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"pageLength" : 12, "publishedYear" : 2020, "abstractText" : "Purpose: To evaluate the efficacy of Library of Integrated Network-based Cellular Signatures (LINCS) perturbagen prediction software to identify small molecules that revert pathologic gene signature and alter disease phenotype in orbital adipose stem cells (OASCs) derived from patients with thyroid-associated orbitopathy (TAO).Methods: Differentially expressed genes identified via RNA sequencing were inputted into LINCS L1000 Characteristic Direction Signature Search Engine (L1000CDS2) to predict candidate smallmolecules to reverse pathologic gene expression. TAOOASC cell lines were treated in vitro with six identified small molecules (Torin-2, PX12, withaferin A, isoliquiritigenin, mitoxantrone, and MLN8054), and expression of key adipogenic and differentially expressed genes was measured with quantitative polymerase chain reaction after 7 days of treatment. OASCs were differentiated into adipocytes, treated for 15 days, and stained with Oil Red O (OD 490 nm) to evaluate adipogenic changes.Results: The expression of key differentially expressed genes (IRX1, HOXB2, S100B, and KCNA4) and adipogenic genes (peroxisome proliferator activated receptor-gamma, FABP4) was significantly decreased in TAO OASCs after treatment (P <.05). In treated TAO adipocytes (n= 3), all six tested small molecules yielded significant decrease (P<.05) in Oil RedOstaining. In treated non-TAOadipocytes (n= 3), only three of the drugs yielded a significant decrease in Oil Red O staining.Conclusions: Combining disease expression signatures with LINCS small molecule prediction software can identify promising preclinical drug candidates for TAO. Translational Relevance: These findings may offer insight into future potential therapeutic options for TAOand demonstrate a streamlinedmodel to predict drug candidates for other diseases.", "subjects" : [ { "otype" : "Classification", "mtid" : 12215, "link" : "/api/classification/12215", "label" : "Klinikai orvostan", "published" : true, "snippet" : true } ], "keywords" : [ { "otype" : "Keyword", "mtid" : 1030404, "link" : "/api/keyword/1030404", "label" : "Adipogenesis", "published" : true, "oldId" : 1030404, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1608859, "link" : "/api/keyword/1608859", "label" : "thyroid eye disease", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1840204, "link" : "/api/keyword/1840204", "label" : "thyroid-associated orbitopathy", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2231525, "link" : "/api/keyword/2231525", "label" : "Graves'ophthalmopathy", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2231526, "link" : "/api/keyword/2231526", "label" : "orbital adipose stem cells", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2231527, "link" : "/api/keyword/2231527", "label" : "LINCS", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2020, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : null, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2021-10-02", "oaFree" : false, "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 1, "citedCount" : 1, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10753639, "link" : "/api/sjrrating/10753639", "label" : "sjr:Q1 (2020) Scopus - Biomedical Engineering TRANSLATIONAL VISION SCIENCE AND TECHNOLOGY 2164-2591", "listPos" : 28, "rankValue" : 0.24, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 2204, "link" : "/api/classificationexternal/2204", "label" : "Scopus - Biomedical Engineering", "published" : true, "oldId" : 2204, "snippet" : true }, "ranking" : "Q1", "calculation" : "DIRECT", "published" : true, "snippet" : true } ], "ratingsForSort" : "Q1", "hasCitationDuplums" : false, "directInstitutesForSort" : "", "ownerAuthorCount" : 1, "ownerInstituteCount" : 3, "directInstituteCount" : 0, "authorCount" : 7, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/31741198", "label" : "Lee John Y. et al. 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