Ferroptosis-related signature and immune infiltration characterization in acute lung injury/acute respiratory distress syndrome.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37301835", "kind": "science-record", "revision": 4, "content_hash": "sha256:77290cbc52cd95ab75643644affd682f1e95e5a1a4e3b15f0485f8a59333324e", "created_at": "2026-11-01T19:02:01Z", "updated_at": "2026-11-01T22:52:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis-related signature and immune infiltration characterization in acute lung injury/acute respiratory distress syndrome.", "doi": "10.1186/s12931-023-02429-y", "pmid": "37301835", "authors": ["Aijia Ma", "Zhongxue Feng", "Yang Li", "Qin Wu", "Huaiyu Xiong", "Meiling Dong", "Jiangli Cheng", "Zhenling Wang", "Jing Yang", "Yan Kang"], "journal": "Respiratory research", "year": 2023, "abstract": "BACKGROUND: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most life-threatening diseases in the intensive care unit with high mortality and morbidity. Ferroptosis is a newly discovered immune related cell death that is associated with various lung diseases. However, the role of immune-mediated ferroptosis in ALI/ARDS has not been elucidated.\nMETHOD: We analyzed two Gene Expression Omnibus (GEO) datasets (GSE2411 and GSE109913) and extracted characteristic ferroptosis-related genes (FRGs) between the control and ALI groups through bioinformatic analysis. Then, we prospectively collected bronchoalveolar lavage fluid (BALF) from patients with ARDS and verified the expression of characteristic FRGs. Lastly, we constructed the ALI/ARDS model induced by LPS and isolated the primary neutrophils of mice. Erastin, an ferroptosis inducer, was used at the cellular level to verify the effect of neutrophils on ferroptosis in lung epithelium cells.\nRESULT: We identified three characteristic FRGs, Cp, Slc39a14 and Slc7a11, by analyzing two gene expression profiling datasets. Immune infiltration analysis showed that the three characteristic genes were significantly positively correlated with the infiltration levels of neutrophils. We collected BALF from 59 ARDS patients to verify the expression of Cp, Slc7a11 and Slc39a14 in humans. The results showed that Cp was elevated in patients with severe ARDS (p = 0.019), Slc7a11 was significantly elevated in patients with moderate ARDS (p = 0.021) relative to patients with mild ARDS. The levels of neutrophils in the peripheral blood of ARDS patients were positively correlated with the expression levels of Slc7a11 (Pearson's R2 = 0.086, p = 0.033). Three characteristic FRGs were significantly activated after the onset of ferroptosis (6 h) early in LPS induced ALI model, and that ferroptosis was alleviated after the organism compensated within 12 to 48 h. We extracted primary activated neutrophils from mice and co-cultured them with MLE-12 in transwell, Slc7a11, Cp and Slc39a14 in MLE-12 cells were significantly upregulated as the number of neutrophils increased. The results showed that neutrophil infiltration alleviated erastin-induced MDA accumulation, GSH depletion, and divalent iron accumulation, accompanied by upregulation of Slc7a11 and Gpx4, implying the existence of a compensatory effect of lipid oxidation in neutrophils after acute lung injury in the organism.\nCONCLUSION: We identified three immune-mediated ferroptosis genes, namely, Cp, Slc7a11 and Slc39a14, which possibly regulated by neutrophils during the development of ALI, and their pathways may be involved in anti-oxidative stress and anti-lipid metabolism. Thus, the present study contributes to the understanding of ALI/ARDS and provide novel targets for future immunotherapeutic.", "claims": [{"id": "claim-method", "statement": "We used the “limma” package in R (4.1.1) to detect DEGs between the control and ALI groups [16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37301835", "locator": "sections[4] \"Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "We used the “limma” package in R (4.1.1) to detect DEGs between the control and ALI groups [16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Not applicable, data was collected from public data repositories.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37301835", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "Not applicable, data was collected from public data repositories."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:37301835"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["Not applicable, data was collected from public data repositories."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37301835"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:43:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16202, "completion_tokens": 1621, "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:37301835", "type": "paper", "label": "pmid:37301835"}, {"id": "source:pmid:37301835", "type": "manuscript", "label": "PMID 37301835 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37301835", "type": "paper", "label": "pmid:37301835"}, {"id": "source:pmid:37301835", "type": "manuscript", "label": "PMID 37301835 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37301835", "type": "extraction", "used": ["source:pmid:37301835"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:37301835", "parent_hash": "sha256:6c69bfb0894fd9937e44bd936d441ec89a1c044f4c1280dfc22cf4c40c8c68c1", "fork_of": null, "generation": 3}, "gaps": ["execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"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": ["ell culture and intervention Cell culture of mouse lung epithelial cells (MLE-12) was purchased"], "order_basis": "paper_text_order:2992", "id": "assay:1"}, {"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": ["ture Collection, Manassas, USA). MLE-12 were cultured in a 37 °C humidified cell incubator with 5% CO", "e used for the co-culture. MLE-12 cells were cultured in the lower chambers with DMEM medium, and pri", "th DMEM medium, and primary neutrophils were cultured in the upper chambers with 1640 medium, for 24", "ture Collection, Manassas, USA). MLE-12 were cultured in a 37 °C humidified cell incubator with 5%"], "order_basis": "paper_text_order:3116", "id": "assay:2"}, {"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": ["R packages. Intensity and co-localisation of immunofluorescence for quantitative analysis using ImageJ (vers", "sequence list. Table S2. Antibodies used for immunofluorescence and western blot. Additional file 3: Figure"], "order_basis": "paper_text_order:4229", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s using ImageJ (version 2.0.0). For qRT-PCR, Western blot, Elisa, comparisons between groups were perf", "plementary Materials Additional file 1. Full Western blot images. Additional file 2. Methods. Table S1", ". Antibodies used for immunofluorescence and western blot. Additional file 3: Figure S1. 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