustain ecosystems and the social well-being of Northern Europe, action is needed by industry and policy makers alike. This is necessary to maintain biodiversity and natural productivity in the face of growing offshore economic activity.
    Keywords Life Science
    Language English
    Publisher SWZ Maritime
    Publishing country nl
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Conference proceedings: Serum autoantibodies against annexin A11 might weaken the biliary bicarbonate umbrella in IgG4-related cholangitis

    Herta, T. / Kersten, R. / Chang, J.-C. / Hubers, L. / Go, S. / Tolenaars, D. / Paulusma, C. C. / Nathanson, M. / Elferink, R. Oude / van de Graaf, S. F. / Beuers, U.

    Zeitschrift für Gastroenterologie

    2023  Volume 61, Issue 08

    Event/congress Viszeralmedizin 2023 77. Jahrestagung der DGVS mit Sektion Endoskopie Herbsttagung der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie mit den Arbeitsgemeinschaften der DGAV und Jahrestagung der CACP, Erst online. Dann Hamburg., 2023-09-11
    Language German
    Publishing date 2023-08-01
    Publisher Georg Thieme Verlag
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 201387-3
    ISSN 1439-7803 ; 0044-2771 ; 0172-8504
    ISSN (online) 1439-7803
    ISSN 0044-2771 ; 0172-8504
    DOI 10.1055/s-0043-1771806
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  6. Article ; Online: Soluble adenylyl cyclase regulates the cytosolic NADH/NAD

    Chang, Jung-Chin / Go, Simei / Gilglioni, Eduardo H / Duijst, Suzanne / Panneman, Daan M / Rodenburg, Richard J / Li, Hang Lam / Huang, Hsu-Li / Levin, Lonny R / Buck, Jochen / Verhoeven, Arthur J / Oude Elferink, Ronald P J

    Biochimica et biophysica acta. Bioenergetics

    2021  Volume 1862, Issue 4, Page(s) 148367

    Abstract: The evolutionarily conserved soluble adenylyl cyclase (sAC, ADCY10) mediates cAMP signaling exclusively in intracellular compartments. Because sAC activity is sensitive to local concentrations of ATP, bicarbonate, and free ... ...

    Abstract The evolutionarily conserved soluble adenylyl cyclase (sAC, ADCY10) mediates cAMP signaling exclusively in intracellular compartments. Because sAC activity is sensitive to local concentrations of ATP, bicarbonate, and free Ca
    MeSH term(s) Adenylyl Cyclases/genetics ; Adenylyl Cyclases/metabolism ; Cytosol/metabolism ; Glycolysis ; Hep G2 Cells ; Humans ; Mitochondria/genetics ; Mitochondria/metabolism ; NAD/genetics ; NAD/metabolism ; Oxidation-Reduction ; Oxidative Phosphorylation ; Oxygen Consumption
    Chemical Substances NAD (0U46U6E8UK) ; ADCY10 protein, human (EC 4.6.1.1) ; Adenylyl Cyclases (EC 4.6.1.1)
    Language English
    Publishing date 2021-01-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2650 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2650 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbabio.2020.148367
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  7. Article: Efficacy of AAV8-h

    Shi, Xiaoxia / Aronson, Sem J / Ten Bloemendaal, Lysbeth / Duijst, Suzanne / Bakker, Robert S / de Waart, Dirk R / Bortolussi, Giulia / Collaud, Fanny / Oude Elferink, Ronald P / Muro, Andrés F / Mingozzi, Federico / Ronzitti, Giuseppe / Bosma, Piter J

    Molecular therapy. Methods & clinical development

    2020  Volume 20, Page(s) 287–297

    Abstract: A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 ( ... ...

    Abstract A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 (h
    Language English
    Publishing date 2020-12-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2020.11.016
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  8. Article ; Conference proceedings: Accumulating bile salts promote liver fibrosis in cholestasis: in vivo evidence in a mouse model

    Hohenester, S / Wimmer, R / Kremer, AE / Denk, G / Florian, R / Horst, D / Oude Elferink, R / Beuers, U

    Zeitschrift für Gastroenterologie

    2019  Volume 57, Issue 01

    Event/congress 35. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Heidelberg, 2019-02-22
    Language English
    Publishing date 2019-01-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 201387-3
    ISSN 1439-7803 ; 0044-2771 ; 0172-8504
    ISSN (online) 1439-7803
    ISSN 0044-2771 ; 0172-8504
    DOI 10.1055/s-0038-1677080
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  9. Article ; Online: Role of the placenta in serum autotaxin elevation during maternal cholestasis.

    Macias, Rocio I R / Matilla, Sonia / Lozano, Elisa / Estiú, Maria C / Oude Elferink, Ronald P / Marin, Jose J G

    American journal of physiology. Gastrointestinal and liver physiology

    2018  Volume 315, Issue 3, Page(s) G399–G407

    Abstract: Intrahepatic cholestasis of pregnancy (ICP) is frequently accompanied by pruritus, whose etiology has been associated with an enhanced production of lysophosphatidic acid (LPA) by the combined action of phospholipase A1/A2 (PLA1/PLA2) and autotaxin (ATX). ...

    Abstract Intrahepatic cholestasis of pregnancy (ICP) is frequently accompanied by pruritus, whose etiology has been associated with an enhanced production of lysophosphatidic acid (LPA) by the combined action of phospholipase A1/A2 (PLA1/PLA2) and autotaxin (ATX). Here, we have investigated whether the placenta is involved in LPA release to maternal circulation during ICP. Serum levels of ATX and LPA (determined by ELISA) were elevated in women with ICP, and a correlation between both parameters was found. No relationship between serum levels of ATX or LPA and bile acids was found. Expression levels of ATX and PLA2 were determined by RT-qPCR and Western blot. Placenta ATX but not PLA2 was significantly upregulated in ICP, and a tendency to increase was found at the protein level. A correlation between serum ATX and placental ATX mRNA levels was found. In human placenta at term, ATX was clearly detected (by immunofluorescence) in Hofbauer cells, but only faintly in trophoblast cells. In pregnant rats, the expression of Atx and Pla2 in placenta was lower than in liver. When obstructive cholestasis was imposed by bile duct ligation from day 14 of gestation until term, placenta Atx and Pla2 expression was markedly enhanced, and overexpression was confirmed at the protein level for Pla2, whereas Atx protein was not detected. In conclusion, the placenta substantially participates in LPA production during gestation. This contribution is markedly higher during maternal cholestasis and hence, may be involved in ICP-associated pruritus. NEW & NOTEWORTHY Fetal placental macrophages and, to a lesser extent, trophoblast cells express high levels of autotaxin at term. An increased expression of mRNA and protein autotaxin, the key secretory enzyme responsible for the production of lysophosphatidic acid in serum, has been observed in placentas of women with cholestasis of pregnancy, which supports that the placenta can contribute to an increased production of this pruritogenic compound in women suffering from this liver disease.
    MeSH term(s) Animals ; Bile Acids and Salts/metabolism ; Cholestasis, Intrahepatic/metabolism ; Female ; Humans ; Liver/metabolism ; Lysophospholipids/blood ; Lysophospholipids/metabolism ; Phospholipases A1/metabolism ; Phospholipases A2/metabolism ; Phosphoric Diester Hydrolases/blood ; Phosphoric Diester Hydrolases/metabolism ; Placenta/metabolism ; Pregnancy ; Pregnancy Complications/metabolism ; Rats
    Chemical Substances Bile Acids and Salts ; Lysophospholipids ; Phospholipases A1 (EC 3.1.1.32) ; Phospholipases A2 (EC 3.1.1.4) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; alkylglycerophosphoethanolamine phosphodiesterase (EC 3.1.4.39) ; lysophosphatidic acid (PG6M3969SG)
    Language English
    Publishing date 2018-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00112.2018
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  10. Article ; Online: Blockade of neutrophil extracellular trap components ameliorates cholestatic liver disease in Mdr2 (Abcb4) knockout mice.

    Hintermann, Edith / Tondello, Camilla / Fuchs, Sina / Bayer, Monika / Pfeilschifter, Josef M / Taubert, Richard / Mollenhauer, Martin / Elferink, Roland P J Oude / Manns, Michael P / Christen, Urs

    Journal of autoimmunity

    2024  Volume 146, Page(s) 103229

    Abstract: Primary sclerosing cholangitis (PSC) is an (auto)immune-mediated cholestatic liver disease with a yet unclear etiology. Increasing evidence points to an involvement of neutrophils in chronic liver inflammation and cirrhosis but also liver repair. Here, ... ...

    Abstract Primary sclerosing cholangitis (PSC) is an (auto)immune-mediated cholestatic liver disease with a yet unclear etiology. Increasing evidence points to an involvement of neutrophils in chronic liver inflammation and cirrhosis but also liver repair. Here, we investigate the role of the neutrophil extracellular trap (NET) component myeloperoxidase (MPO) and the therapeutic potential of DNase I and of neutrophil elastase (NE) inhibitor GW311616A on disease outcome in the multidrug resistance 2 knockout (Mdr2
    Language English
    Publishing date 2024-04-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 639452-8
    ISSN 1095-9157 ; 0896-8411
    ISSN (online) 1095-9157
    ISSN 0896-8411
    DOI 10.1016/j.jaut.2024.103229
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