{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:30:34Z","timestamp":1762065034821,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor\u2019s liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora\u2019s d., Andersen\u2019s d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility.<\/jats:p>","DOI":"10.3390\/ijms23179996","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:19:01Z","timestamp":1662077941000},"page":"9996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation"],"prefix":"10.3390","volume":"23","author":[{"given":"Francesco","family":"Callea","sequence":"first","affiliation":[{"name":"Department of Pathology, Catholic University Bugando Medical Centre, Mwanza P.O. Box 1464, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-2383","authenticated-orcid":false,"given":"Paola","family":"Francalanci","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-9286","authenticated-orcid":false,"given":"Chiara","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Children Hospital Meyer, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Diomedi","family":"Camassei","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7450-8398","authenticated-orcid":false,"given":"Rita","family":"Devito","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Facchetti","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Brescia Spedali Civili, 25121 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Alaggio","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-849X","authenticated-orcid":false,"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Area di Ricerca Genetica e Malattie Rare, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s00428-019-02633-6","article-title":"Update on polyglucosan storage diseases","volume":"475","author":"Cenacchi","year":"2019","journal-title":"Virchows Arch"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e12761","DOI":"10.1111\/nan.12761","article-title":"Proteomic characterisation of polyglucosan bodies in skeletal muscle in RBCK1 deficiency","volume":"48","author":"Thomsen","year":"2022","journal-title":"Neuropathol. 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