{"id":"ad4ebf2e-662d-59e7-bb6f-d792b87ae007","stable_key":"773f772e-bf8e-5e52-a2a2-6dd694d67f5d:bromelain-e64-dependence","predicate":"prevents_bromelain_effect_on","statement":"E64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9b6cc032-1059-56fe-8588-87c7a4251105","mechanism_event_label":"E64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.","subject":{"id":"9b4a9c30-6e88-5624-afd4-6bd48023eb73","slug":"e64-cysteine-protease-inhibitor","display_name":"E64 cysteine-protease inhibitor","entity_type_key":"drug"},"object":{"id":"4d639537-19f6-51d0-984d-c58db2e3f1d2","slug":"human-cd25","display_name":"Human interleukin-2 receptor alpha / CD25","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9b6cc032-1059-56fe-8588-87c7a4251105","stable_key":"773f772e-bf8e-5e52-a2a2-6dd694d67f5d:bromelain-e64-dependence-event","event_type":"observed_relationship","label":"E64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.","description":"E64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9b4a9c30-6e88-5624-afd4-6bd48023eb73","slug":"e64-cysteine-protease-inhibitor","display_name":"E64 cysteine-protease inhibitor","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4d639537-19f6-51d0-984d-c58db2e3f1d2","slug":"human-cd25","display_name":"Human interleukin-2 receptor alpha / CD25","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6a3990e6-85af-58c7-8087-8a251db842fa","slug":"bromelain","display_name":"Bromelain","entity_type_key":"peptide"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"dose","value_text":"E64 with bromelain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Up to 8 hours","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; model-specific source-derived curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Anti-CD3-activated human CD4 T cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"E64 is an experimental inhibitor; this is a mechanism control, not a treatment comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Bromelain chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings.","comparator":null,"unit":null,"notes":"","entity":{"slug":"bromelain","display_name":"Bromelain","entity_type_key":"peptide"}},{"dimension":"organism","value_text":"Anti-CD3-activated human CD4 T cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"E64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro. (2009). https://pubmed.ncbi.nlm.nih.gov/19162239/ DOI: 10.1016/j.intimp.2008.12.012","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro co-exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Protease-dependence control","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"74ab9ad7-4ad7-5c48-83c7-982d5e62eee9","evidence_kind":"source_excerpt","locator":"Lines 66-75","start_line":66,"end_line":75,"excerpt":"## bromelain-e64-dependence\nE64 prevented the bromelain-associated reduction of CD25, showing that the effect required cysteine-protease activity under these conditions.\nModel/species: Anti-CD3-activated human CD4 T cells\nTissue/system: Protease-dependence control\nExposure: E64 with bromelain\nRoute: In vitro co-exposure\nDuration: Up to 8 hours\nLimits: E64 is an experimental inhibitor; this is a mechanism control, not a treatment comparison.\nPrimary reference: Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro. (2009). https://pubmed.ncbi.nlm.nih.gov/19162239/ DOI: 10.1016/j.intimp.2008.12.012\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"Anti-CD3-activated human CD4 T cells","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span with primary citation; not a publisher quotation.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9d363b4e-f438-5664-9d74-99c2e359391d","stable_key":"import-773f772e-bf8e-5e52-a2a2-6dd694d67f5d","title":"Bromelain: mechanism of action and interactions (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text.","file_path":"","sha256":"b328dbb8082bea612bb2c40d6ff41fa670f6e62f714bd014c90627fcab86e95b","revision_id":"1c10d22e-ecdf-56ef-b820-bb21182a9577","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}