{"id":"14e069e5-84ac-5e98-b619-0416bd7043a4","stable_key":"18100170-a014-51c3-adeb-9dab4162b8cc:aged-il6-site","predicate":"context_dependent_observation","statement":"Mutation of an NF-kappa-B site in the mouse Il6 reporter removed the inhibitory reporter effect of thymulin treatment.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6b4a9b11-284c-5285-b818-c3efc2493b6a","mechanism_event_label":"Mutation of an NF-kappa-B site in the mouse Il6 reporter removed the inhibitory reporter effect of thymulin treatment.","subject":{"id":"23819462-9bdf-5856-beac-68b3dca9cf85","slug":"thymulin","display_name":"Thymulin","entity_type_key":"peptide"},"object":{"id":"882dde28-b217-5440-ae75-965a97601b79","slug":"mouse-nfkb-il6-reporter","display_name":"Mouse Il6 promoter NF-kappa-B reporter response","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6b4a9b11-284c-5285-b818-c3efc2493b6a","stable_key":"18100170-a014-51c3-adeb-9dab4162b8cc:aged-il6-site-event","event_type":"experimental_observation","label":"Mutation of an NF-kappa-B site in the mouse Il6 reporter removed the inhibitory reporter effect of thymulin treatment.","description":"The 2026 Nature Communications study used **thymulin plus equimolar zinc versus zinc-matched controls**. Human PBMCs received 24-hour treatment before stimulated cytokine assessment. Mouse macrophages were conditioned during a week of differentiation, then challenged with LPS. Reduced IκBα phosphorylation, p65 DNA binding and inflammatory cytokine responses were reported. Mutation of an NF-κB site in an Il6 reporter removed the inhibitory reporter effect.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"23819462-9bdf-5856-beac-68b3dca9cf85","slug":"thymulin","display_name":"Thymulin","entity_type_key":"peptide"},"role":"tested factor","stoichiometry":null,"state_label":"Thymulin plus equimolar zinc","sequence_order":0,"notes":""},{"entity":{"id":"882dde28-b217-5440-ae75-965a97601b79","slug":"mouse-nfkb-il6-reporter","display_name":"Mouse Il6 promoter NF-kappa-B reporter response","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"mixed","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Full text obtained; relevant results/methods inspected. This does not assert exhaustive figure/data reanalysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"peptide exposure","comparator":"Zinc-matched control","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"thymulin","display_name":"Thymulin","entity_type_key":"peptide"}},{"dimension":"experimental_condition","value_text":"equimolar zinc","comparator":"Zinc-matched control","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Thymulin plus equimolar zinc\", \"comparator\": \"Zinc-matched control\", \"endpoint\": \"Mutation of an NF-kappa-B site in the mouse Il6 reporter removed the inhibitory reporter effect of thymulin treatment.\", \"effect_direction\": \"mixed\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"thymulin\", \"state\": \"peptide exposure\"}, {\"entity_slug\": \"zinc-ion\", \"state\": \"equimolar zinc\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse macrophages conditioned for one week, then challenged with LPS; human PBMC experiments used 24-hour pretreatment and are separate.","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":"Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Mutation of an NF-kappa-B site in the mouse Il6 reporter removed the inhibitory reporter effect of thymulin treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy. | 2026 | DOI 10.1038/s41467-026-75383-0 | PMID 42481458 | https://www.nature.com/articles/s41467-026-75383-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 78-78; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"366a945b-833f-5c4c-8509-a1d82067f5b4","evidence_kind":"source_excerpt","locator":"Lines 78-78","start_line":78,"end_line":78,"excerpt":"The 2026 Nature Communications study used **thymulin plus equimolar zinc versus zinc-matched controls**. Human PBMCs received 24-hour treatment before stimulated cytokine assessment. Mouse macrophages were conditioned during a week of differentiation, then challenged with LPS. Reduced IκBα phosphorylation, p65 DNA binding and inflammatory cytokine responses were reported. Mutation of an NF-κB site in an Il6 reporter removed the inhibitory reporter effect.","model_system":"Mouse macrophages conditioned for one week, then challenged with LPS; human PBMC experiments used 24-hour pretreatment and are separate.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e1871d49-9c6b-547b-a1bb-6e2b9270ca89","stable_key":"import-18100170-a014-51c3-adeb-9dab4162b8cc","title":"Thymulin: detailed mechanisms of action (reviewed 3 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"6e8ed0d7a5e23fc822f2ab418e0c4fb2411c01fcaa330039e8d7d93218cacc88","revision_id":"8c0e3449-9bbd-57c0-bb5e-de83f044f2ac","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}