The implementation of drug reposition for alcoholic hepatitis based on a sub-pathway integration strategy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32309355", "kind": "science-record", "revision": 8, "content_hash": "sha256:84e798358d94184669e2b266d4fe4aafd299c9566da927309190e6fe9be892d7", "created_at": "2026-11-01T15:40:59Z", "updated_at": "2026-11-01T22:01:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The implementation of drug reposition for alcoholic hepatitis based on a sub-pathway integration strategy.", "doi": "10.21037/atm.2020.01.36", "pmid": "32309355", "authors": ["Wei Qi", "Bing Wang", "Ming Yang", "Lin Zhu", "Sen Hu", "Hui Sun"], "journal": "Annals of translational medicine", "year": 2020, "abstract": "BACKGROUND: Alcoholic hepatitis (AH) is one of the most severe forms of liver disease. The therapies which are currently available are not entirely effective, and thus novel therapies are urgently needed. However, the development of these novel therapies is limited due to incomplete information about the molecular mechanisms involved in AH.\nMETHODS: The microarray data (GSE28619) was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between the AH and the control samples were identified using the significant analysis of microarrays (SAM) method. Metabolic sub-pathways were identified using the SubpathwayMiner R package. Cell Counting Kit-8 (CCK-8) was used to evaluate the cell viability of AML-12 cells treated with different concentrations of ethanol or riboflavin. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were employed to show the hepatocyte function.\nRESULTS: A total of 1,041 genes were determined to be expressed differentially. We then identified 11 metabolic sub-pathways that could be involved in the development of AH. This was followed by a final integrated analysis of the sub-pathways involved in AH as well as the sub-pathways involved in the drug-affected cases. The final integration results led to the identification of 64 small molecular drugs. A potential novel drug (riboflavin) involved in the fatty acid metabolism pathway was identified for further investigation. Riboflavin at the 60 nM for 24 h could reverse ethanol-induced AML-12 cell injury and could markedly decrease ALT and AST activity. The decrease in the activities of these two enzymes was observed in a dose-dependent manner when it was compared to ethanol alone, which suggests that riboflavin has a protective effect against liver cell injury caused by alcoholism.\nCONCLUSIONS: To summarize, the candidate agents which are identified in the present study might give practitioners insight into the development of novel therapeutic approaches for AH.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes (DEGs) between the AH and the control samples were identified using the significant analysis of microarrays (SAM) method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32309355", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The differentially expressed genes (DEGs) between the AH and the control samples were identified using the significant analysis of microarrays (SAM) method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Microarray data for GSE28619 were obtained from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) provided by the National Center of Biotechnology Information (NCBI). In this profile, hepatic gene expression was assessed in patients with AH (n=15) and controls with normal livers (n=7) using the Affymetrix Human Genome U133 Plus 2.0 Array platform (6).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32309355", "locator": "sections[3] \"Identification of gene expression using microarray data\" paragraph 2", "quote": "Microarray data for GSE28619 were obtained from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) provided by the National Center of Biotechnology Information (NCBI). In this profile, hepatic gene expression was assessed in patients with AH (n=15) and controls with normal livers (n=7) using the Affymetrix Human Genome U133 Plus 2.0 Array platform (6)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32309355"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE28619"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE28619"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32309355", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm.2020.01.36", "sha256": "sha256:c502a3c2dd00b00159f5e7b491956700cdeffc1c80ea83df9bbcc59d6770d17a", "bytes": 22034, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm.2020.01.36", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7154418", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28619", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28619", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28619", "version": null, "note": "Microarray data for GSE28619 were obtained from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) provided by the National Center of Biotechnology Information (NCBI). In this profile, hepatic gene expression was assessed in patients with AH (n=15) and controls with normal livers (n=7) using the Affymetrix Human Genome U133 Plus 2.0 Array platform (6).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Microarray data for GSE28619 were obtained from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) provided by the National Center of Biotechnology Information (NCBI). In this profile, hepatic gene expression was assessed in patients with AH (n=15) and controls with normal livers (n=7) using the Affymetrix Human Genome U133 Plus 2.0 Array platform (6).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM709348", "GSM709349", "GSM709350", "GSM709351", "GSM709352", "GSM709353", "GSM709354", "GSM709355", "GSM709356", "GSM709357", "GSM709358", "GSM709359", "GSM709360", "GSM709361", "GSM709362", "GSM709363", "GSM709364", "GSM709365", "GSM709366", "GSM709367", "GSM709368", "GSM709369"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Transcriptome Analysis Identifies Fn14, a TNF Superfamily Receptor Member, as a Therapeutic Target in Alcoholic Hepatitis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32309355:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e3966f26eda33faaea3df524d324a105a55667b77232ff819187bbbae9269af9", "bytes": 976, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t1", "version": null, "note": "Enriched sub-pathways and their corresponding entire pathways", "structure": {"pmcid": "PMC7154418", "section_index": 12, "section_title": "Exploration of the AH mechanism based on sub-pathway enrichment analysis", "row_count": 12, "column_count": 4}, "table": {"label": "Table 1", "caption": "Enriched sub-pathways and their corresponding entire pathways", "rows": [["Sub-pathway ID", "Pathway name", "P value", "Gene number"], ["Path:00071_2", "Fatty acid metabolism", "2.97E-06", "20"], ["Path:00120_3", "Bile acid biosynthesis", "0.004102891", "8"], ["Path:00120_4", "Bile acid biosynthesis", 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"read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t2", "version": null, "note": "Potential drugs and their information", "structure": {"pmcid": "PMC7154418", "section_index": 13, "section_title": "AH drug repositions", "row_count": 65, "column_count": 3}, "table": {"label": "Table 2", "caption": "Potential drugs and their information", "rows": [["Drug ID", "Drug name", "Number of overlaps"], ["", "Raubasine", "5"], ["", "Pipenzolate bromide", "5"], ["", "Azaperone", "5"], ["DB00338", "Omeprazole", "5"], ["", "Tiapride", "5"], ["", "Etanidazole", "5"], ["DB01438", "Phenazopyridine", "5"], ["DB00692", "Phentolamine", "5"], ["DB00759", "Tetracycline", "5"], ["DB00714", "Apomorphine", "5"], ["DB01392", "Yohimbine", "5"], ["", "Acemetacin", "5"], ["DB00553", "Methoxsalen", "5"], ["DB00448", "Lansoprazole", "5"], ["DB00734", "Risperidone", "5"], ["DB02187", "Equilin", "5"], ["DB00904", "Ondansetron", "5"], ["DB00140", "Riboflavin", "5"], ["DB00450", 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