Tabersonine inhibits inflammation and apoptosis through the JAK1/STAT3 signaling pathway to alleviate LPS-induced acute lung injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40998926", "kind": "science-record", "revision": 4, "content_hash": "sha256:3def1a624331141e166efe9b91dce3546ccb51e8a2be8122d9f940d6ae31791c", "created_at": "2026-11-01T20:31:04Z", "updated_at": "2026-11-01T22:57:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tabersonine inhibits inflammation and apoptosis through the JAK1/STAT3 signaling pathway to alleviate LPS-induced acute lung injury.", "doi": "10.1038/s41598-025-17885-3", "pmid": "40998926", "authors": ["Mingxia Ji", "Mengyan Chen", "Ning Zhang"], "journal": "Scientific reports", "year": 2025, "abstract": "Tabersonine (Tab) holds potential therapeutic value for acute lung injury (ALI), but its mechanism remains unraveled. In order to delve into the mechanism of Tab in ALI treatment, our research group initially conducted a network pharmacology prediction. The GSE225664 single-cell transcriptome data set concerning ALI was downloaded from the GEO database. Differential expression analysis combined with weighted gene co-expression network analysis were carried out for identifying ALI-related genes. The drug-related database was employed for the prediction of Tab targets. 28 ALI-Tab targets were predicted through network pharmacology. Core target identification, KEGG pathway enrichment analysis, and molecular docking revealed that Janus kinase 1 (JAK1) is the potential target and the JAK-signal transducer and activator of transcription (STAT) signaling pathway is the potential target pathway for Tab in the treatment of ALI. An ALI mouse model, along with a RAW264.7 cell model, was established through lipopolysaccharide (LPS) stimulation, with Tab administered as an intervention. Cells were pretreated with the JAK1 inhibitor. Lung tissue injury and inflammation was evaluated based on six parameters: (1) lung tissue histopathological features, (2) lung wet/dry ratio, (3) inflammatory cell count in bronchoalveolar lavage fluid, (4) total protein concentration, (5) lactate dehydrogenase, and (6) proinflammatory factors. Cell activity was assessed through cell counting kit-8 assay. TdT-mediated dUTP nick-end labeling staining, Western blot, and flow cytometry were adopted to detect apoptosis. Tab pretreatment was proven to be effective in alleviating inflammation in mice with LPS-induced ALI and LPS-stimulated RAW264.7 cells, and suppressing the JAK1/STAT3 signaling pathway activation. Co-culturing LPS-stimulated RAW264.7 cells with A549 cells led to significantly reduced A549 cell apoptosis. Further research demonstrated that the overexpression of JAK1 significantly inhibit the effects of Tab. The foregoing results prove that LPS-induced ALI is attenuated by Tab treatment, with the underlying mechanism believed to involve the JAK1/STAT3 pathway-mediated inflammation and apoptosis.", "claims": [{"id": "claim-method", "statement": "A one-way ANOVA was applied for carrying out comparison between groups, and Sidak’s multiple comparisons test was employed for conducting post-hoc analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40998926", "locator": "sections[18] \"Statistical analysis\" paragraph 2", "quote": "A one-way ANOVA was applied for carrying out comparison between groups, and Sidak’s multiple comparisons test was employed for conducting post-hoc analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The corresponding author is responsible for resolving any queries related to this article, and data supporting the findings of this study will be made available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40998926", "locator": "sections[34] \"Data availability\" paragraph 2", "quote": "The corresponding author is responsible for resolving any queries related to this article, and data supporting the findings of this study will be made available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The foregoing results prove that LPS-induced ALI is attenuated by Tab treatment, with the underlying mechanism believed to involve the JAK1/STAT3 pathway-mediated inflammation and apoptosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40998926", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The foregoing results prove that LPS-induced ALI is attenuated by Tab treatment, with the underlying mechanism believed to involve the JAK1/STAT3 pathway-mediated inflammation and apoptosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The foregoing results prove that LPS-induced ALI is attenuated by Tab treatment, with the underlying mechanism believed to involve the JAK1/STAT3 pathway-mediated inflammation and apoptosis.", "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:40998926"], "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:GSE225664"], "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:GSE225664"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40998926", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-17885-3", "sha256": "sha256:e8baed67c0291fe40dc98e07b081ad738c3d3863ebf3b70552c69322f5f1a895", "bytes": 40736, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-17885-3", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12464169", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE225664", "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=GSE225664", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE225664", "version": null, "note": "The corresponding author is responsible for resolving any queries related to this article, and data supporting the findings of this study will be made available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The corresponding author is responsible for resolving any queries related to this article, and data supporting the findings of this study will be made available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM7053950", "GSM7053951", "GSM7053952", "GSM7053953", "GSM7053954", "GSM7053955"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "19057", "taxon": "Mus musculus", "title": "Coordinated chemokine expression defines macrophage subsets across tissues [scRNA-seq: mLu]", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE225664 not downloaded", "asset:data:geo:GSE225664 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A one-way ANOVA was applied for carrying out comparison between groups, and Sidak’s multiple comparisons test was employed for conducting post-hoc analysis."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Principal component analysis"}}, {"id": "method-3", "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": "protein-protein interaction"}}, {"id": "method-4", "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["GSE225664"], "resolved_accessions": ["GSE225664"], "statements": ["The corresponding author is responsible for resolving any queries related to this article, and data supporting the findings of this study will be made available from the corresponding author upon reasonable request."], "basis": "The paper names GSE225664 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:40998926", "data:geo:GSE225664"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE225664"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:01:53Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12372, "completion_tokens": 802, "cached_tokens": 264}}, "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:40998926", "type": "paper", "label": "pmid:40998926"}, {"id": "source:pmid:40998926", "type": "manuscript", "label": "PMID 40998926 full text"}, {"id": "data:geo:GSE225664", "type": "dataset", "label": "GEO GSE225664"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40998926", "type": "paper", "label": "pmid:40998926"}, {"id": "source:pmid:40998926", "type": "manuscript", "label": "PMID 40998926 full text"}, {"id": "data:geo:GSE225664", "type": "dataset", "label": "GEO GSE225664"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40998926", "type": "extraction", "used": ["source:pmid:40998926"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE225664", "type": "accession_resolution", "used": ["data:geo:GSE225664"], "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:40998926", "parent_hash": "sha256:06b22d1706b03800afb7779ed8b20352fa68b5ea89725eacce1a3c467beebc14", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE225664 licence not read", "asset:data:geo:GSE225664 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Tabersonine inhibits inflammation and apoptosis through the JAK1/STAT3 signaling pathway to", "t, and flow cytometry were adopted to detect apoptosis. Tab pretreatment was proven to be effective", "cells led to significantly reduced A549 cell apoptosis. Further research demonstrated that the over", "JAK1/STAT3 pathway-mediated inflammation and apoptosis."], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["hway for Tab in the treatment of ALI. An ALI mouse model, along with a RAW264.7 cell model, was estab", "to be effective in alleviating inflammation in mice with LPS-induced ALI and LPS-stimulated RAW2", "hway for Tab in the treatment of ALI. An ALI mouse model, along with a RAW264.7 cell model, was", "ion and grouping Eight-week-old male C57BL/6 mice were procured from an accredited supplier and kep"], "order_basis": "paper_text_order:1028", "id": "assay:2"}, {"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": ["dT-mediated dUTP nick-end labeling staining, Western blot, and flow cytometry were adopted to detect a"], "order_basis": "paper_text_order:1631", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ick-end labeling staining, Western blot, and flow cytometry were adopted to detect apoptosis. Tab pretre"], "order_basis": "paper_text_order:1649", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["culturing LPS-stimulated RAW264.7 cells with A549 cells led to significantly reduced A549 cell", "with A549 cells led to significantly reduced A549 cell apoptosis. Further research demonstrate", "AW264.7 cells (CL-0190, Procell, China) were cultured in Dulbecco’s Modified Eagle Medium (C11330500B", "64.7 cell supernatant was taken to stimulate A549 cells (CL-0016, Procell, China) for 24 h. Af"], "order_basis": "paper_text_order:1943", "id": "assay:5"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["K1 were constructed using Lipofectamine 3000 transfection reagent (L3000150, Thermo Fisher Scientific,"], "order_basis": "paper_text_order:6906", "id": "assay:6"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["A one-way ANOVA was applied for carrying out comparison between groups, and Sidak’s multiple comparisons test was employed for conducting post-hoc analysis."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}