{"id":"3648693d-5a8d-5f7b-b149-ef2d24ac2d4e","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:p65-null","predicate":"no_detected_change_in_recorded_experiment","statement":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"5575ee37-8a39-554f-b77c-26742e9a8c7e","mechanism_event_label":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","subject":{"id":"415608c3-d57b-5b17-aa69-c19e547330b9","slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"},"object":{"id":"23e0d759-68cd-582e-8e28-e667c8ae2c94","slug":"human-hcaec-p65-phosphorylation","display_name":"NF-kappa-B p65 phosphorylation in human coronary-artery endothelial cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5575ee37-8a39-554f-b77c-26742e9a8c7e","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:p65-null-event","event_type":"experimental_observation","label":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","description":"**Low-concentration mixtures can change VCAM-1 without a universal IL-6 effect.** Warner's 2017 study reconstructed the tracer cohort's 1-, 6- and 24-hour serum signatures. Mixtures reduced TNF-stimulated VCAM-1; some effects remained at total concentrations of 0.19–0.44 µM. IL-6 secretion decreased in HUVECs at selected higher mixture concentrations, but not detectably in HCAECs. TNF stimulation also differed between the cell types. Figure 3 preserves this important cell-specific null. Phosphorylated NF-κB p65 did not significantly change in the tested HCAEC experiment. These are mixture findings, not proof that PCA alone suppresses NF-κB at dietary exposure. [Warner et al., 2017, Figures 2–5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"415608c3-d57b-5b17-aa69-c19e547330b9","slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"},"role":"tested factor","stoichiometry":null,"state_label":"C3G-derived metabolite signatures plus TNF","sequence_order":0,"notes":""},{"entity":{"id":"23e0d759-68cd-582e-8e28-e667c8ae2c94","slug":"human-hcaec-p65-phosphorylation","display_name":"NF-kappa-B p65 phosphorylation in human coronary-artery endothelial cells","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"no_detected_change","sequence_order":1,"notes":""},{"entity":{"id":"fed11f0e-a497-5f77-8d68-7756e1c4b112","slug":"human-rela","display_name":"Human NF-kappa-B subunit RelA / RELA","entity_type_key":"protein"},"role":"p65 protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"600d5b09-e092-5146-af1e-2510cf17bac6","slug":"tnf","display_name":"Tumor necrosis factor","entity_type_key":"cytokine"},"role":"joint challenge","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"added","comparator":"TNF plus vehicle","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"}},{"dimension":"experimental_condition","value_text":"present","comparator":"TNF plus vehicle","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"tnf","display_name":"Tumor necrosis factor","entity_type_key":"cytokine"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"C3G-derived metabolite signatures plus TNF\", \"comparator\": \"TNF plus vehicle\", \"endpoint\": \"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.\", \"effect_direction\": \"no_detected_change\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"c3g-human-serum-metabolite-signatures\", \"state\": \"added\"}, {\"entity_slug\": \"tnf\", \"state\": \"present\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"HCAEC, Figure 5; highest tested mixture concentrations, brief TNF-stimulated phosphorylation assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Phosphorylation endpoint at specified sampling, not proof of absent signaling at every time or in all cell types.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells. | 2017 | DOI 10.1002/mnfr.201700053 | PMID 28457017 | https://pubmed.ncbi.nlm.nih.gov/28457017/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/ | https://doi.org/10.1002/mnfr.201700053","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 58-58; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5397eec4-e7c4-5287-85b3-7a14f04c0afc","evidence_kind":"source_excerpt","locator":"Lines 58-58","start_line":58,"end_line":58,"excerpt":"**Low-concentration mixtures can change VCAM-1 without a universal IL-6 effect.** Warner's 2017 study reconstructed the tracer cohort's 1-, 6- and 24-hour serum signatures. Mixtures reduced TNF-stimulated VCAM-1; some effects remained at total concentrations of 0.19–0.44 µM. IL-6 secretion decreased in HUVECs at selected higher mixture concentrations, but not detectably in HCAECs. TNF stimulation also differed between the cell types. Figure 3 preserves this important cell-specific null. Phosphorylated NF-κB p65 did not significantly change in the tested HCAEC experiment. These are mixture findings, not proof that PCA alone suppresses NF-κB at dietary exposure. [Warner et al., 2017, Figures 2–5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/).","model_system":"HCAEC, Figure 5; highest tested mixture concentrations, brief TNF-stimulated phosphorylation assay.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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Not publisher full text or independent replication.","file_path":"","sha256":"7cff1a47fbd9c625412b84162b1c823004b4162b7c009f9a11d5807fb8e04ef9","revision_id":"1bd4fa42-bfeb-5148-8250-fc363d8c1de0","review_status":"unverified_draft","notes":""}}],"relations":[{"id":"d9fb5969-d1b7-5b44-972f-d5a027445a5e","relation_type":"limits_scope_of","notes":"VCAM-1 reduction did not demonstrate phospho-p65 suppression in the measured assay.","source_claim_id":"3648693d-5a8d-5f7b-b149-ef2d24ac2d4e","source_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:p65-null","source_statement":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","target_claim_id":"460fe03a-05b3-5727-ae08-9b5af7634021","target_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:hcaec-vcam","target_statement":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions."}],"conflicts":[],"corrections":[],"research":null}