New Insights Into the Correlation Between Necroptotic Activation and Neutrophil Infiltration in Pulpitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40138999", "kind": "science-record", "revision": 4, "content_hash": "sha256:9f58dde647b4270d824af1becb37e84fd086ccb1c667502e99585dde4d640d4c", "created_at": "2026-11-01T20:30:20Z", "updated_at": "2026-11-01T22:56:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "New Insights Into the Correlation Between Necroptotic Activation and Neutrophil Infiltration in Pulpitis.", "doi": "10.1016/j.identj.2025.02.016", "pmid": "40138999", "authors": ["Xiaolan Guo", "Xinyan Ma", "Peng Liu", "Xiaoxin Chen", "Sitong Liu", "Longrui Dang", "Buling Wu", "Zhao Chen"], "journal": "International dental journal", "year": 2025, "abstract": "BACKGROUND: Pulpitis is a significant dental concern characterized by inflammation of the dental pulp, often causing severe pain and potential tooth loss. Immune infiltration and necroptosis, both implicated in various inflammatory conditions, have been noted in pulpitis. However, the roles of necroptosis and immune infiltration in pulpitis pathogenesis remain poorly understood.\nMETHODS: Hematoxylin and eosin (HE) staining assessed inflammatory infiltration in dental pulp tissues. Western blotting (WB) and immunohistochemistry (IHC) quantified pMLKL expression. Transcriptome datasets GSE92681 and GSE77459 from GEO identified necroptosis-related differentially expressed genes (NRDEGs) via bioinformatics analysis. Functional enrichment identified 6 hub NRDEGs based on diagnostic capability through machine learning and immune infiltration. Transwell assays evaluated neutrophil infiltration post dental pulp cells (DPCs) necroptosis. The STRING database analyzed CXCL8-activated neutrophil receptors, and Transwell and co-immunoprecipitation (Co-IP) validated ligand-receptor interactions.\nRESULTS: Increased pMLKL expression in inflamed dental pulp indicates activation of necroptosis pathways. Functional enrichment analysis revealed that NRDEGs were mainly involved in necroptosis. Both datasets showed significant inflammatory infiltration. Bioinformatics suggested a link between immune infiltration and necroptosis in DPCs, with correlation analyses showing NRDEGs were closely associated with neutrophil infiltration. Necroptotic DPCs produce CXCL8, which recruits neutrophils via the C3AR1 receptor. The CXCL8/C3AR1 axis, validated by Transwell and co-immunoprecipitation assays, is crucial for communication between necroptosis and neutrophil chemotaxis in DPCs.\nCONCLUSION: Necroptosis occurs in pulpitis and correlates with immune cell infiltration. DPCs undergoing necroptosis can recruit neutrophils via the CXCL8/C3AR1 axis, exacerbating inflammation. This study offers new insights into the pathogenesis of pulpitis and potential therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "We screened DEGs using the R package \"limma (v 3.48.3)\" and set the thresholds to P < .05 and | Log2FC | > 0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40138999", "locator": "sections[13] \"Selection of NRDEGs\" paragraph 2", "quote": "We screened DEGs using the R package \"limma (v 3.48.3)\" and set the thresholds to P < .05 and | Log2FC | > 0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40138999", "locator": "sections[32] \"ack\" paragraph 1", "quote": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Functional enrichment identified 6 hub NRDEGs based on diagnostic capability through machine learning and immune infiltration.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40138999", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Functional enrichment identified 6 hub NRDEGs based on diagnostic capability through machine learning and immune infiltration."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Functional enrichment identified 6 hub NRDEGs based on diagnostic capability through machine learning and immune infiltration.", "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:40138999"], "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:GSE77459"], "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:GSE77459"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40138999", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.identj.2025.02.016", "sha256": "sha256:d49893fc4628a0d1643e07ed0fe96d61144147e60f7b18e099aa40b8c281da73", "bytes": 36482, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.identj.2025.02.016", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11985107", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE77459", "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=GSE77459", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE77459", "version": null, "note": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2052371", "GSM2052372", "GSM2052373", "GSM2052374", "GSM2052375", "GSM2052376", "GSM2052377", "GSM2052378", "GSM2052379", "GSM2052380", "GSM2052381", "GSM2052382"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "17692", "taxon": "Homo sapiens", "title": "Gene Expression Profile of Pulpitis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE92681", "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=GSE92681", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE92681", "version": null, "note": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2434473", "GSM2434474", "GSM2434475", "GSM2434476", "GSM2434477", "GSM2434478", "GSM2434479", "GSM2434480", "GSM2434481", "GSM2434482", "GSM2434483", "GSM2434484"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "16956", "taxon": "Homo sapiens", "title": "Differential Expression of LncRNAs and mRNAs in normal and inflamed human pulp", "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:GSE77459 not downloaded", "asset:data:geo:GSE77459 licence not read", "asset:data:geo:GSE92681 not downloaded", "asset:data:geo:GSE92681 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 screened DEGs using the R package \"limma (v 3.48.3)\" and set the thresholds to P < .05 and | Log2FC | > 0.5."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "GO 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": ["GSE92681", "GSE77459"], "resolved_accessions": ["GSE92681", "GSE77459"], "statements": ["Microarray data and corresponding clinical data for patients with pulpitis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) .The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO), reference number GSE77459 and GSE92681."], "basis": "The paper names GSE92681, GSE77459 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:40138999", "data:geo:GSE77459"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE77459"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:49:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10182, "completion_tokens": 1895, "cached_tokens": 256}}, "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:40138999", "type": "paper", "label": "pmid:40138999"}, {"id": "source:pmid:40138999", "type": "manuscript", "label": "PMID 40138999 full text"}, {"id": "data:geo:GSE77459", "type": "dataset", "label": "GEO GSE77459"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40138999", "type": "paper", "label": "pmid:40138999"}, {"id": "source:pmid:40138999", "type": "manuscript", "label": "PMID 40138999 full text"}, {"id": "data:geo:GSE77459", "type": "dataset", "label": "GEO GSE77459"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40138999", "type": "extraction", "used": ["source:pmid:40138999"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE77459", "type": "accession_resolution", "used": ["data:geo:GSE77459"], "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:40138999", "parent_hash": "sha256:1984d68a2cffba83d4498247688e9fef36c902061825f6c44dfd76f90189dd9c", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE77459 licence not read", "asset:data:geo:GSE77459 not downloaded", "asset:data:geo:GSE92681 licence not read", "asset:data:geo:GSE92681 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["mmatory infiltration in dental pulp tissues. Western blotting (WB) and immunohistochemistry (IHC) quantifi"], "order_basis": "paper_text_order:547", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ntal pulp tissues. Western blotting (WB) and immunohistochemistry (IHC) quantified pMLKL expression. Transcrip", "tern blotting (WB) and immunohistochemistry (IHC) quantified pMLKL expression. Transcriptome"], "order_basis": "paper_text_order:573", "id": "assay:2"}, {"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 screened DEGs using the R package \"limma (v 3.48.3)\" and set the thresholds to P < .05 and | Log2FC | > 0.5."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}