{"id":"0069b7a1-59b2-564d-927d-80a0aa62a36e","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-tnf-neutralization-nfkb","predicate":"neutralization-reduces","statement":"A TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"0172b60f-89d1-5d24-9a3a-3d9ae7251481","mechanism_event_label":"Blocking TNF signaling interrupted an inflammatory response in the cultured cells.","subject":{"id":"d7c0d1fc-7ce9-54f3-9f68-8313469e97b1","slug":"rat-tnf","display_name":"Rat tumor necrosis factor alpha / Tnf","entity_type_key":"cytokine"},"object":{"id":"875a94da-1eee-50d2-b5c1-e4316c2a8f45","slug":"nf-kappab-signaling","display_name":"NF-kappa-B signaling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0172b60f-89d1-5d24-9a3a-3d9ae7251481","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-tnf-neutralization-nfkb-event","event_type":"biochemical_relationship","label":"Blocking TNF signaling interrupted an inflammatory response in the cultured cells.","description":"A TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"disrupted nutrient supply","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d7c0d1fc-7ce9-54f3-9f68-8313469e97b1","slug":"rat-tnf","display_name":"Rat tumor necrosis factor alpha / Tnf","entity_type_key":"cytokine"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"875a94da-1eee-50d2-b5c1-e4316c2a8f45","slug":"nf-kappab-signaling","display_name":"NF-kappa-B signaling","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_location","value_text":"Abstract; TNF-alpha neutralization experiment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"blocked the increased NF-κB activation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Rattus norvegicus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Blocking TNF signaling interrupted an inflammatory response in the cultured cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cultured astrocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1a674595-1901-512d-a5f9-84f3f21eb484","evidence_kind":"source_excerpt","locator":"Lines 1311-1323","start_line":1311,"end_line":1323,"excerpt":"### thiamine-def-tnf-neutralization-nfkb\nA TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments.\nCondition category: nutrient_deficiency\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Blocking TNF signaling interrupted an inflammatory response in the cultured cells.\norganism: Rattus norvegicus\ntissue_or_cell_type: Cultured astrocytes\nexperimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.\nlimitations: An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect.\nevidence_location: Abstract; TNF-alpha neutralization experiment\nevidence_span: blocked the increased NF-κB activation\nexposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes\n[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. 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