PubMed:27344344 JSONTXT

{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":113},"obj":"Sentence"},{"id":"T2","span":{"begin":114,"end":247},"obj":"Sentence"},{"id":"T3","span":{"begin":248,"end":445},"obj":"Sentence"},{"id":"T4","span":{"begin":446,"end":525},"obj":"Sentence"},{"id":"T5","span":{"begin":526,"end":630},"obj":"Sentence"},{"id":"T6","span":{"begin":631,"end":798},"obj":"Sentence"},{"id":"T7","span":{"begin":799,"end":968},"obj":"Sentence"},{"id":"T8","span":{"begin":969,"end":1102},"obj":"Sentence"},{"id":"T9","span":{"begin":1103,"end":1274},"obj":"Sentence"},{"id":"T10","span":{"begin":1275,"end":1419},"obj":"Sentence"},{"id":"T11","span":{"begin":1420,"end":1582},"obj":"Sentence"},{"id":"T12","span":{"begin":1583,"end":1679},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":113},"obj":"Sentence"},{"id":"T2","span":{"begin":114,"end":247},"obj":"Sentence"},{"id":"T3","span":{"begin":248,"end":445},"obj":"Sentence"},{"id":"T4","span":{"begin":446,"end":525},"obj":"Sentence"},{"id":"T5","span":{"begin":526,"end":630},"obj":"Sentence"},{"id":"T6","span":{"begin":631,"end":798},"obj":"Sentence"},{"id":"T7","span":{"begin":799,"end":968},"obj":"Sentence"},{"id":"T8","span":{"begin":969,"end":1102},"obj":"Sentence"},{"id":"T9","span":{"begin":1103,"end":1274},"obj":"Sentence"},{"id":"T10","span":{"begin":1275,"end":1419},"obj":"Sentence"},{"id":"T11","span":{"begin":1420,"end":1582},"obj":"Sentence"},{"id":"T12","span":{"begin":1583,"end":1679},"obj":"Sentence"}],"text":"Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.\nPerfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mechanistic analysis. UPLC-ESI-QTOFMS-based metabolomics was used to explore the contributing components of the serum metabolome that led to variation between wild-type and Pparα-null mice. Bile acid homeostasis was disrupted, and slight hepatocyte injury in wild-type mice accompanied by adaptive regulation of bile acid synthesis and transport was observed. The serum metabolome in wild-type clustered differently from that in Pparα-null, featured by sharp increases in bile acid components. Differential toxicokinetic tendency was supported by regulation of UDP-glucuronosyltransferases dependent on PPARα, but it did not contribute to the hepatotoxic responses. Increase in Il-10 and activation of the JNK pathway indicated inflammation was induced by disruption of bile acid homeostasis in wild-type mice. Inhibition of p-p65 dependent on PPARα activation by PFDA stopped the inflammatory cascade, as indicated by negative response of Il-6, Tnf-α, and STAT3 signaling. These data suggest disruptive and protective role of PPARα in hepatic responses induced by PFDA."}

{"project":"Wangshuguang","denotations":[{"id":"T1","span":{"begin":114,"end":131},"obj":"I-Variation"},{"id":"T2","span":{"begin":132,"end":136},"obj":"I-Variation"},{"id":"T3","span":{"begin":370,"end":380},"obj":"B-Negative_Function"},{"id":"T4","span":{"begin":670,"end":674},"obj":"B-Regulation"},{"id":"T5","span":{"begin":675,"end":677},"obj":"I-Regulation"},{"id":"T6","span":{"begin":678,"end":685},"obj":"I-Regulation"},{"id":"T7","span":{"begin":743,"end":746},"obj":"B-Regulation"},{"id":"T8","span":{"begin":747,"end":749},"obj":"I-Regulation"},{"id":"T9","span":{"begin":898,"end":906},"obj":"B-Molecular_Activity"},{"id":"T10","span":{"begin":907,"end":917},"obj":"I-Molecular_Activity"},{"id":"T11","span":{"begin":926,"end":930},"obj":"B-Cell_Physiological_Activity"},{"id":"T12","span":{"begin":931,"end":940},"obj":"I-Cell_Physiological_Activity"},{"id":"T13","span":{"begin":1199,"end":1208},"obj":"B-Variation"},{"id":"T14","span":{"begin":1297,"end":1307},"obj":"B-Molecular_Activity"},{"id":"T15","span":{"begin":1319,"end":1326},"obj":"B-Molecular_Activity"},{"id":"T16","span":{"begin":1389,"end":1400},"obj":"B-Variation"},{"id":"T17","span":{"begin":1440,"end":1449},"obj":"B-Molecular_Activity"},{"id":"T18","span":{"begin":1459,"end":1469},"obj":"B-Molecular_Activity"},{"id":"T19","span":{"begin":1617,"end":1627},"obj":"B-Molecular_Activity"},{"id":"T20","span":{"begin":1628,"end":1632},"obj":"I-Molecular_Activity"}],"text":"Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.\nPerfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mechanistic analysis. UPLC-ESI-QTOFMS-based metabolomics was used to explore the contributing components of the serum metabolome that led to variation between wild-type and Pparα-null mice. Bile acid homeostasis was disrupted, and slight hepatocyte injury in wild-type mice accompanied by adaptive regulation of bile acid synthesis and transport was observed. The serum metabolome in wild-type clustered differently from that in Pparα-null, featured by sharp increases in bile acid components. Differential toxicokinetic tendency was supported by regulation of UDP-glucuronosyltransferases dependent on PPARα, but it did not contribute to the hepatotoxic responses. Increase in Il-10 and activation of the JNK pathway indicated inflammation was induced by disruption of bile acid homeostasis in wild-type mice. Inhibition of p-p65 dependent on PPARα activation by PFDA stopped the inflammatory cascade, as indicated by negative response of Il-6, Tnf-α, and STAT3 signaling. These data suggest disruptive and protective role of PPARα in hepatic responses induced by PFDA."}

{"project":"123123123","denotations":[{"id":"T1","span":{"begin":114,"end":131},"obj":"I-Variation"},{"id":"T2","span":{"begin":132,"end":136},"obj":"I-Variation"},{"id":"T3","span":{"begin":370,"end":380},"obj":"B-Negative_Function"},{"id":"T4","span":{"begin":670,"end":674},"obj":"B-Regulation"},{"id":"T5","span":{"begin":675,"end":677},"obj":"I-Regulation"},{"id":"T6","span":{"begin":678,"end":685},"obj":"I-Regulation"},{"id":"T7","span":{"begin":743,"end":746},"obj":"B-Regulation"},{"id":"T8","span":{"begin":747,"end":749},"obj":"I-Regulation"},{"id":"T9","span":{"begin":898,"end":906},"obj":"B-Molecular_Activity"},{"id":"T10","span":{"begin":907,"end":917},"obj":"I-Molecular_Activity"},{"id":"T11","span":{"begin":926,"end":930},"obj":"B-Cell_Physiological_Activity"},{"id":"T12","span":{"begin":931,"end":940},"obj":"I-Cell_Physiological_Activity"},{"id":"T13","span":{"begin":1199,"end":1208},"obj":"B-Variation"},{"id":"T14","span":{"begin":1297,"end":1307},"obj":"B-Molecular_Activity"},{"id":"T15","span":{"begin":1319,"end":1326},"obj":"B-Molecular_Activity"},{"id":"T16","span":{"begin":1389,"end":1400},"obj":"B-Variation"},{"id":"T17","span":{"begin":1440,"end":1449},"obj":"B-Molecular_Activity"},{"id":"T18","span":{"begin":1459,"end":1469},"obj":"B-Molecular_Activity"},{"id":"T19","span":{"begin":1617,"end":1627},"obj":"B-Molecular_Activity"},{"id":"T20","span":{"begin":1628,"end":1632},"obj":"I-Molecular_Activity"}],"text":"Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.\nPerfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mechanistic analysis. UPLC-ESI-QTOFMS-based metabolomics was used to explore the contributing components of the serum metabolome that led to variation between wild-type and Pparα-null mice. Bile acid homeostasis was disrupted, and slight hepatocyte injury in wild-type mice accompanied by adaptive regulation of bile acid synthesis and transport was observed. The serum metabolome in wild-type clustered differently from that in Pparα-null, featured by sharp increases in bile acid components. Differential toxicokinetic tendency was supported by regulation of UDP-glucuronosyltransferases dependent on PPARα, but it did not contribute to the hepatotoxic responses. Increase in Il-10 and activation of the JNK pathway indicated inflammation was induced by disruption of bile acid homeostasis in wild-type mice. Inhibition of p-p65 dependent on PPARα activation by PFDA stopped the inflammatory cascade, as indicated by negative response of Il-6, Tnf-α, and STAT3 signaling. These data suggest disruptive and protective role of PPARα in hepatic responses induced by PFDA."}