The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39296166", "kind": "science-record", "revision": 4, "content_hash": "sha256:3a7a8486a368ac76dc05d27d068d1757dd9e5a82297faf43389e78e85cb59c33", "created_at": "2026-11-01T20:29:28Z", "updated_at": "2026-11-01T22:55:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway.", "doi": "10.1016/j.heliyon.2024.e36111", "pmid": "39296166", "authors": ["Min Fu", "Li Zhengran", "Li Yingli", "Wu Tong", "Cai Liyang", "Guo Xi", "Yang Xiongyi", "Cao Mingzhe", "Yi Guoguo"], "journal": "Heliyon", "year": 2024, "abstract": "Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.", "claims": [{"id": "claim-method", "statement": "We used the \"limma\" package [30] to examine DEGs in DR and control samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39296166", "locator": "sections[6] \"Data processing and identification of DEGs\" paragraph 2", "quote": "We used the \"limma\" package [30] to examine DEGs in DR and control samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39296166", "locator": "sections[44] \"Data availability statement\" paragraph 2", "quote": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39296166", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.", "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:39296166"], "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:GSE209872"], "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:GSE209872"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39296166", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e36111", "sha256": "sha256:c50934b24dafe3f715a5dd16f2c191f4d3323a6459fdb96c604f1c79844ecad8", "bytes": 50283, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e36111", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11409038", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE209872", "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=GSE209872", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE209872", "version": null, "note": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM6403183", "GSM6403184", "GSM6403185", "GSM6403186", "GSM6403187"], "sample_count": 5, "group_sizes": null, "group_sizes_basis": null, "platform": "25947", "taxon": "Rattus norvegicus", "title": "Single-cell RNA Sequencing of rats in early diabetic retinopathy", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE60436", "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=GSE60436", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE60436", "version": null, "note": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1479904", "GSM1479905", "GSM1479906", "GSM1479907", "GSM1479908", "GSM1479909", "GSM1479910", "GSM1479911", "GSM1479912"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "6884", "taxon": "Homo sapiens", "title": "Gene Expression Profile of Fibrovascular Membrane Associated with Proliferative Diabetic Retinopathy", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE209872 not downloaded", "asset:data:geo:GSE209872 licence not read", "asset:data:geo:GSE60436 not downloaded", "asset:data:geo:GSE60436 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We used the \"limma\" package [30] to examine DEGs in DR and control samples."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE60436", "GSE209872"], "resolved_accessions": ["GSE60436", "GSE209872"], "statements": ["The GEO dataset can be found in GSE60436 in https://www.ncbi.nlm.nih.gov/geo/ Single-cell assay data can also be found in GSE209872 in https://www.ncbi.nlm.nih.gov/geo/ The other original data can be asked from the authors if needed. All analysis was conducted by R 4.2.3."], "basis": "The paper names GSE60436, GSE209872 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:39296166", "data:geo:GSE209872"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE209872"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:32:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14391, "completion_tokens": 1304, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:39296166", "type": "paper", "label": "pmid:39296166"}, {"id": "source:pmid:39296166", "type": "manuscript", "label": "PMID 39296166 full text"}, {"id": "data:geo:GSE209872", "type": "dataset", "label": "GEO GSE209872"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39296166", "type": "paper", "label": "pmid:39296166"}, {"id": "source:pmid:39296166", "type": "manuscript", "label": "PMID 39296166 full text"}, {"id": "data:geo:GSE209872", "type": "dataset", "label": "GEO GSE209872"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39296166", "type": "extraction", "used": ["source:pmid:39296166"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE209872", "type": "accession_resolution", "used": ["data:geo:GSE209872"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:39296166", "parent_hash": "sha256:3599bfe81a3d15d3361b0b2a174e5767f09b11b4dad81e8ada6e1b6318697f5a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE209872 licence not read", "asset:data:geo:GSE209872 not downloaded", "asset:data:geo:GSE60436 licence not read", "asset:data:geo:GSE60436 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ated to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Om"], "order_basis": "paper_text_order:309", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADI", "the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene ex", "GE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts"], "order_basis": "paper_text_order:769", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ents. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADI"], "order_basis": "paper_text_order:781", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["expression as the disease progressed in our mouse models. At the protein level, ELISA results"], "order_basis": "paper_text_order:894", "id": "assay:4"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 cont", "idenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a centra"], "order_basis": "paper_text_order:929", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We used the \"limma\" package [30] to examine DEGs in DR and control samples."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}