unikei/distilbert-base-re-punctuate
Token Classification
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Updated
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2.99k
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4
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list | coreferences
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|---|---|---|---|---|---|---|
17512723 | 17512723 | [
{
"id": "17512723_title",
"type": "title",
"text": [
"RDH12, a retinol dehydrogenase causing Leber's congenital amaurosis, is also involved in steroid metabolism."
],
"offsets": [
[
0,
108
]
]
},
{
"id": "17512723_abstract",
"type": "abstract",
"text": [
"Three retinol dehydrogenases (RDHs) were tested for steroid converting abilities: human and murine RDH 12 and human RDH13. RDH12 is involved in retinal degeneration in Leber's congenital amaurosis (LCA). We show that murine Rdh12 and human RDH13 do not reveal activity towards the checked steroids, but that human type 12 RDH reduces dihydrotestosterone to androstanediol, and is thus also involved in steroid metabolism. Furthermore, we analyzed both expression and subcellular localization of these enzymes."
],
"offsets": [
[
109,
618
]
]
}
] | [
{
"id": "17512723_T1",
"type": "CHEMICAL",
"text": [
"androstanediol"
],
"offsets": [
[
466,
480
]
],
"normalized": []
},
{
"id": "17512723_T2",
"type": "CHEMICAL",
"text": [
"retinol"
],
"offsets": [
[
115,
122
]
],
"normalized": []
},
{
"id": "17512723_T3",
"type": "CHEMICAL",
"text": [
"retinol"
],
"offsets": [
[
9,
16
]
],
"normalized": []
},
{
"id": "17512723_T4",
"type": "GENE-Y",
"text": [
"human RDH13"
],
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[
219,
230
]
],
"normalized": []
},
{
"id": "17512723_T5",
"type": "GENE-Y",
"text": [
"RDH12"
],
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[
232,
237
]
],
"normalized": []
},
{
"id": "17512723_T6",
"type": "GENE-Y",
"text": [
"murine Rdh12"
],
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[
326,
338
]
],
"normalized": []
},
{
"id": "17512723_T7",
"type": "GENE-Y",
"text": [
"human RDH13"
],
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[
343,
354
]
],
"normalized": []
},
{
"id": "17512723_T8",
"type": "GENE-N",
"text": [
"RDHs"
],
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[
139,
143
]
],
"normalized": []
},
{
"id": "17512723_T9",
"type": "GENE-Y",
"text": [
"human type 12 RDH"
],
"offsets": [
[
417,
434
]
],
"normalized": []
},
{
"id": "17512723_T10",
"type": "GENE-N",
"text": [
"retinol dehydrogenases"
],
"offsets": [
[
115,
137
]
],
"normalized": []
},
{
"id": "17512723_T11",
"type": "GENE-N",
"text": [
"human and murine RDH 12"
],
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[
191,
214
]
],
"normalized": []
},
{
"id": "17512723_T12",
"type": "GENE-Y",
"text": [
"RDH12"
],
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[
0,
5
]
],
"normalized": []
},
{
"id": "17512723_T13",
"type": "GENE-N",
"text": [
"retinol dehydrogenase"
],
"offsets": [
[
9,
30
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "17512723_0",
"type": "PRODUCT-OF",
"arg1_id": "17512723_T1",
"arg2_id": "17512723_T9",
"normalized": []
}
] |
23557993 | 23557993 | [
{
"id": "23557993_title",
"type": "title",
"text": [
"A diarylheptanoid phytoestrogen from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3-ol, accelerates human osteoblast proliferation and differentiation."
],
"offsets": [
[
0,
149
]
]
},
{
"id": "23557993_abstract",
"type": "abstract",
"text": [
"Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1-10μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10-100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10nM and, at 100nM, activated MAP kinase signaling within 30min. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10nM, and optimal response in most cases was at 100nM. At 7-21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women."
],
"offsets": [
[
150,
1872
]
]
}
] | [
{
"id": "23557993_T1",
"type": "CHEMICAL",
"text": [
"DPHD"
],
"offsets": [
[
1259,
1263
]
],
"normalized": []
},
{
"id": "23557993_T2",
"type": "CHEMICAL",
"text": [
"estrogen"
],
"offsets": [
[
1287,
1295
]
],
"normalized": []
},
{
"id": "23557993_T3",
"type": "CHEMICAL",
"text": [
"ICI182780"
],
"offsets": [
[
1316,
1325
]
],
"normalized": []
},
{
"id": "23557993_T4",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1351,
1355
]
],
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},
{
"id": "23557993_T5",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1452,
1456
]
],
"normalized": []
},
{
"id": "23557993_T6",
"type": "CHEMICAL",
"text": [
"17β-estradiol"
],
"offsets": [
[
1553,
1566
]
],
"normalized": []
},
{
"id": "23557993_T7",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1577,
1581
]
],
"normalized": []
},
{
"id": "23557993_T8",
"type": "CHEMICAL",
"text": [
"17β-estradiol"
],
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[
1683,
1696
]
],
"normalized": []
},
{
"id": "23557993_T9",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1715,
1719
]
],
"normalized": []
},
{
"id": "23557993_T10",
"type": "CHEMICAL",
"text": [
"diarylheptanoid"
],
"offsets": [
[
389,
404
]
],
"normalized": []
},
{
"id": "23557993_T11",
"type": "CHEMICAL",
"text": [
"(3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol"
],
"offsets": [
[
405,
449
]
],
"normalized": []
},
{
"id": "23557993_T12",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
451,
455
]
],
"normalized": []
},
{
"id": "23557993_T13",
"type": "CHEMICAL",
"text": [
"DPHD"
],
"offsets": [
[
521,
525
]
],
"normalized": []
},
{
"id": "23557993_T14",
"type": "CHEMICAL",
"text": [
"DPHD"
],
"offsets": [
[
604,
608
]
],
"normalized": []
},
{
"id": "23557993_T15",
"type": "CHEMICAL",
"text": [
"DPHD"
],
"offsets": [
[
711,
715
]
],
"normalized": []
},
{
"id": "23557993_T16",
"type": "CHEMICAL",
"text": [
"17β-estradiol"
],
"offsets": [
[
728,
741
]
],
"normalized": []
},
{
"id": "23557993_T17",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
830,
834
]
],
"normalized": []
},
{
"id": "23557993_T18",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
865,
869
]
],
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},
{
"id": "23557993_T19",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1025,
1029
]
],
"normalized": []
},
{
"id": "23557993_T20",
"type": "CHEMICAL",
"text": [
"DPHD"
],
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[
1119,
1123
]
],
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},
{
"id": "23557993_T21",
"type": "CHEMICAL",
"text": [
"diarylheptanoid"
],
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[
2,
17
]
],
"normalized": []
},
{
"id": "23557993_T22",
"type": "CHEMICAL",
"text": [
"1,7-diphenyl-4,6-heptadien-3-ol"
],
"offsets": [
[
53,
84
]
],
"normalized": []
},
{
"id": "23557993_T23",
"type": "GENE-N",
"text": [
"alkaline phosphatase"
],
"offsets": [
[
1177,
1197
]
],
"normalized": []
},
{
"id": "23557993_T24",
"type": "GENE-Y",
"text": [
"estrogen receptor"
],
"offsets": [
[
1287,
1304
]
],
"normalized": []
},
{
"id": "23557993_T25",
"type": "GENE-Y",
"text": [
"RUNX2"
],
"offsets": [
[
1419,
1424
]
],
"normalized": []
},
{
"id": "23557993_T26",
"type": "GENE-Y",
"text": [
"osterix"
],
"offsets": [
[
1429,
1436
]
],
"normalized": []
},
{
"id": "23557993_T27",
"type": "GENE-Y",
"text": [
"COL1A1"
],
"offsets": [
[
1516,
1522
]
],
"normalized": []
},
{
"id": "23557993_T28",
"type": "GENE-Y",
"text": [
"osteocalcin"
],
"offsets": [
[
1527,
1538
]
],
"normalized": []
},
{
"id": "23557993_T29",
"type": "GENE-Y",
"text": [
"osteoprotegerin"
],
"offsets": [
[
1596,
1611
]
],
"normalized": []
},
{
"id": "23557993_T30",
"type": "GENE-Y",
"text": [
"RANKL"
],
"offsets": [
[
1615,
1620
]
],
"normalized": []
},
{
"id": "23557993_T31",
"type": "GENE-N",
"text": [
"MAP kinase"
],
"offsets": [
[
932,
942
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23557993_0",
"type": "ANTAGONIST",
"arg1_id": "23557993_T3",
"arg2_id": "23557993_T24",
"normalized": []
},
{
"id": "23557993_1",
"type": "ACTIVATOR",
"arg1_id": "23557993_T18",
"arg2_id": "23557993_T31",
"normalized": []
},
{
"id": "23557993_2",
"type": "ACTIVATOR",
"arg1_id": "23557993_T1",
"arg2_id": "23557993_T24",
"normalized": []
},
{
"id": "23557993_3",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23557993_T4",
"arg2_id": "23557993_T25",
"normalized": []
},
{
"id": "23557993_4",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23557993_T4",
"arg2_id": "23557993_T26",
"normalized": []
},
{
"id": "23557993_5",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23557993_T5",
"arg2_id": "23557993_T27",
"normalized": []
},
{
"id": "23557993_6",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23557993_T5",
"arg2_id": "23557993_T28",
"normalized": []
}
] |
23161873 | 23161873 | [
{
"id": "23161873_title",
"type": "title",
"text": [
"The role of the carbohydrate response element-binding protein in male fructose-fed rats."
],
"offsets": [
[
0,
88
]
]
},
{
"id": "23161873_abstract",
"type": "abstract",
"text": [
"By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP is a potential therapeutic target, we decreased hepatic expression of ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley rats fed either a high-fructose or high-fat diet. ChREBP ASO treatment decreased plasma triglyceride concentrations compared with control ASO treatment in both diet groups. The reduction was more pronounced in the fructose-fed group and attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a decrease in the rate of hepatic triglyceride secretion. This was associated with an increase in insulin-stimulated peripheral glucose uptake, as assessed by the hyperinsulinemic-euglycemic clamp. In contrast, ChREBP ASO did not alter hepatic lipid content or hepatic insulin sensitivity. Interestingly, fructose-fed rats treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and aspartate aminotransferase concentrations. This was associated with decreased expression of fructose aldolase and fructokinase, reminiscent of inherited disorders of fructose metabolism. In summary, these studies suggest that targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without the improvements in hepatic steatosis and hepatic insulin responsiveness."
],
"offsets": [
[
89,
1809
]
]
}
] | [
{
"id": "23161873_T1",
"type": "CHEMICAL",
"text": [
"glucose"
],
"offsets": [
[
1154,
1161
]
],
"normalized": []
},
{
"id": "23161873_T2",
"type": "CHEMICAL",
"text": [
"fructose"
],
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[
1331,
1339
]
],
"normalized": []
},
{
"id": "23161873_T3",
"type": "CHEMICAL",
"text": [
"uric acid"
],
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[
1394,
1403
]
],
"normalized": []
},
{
"id": "23161873_T4",
"type": "CHEMICAL",
"text": [
"alanine"
],
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[
1405,
1412
]
],
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},
{
"id": "23161873_T5",
"type": "CHEMICAL",
"text": [
"aspartate"
],
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[
1431,
1440
]
],
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},
{
"id": "23161873_T6",
"type": "CHEMICAL",
"text": [
"fructose"
],
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[
1523,
1531
]
],
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},
{
"id": "23161873_T7",
"type": "CHEMICAL",
"text": [
"fructose"
],
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[
1597,
1605
]
],
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},
{
"id": "23161873_T8",
"type": "CHEMICAL",
"text": [
"fructose"
],
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[
1686,
1694
]
],
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},
{
"id": "23161873_T9",
"type": "CHEMICAL",
"text": [
"sugar"
],
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[
295,
300
]
],
"normalized": []
},
{
"id": "23161873_T10",
"type": "CHEMICAL",
"text": [
"monosaccharides"
],
"offsets": [
[
381,
396
]
],
"normalized": []
},
{
"id": "23161873_T11",
"type": "CHEMICAL",
"text": [
"carbohydrate"
],
"offsets": [
[
481,
493
]
],
"normalized": []
},
{
"id": "23161873_T12",
"type": "CHEMICAL",
"text": [
"fructose"
],
"offsets": [
[
736,
744
]
],
"normalized": []
},
{
"id": "23161873_T13",
"type": "CHEMICAL",
"text": [
"triglyceride"
],
"offsets": [
[
801,
813
]
],
"normalized": []
},
{
"id": "23161873_T14",
"type": "CHEMICAL",
"text": [
"fructose"
],
"offsets": [
[
927,
935
]
],
"normalized": []
},
{
"id": "23161873_T15",
"type": "CHEMICAL",
"text": [
"triglyceride"
],
"offsets": [
[
1060,
1072
]
],
"normalized": []
},
{
"id": "23161873_T16",
"type": "CHEMICAL",
"text": [
"carbohydrate"
],
"offsets": [
[
16,
28
]
],
"normalized": []
},
{
"id": "23161873_T17",
"type": "CHEMICAL",
"text": [
"fructose"
],
"offsets": [
[
70,
78
]
],
"normalized": []
},
{
"id": "23161873_T18",
"type": "GENE-N",
"text": [
"insulin"
],
"offsets": [
[
1124,
1131
]
],
"normalized": []
},
{
"id": "23161873_T19",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
1237,
1243
]
],
"normalized": []
},
{
"id": "23161873_T20",
"type": "GENE-N",
"text": [
"insulin"
],
"offsets": [
[
1295,
1302
]
],
"normalized": []
},
{
"id": "23161873_T21",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
1362,
1368
]
],
"normalized": []
},
{
"id": "23161873_T22",
"type": "GENE-N",
"text": [
"alanine transaminase"
],
"offsets": [
[
1405,
1425
]
],
"normalized": []
},
{
"id": "23161873_T23",
"type": "GENE-N",
"text": [
"aspartate aminotransferase"
],
"offsets": [
[
1431,
1457
]
],
"normalized": []
},
{
"id": "23161873_T24",
"type": "GENE-N",
"text": [
"fructose aldolase"
],
"offsets": [
[
1523,
1540
]
],
"normalized": []
},
{
"id": "23161873_T25",
"type": "GENE-Y",
"text": [
"fructokinase"
],
"offsets": [
[
1545,
1557
]
],
"normalized": []
},
{
"id": "23161873_T26",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
1667,
1673
]
],
"normalized": []
},
{
"id": "23161873_T27",
"type": "GENE-N",
"text": [
"insulin"
],
"offsets": [
[
1786,
1793
]
],
"normalized": []
},
{
"id": "23161873_T28",
"type": "GENE-Y",
"text": [
"carbohydrate response element-binding protein"
],
"offsets": [
[
481,
526
]
],
"normalized": []
},
{
"id": "23161873_T29",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
528,
534
]
],
"normalized": []
},
{
"id": "23161873_T30",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
558,
564
]
],
"normalized": []
},
{
"id": "23161873_T31",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
635,
641
]
],
"normalized": []
},
{
"id": "23161873_T32",
"type": "GENE-Y",
"text": [
"ChREBP"
],
"offsets": [
[
763,
769
]
],
"normalized": []
},
{
"id": "23161873_T33",
"type": "GENE-Y",
"text": [
"ACC2"
],
"offsets": [
[
996,
1000
]
],
"normalized": []
},
{
"id": "23161873_T34",
"type": "GENE-Y",
"text": [
"FAS"
],
"offsets": [
[
1002,
1005
]
],
"normalized": []
},
{
"id": "23161873_T35",
"type": "GENE-Y",
"text": [
"SCD1"
],
"offsets": [
[
1007,
1011
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],
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]
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}
] | [] | [] | [
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"id": "23161873_5",
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}
] |
17292977 | 17292977 | [
{
"id": "17292977_title",
"type": "title",
"text": [
"Biological activity of AC3174, a peptide analog of exendin-4."
],
"offsets": [
[
0,
61
]
]
},
{
"id": "17292977_abstract",
"type": "abstract",
"text": [
"Exenatide, the active ingredient of BYETTA (exenatide injection), is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. Exenatide binds to and activates the known GLP-1 receptor with a potency comparable to that of the mammalian incretin GLP-1(7-36), thereby acting as a glucoregulatory agent. AC3174 is an analog of exenatide with leucine substituted for methionine at position 14, [Leu(14)]exendin-4. The purpose of these studies was to evaluate the glucoregulatory activity and pharmacokinetics of AC3174. In RINm5f cell membranes, the potency of AC3174 for the displacement of [(125)I]GLP-1 and activation of adenylate cyclase was similar to that of exenatide and GLP-1. In vivo, AC3174, administered as a single IP injection, significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge in both non-diabetic (C57BL/6) and diabetic db/db mice (P<0.05 vs. vehicle-treated). The magnitude of glucose lowering of AC3174 was comparable to exenatide. The ED(50) values of AC3174 for glucose lowering (60 minute post-dose) were 1.2 microg/kg in db/db mice and 1.3 microg/kg in C57BL/6 mice. AC3174 has insulinotropic activity in vivo. Administration of AC3174 resulted in a 4-fold increase in insulin concentrations in normal mice following an IP glucose challenge. AC3174 was also shown to inhibit food intake and decrease gastric emptying in rodent models. AC3174 was stable in human plasma (>90% of parent peptide was present after 5 h of incubation). In rats, the in vivo half-life of AC3174 was 42-43 min following SC administration. In summary, AC3174 is an analog of exenatide that binds to the GLP-1 receptor in vitro and shares many of the biological and glucoregulatory activities of exenatide and GLP-1 in vivo."
],
"offsets": [
[
62,
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]
]
}
] | [
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"glucose"
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]
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"id": "17292977_T2",
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"glucose"
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"glucose"
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]
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{
"id": "17292977_T4",
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"leucine"
],
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439,
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]
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"methionine"
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463,
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]
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"(125)I"
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720,
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]
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]
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"glucose"
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"glucose"
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]
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},
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"id": "17292977_T11",
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"text": [
"insulin"
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]
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"id": "17292977_T12",
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"GLP-1 receptor"
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"GLP-1(7-36)"
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720,
737
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"incretin"
],
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134,
142
]
],
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}
] | [] | [] | [
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"id": "17292977_0",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "17292977_T3",
"arg2_id": "17292977_T11",
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}
] |
23348500 | 23348500 | [
{
"id": "23348500_title",
"type": "title",
"text": [
"A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling."
],
"offsets": [
[
0,
139
]
]
},
{
"id": "23348500_abstract",
"type": "abstract",
"text": [
"Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term potentiation (LTP), which is thought to be involved in cognition. Multiple mGlu5-positive allosteric modulators (PAMs) have been developed from a variety of different scaffolds. Previous work has extensively characterized a common allosteric site on mGlu5, termed the MPEP (2-Methyl-6-(phenylethynyl)pyridine) binding site. However, one mGlu5 PAM, CPPHA (N-(4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl)-2-hydroxybenzamide), interacts with a separate allosteric site on mGlu5. Using cell-based assays and brain slice preparations, we characterized the interaction of a potent and efficacious mGlu5 PAM from the CPPHA series termed NCFP (N-(4-chloro-2-((4-fluoro-1,3-dioxoisoindolin-2-yl)methyl)phenyl)picolinamide). NCFP binds to the CPPHA site on mGlu5 and potentiates mGlu5-mediated responses in both recombinant and native systems. However, NCFP provides greater mGlu5 subtype selectivity than does CPPHA, making it more suitable for studies of effects on mGlu5 in CNS preparations. Of interest, NCFP does not potentiate responses involved in hippocampal synaptic plasticity (LTD/LTP), setting it apart from other previously characterized MPEP site PAMs. This suggests that although mGlu5 PAMs may have similar responses in some systems, they can induce differential effects on mGlu5-mediated physiologic responses in the CNS. Such stimulus bias by mGlu5 PAMs may complicate drug discovery efforts but would also allow for specifically tailored therapies, if pharmacological biases can be attributed to different therapeutic outcomes."
],
"offsets": [
[
140,
2013
]
]
}
] | [
{
"id": "23348500_T1",
"type": "CHEMICAL",
"text": [
"NCFP"
],
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[
1192,
1196
]
],
"normalized": []
},
{
"id": "23348500_T2",
"type": "CHEMICAL",
"text": [
"CPPHA"
],
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[
1210,
1215
]
],
"normalized": []
},
{
"id": "23348500_T3",
"type": "CHEMICAL",
"text": [
"NCFP"
],
"offsets": [
[
1320,
1324
]
],
"normalized": []
},
{
"id": "23348500_T4",
"type": "CHEMICAL",
"text": [
"CPPHA"
],
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[
1378,
1383
]
],
"normalized": []
},
{
"id": "23348500_T5",
"type": "CHEMICAL",
"text": [
"glutamate"
],
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[
153,
162
]
],
"normalized": []
},
{
"id": "23348500_T6",
"type": "CHEMICAL",
"text": [
"NCFP"
],
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[
1475,
1479
]
],
"normalized": []
},
{
"id": "23348500_T7",
"type": "CHEMICAL",
"text": [
"MPEP"
],
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[
1618,
1622
]
],
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},
{
"id": "23348500_T8",
"type": "CHEMICAL",
"text": [
"MPEP"
],
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723,
727
]
],
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},
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"id": "23348500_T9",
"type": "CHEMICAL",
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"2-Methyl-6-(phenylethynyl)pyridine"
],
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729,
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]
],
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},
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"id": "23348500_T10",
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"text": [
"CPPHA"
],
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803,
808
]
],
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},
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"id": "23348500_T11",
"type": "CHEMICAL",
"text": [
"N-(4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl)-2-hydroxybenzamide"
],
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[
810,
898
]
],
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},
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"id": "23348500_T12",
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"CPPHA"
],
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1087,
1092
]
],
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},
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"id": "23348500_T13",
"type": "CHEMICAL",
"text": [
"NCFP"
],
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[
1107,
1111
]
],
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},
{
"id": "23348500_T14",
"type": "CHEMICAL",
"text": [
"N-(4-chloro-2-((4-fluoro-1,3-dioxoisoindolin-2-yl)methyl)phenyl)picolinamide"
],
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[
1113,
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]
],
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},
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"id": "23348500_T15",
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"glutamate"
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21,
30
]
],
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},
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"id": "23348500_T16",
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"Metabotropic glutamate receptor 5"
],
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140,
173
]
],
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},
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"id": "23348500_T17",
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"mGlu5"
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1224,
1229
]
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"mGlu5"
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1246,
1251
]
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"mGlu5"
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1342,
1347
]
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1435,
1440
]
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1662,
1667
]
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1757,
1762
]
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},
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1828,
1833
]
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},
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315,
320
]
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},
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175,
180
]
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"id": "23348500_T26",
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530,
535
]
],
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},
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"mGlu5"
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705,
710
]
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]
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},
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946,
951
]
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},
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"id": "23348500_T30",
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"mGlu5"
],
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[
1068,
1073
]
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},
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"id": "23348500_T31",
"type": "GENE-Y",
"text": [
"mGlu5"
],
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[
123,
128
]
],
"normalized": []
},
{
"id": "23348500_T32",
"type": "GENE-Y",
"text": [
"metabotropic glutamate receptor 5"
],
"offsets": [
[
8,
41
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23348500_0",
"type": "PART-OF",
"arg1_id": "23348500_T8",
"arg2_id": "23348500_T27",
"normalized": []
},
{
"id": "23348500_1",
"type": "PART-OF",
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"arg2_id": "23348500_T27",
"normalized": []
},
{
"id": "23348500_2",
"type": "DIRECT-REGULATOR",
"arg1_id": "23348500_T11",
"arg2_id": "23348500_T29",
"normalized": []
},
{
"id": "23348500_3",
"type": "DIRECT-REGULATOR",
"arg1_id": "23348500_T10",
"arg2_id": "23348500_T29",
"normalized": []
},
{
"id": "23348500_4",
"type": "DIRECT-REGULATOR",
"arg1_id": "23348500_T1",
"arg2_id": "23348500_T17",
"normalized": []
},
{
"id": "23348500_5",
"type": "ACTIVATOR",
"arg1_id": "23348500_T1",
"arg2_id": "23348500_T18",
"normalized": []
}
] |
7828655 | 7828655 | [
{
"id": "7828655_title",
"type": "title",
"text": [
"Dopamine receptor blockade increases dopamine D2 receptor and glutamic acid decarboxylase mRNAs in mouse substantia nigra."
],
"offsets": [
[
0,
122
]
]
},
{
"id": "7828655_abstract",
"type": "abstract",
"text": [
"To study the influence of dopaminergic activity on the expression of dopamine D2 receptors and glutamic acid decarboxylase in substantia nigra, mice were treated daily for several days with an irreversibly acting dopamine D1 and dopamine D2 receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or with a selective irreversible D2 dopamine receptor antagonist fluphenazine-N-mustard. Mice were killed 24 h after the last injection. Dopamine D1 and dopamine D2 receptors were determined by receptor autoradiography, and dopamine D1 and dopamine D2 receptor mRNA and glutamic acid decarboxylase mRNA were determined by in situ hybridization histochemistry. The results showed that treatment with EEDQ, which blocked 80% to 85% of the dopamine D2 and dopamine D1 receptors in substantia nigra, increased the levels of dopamine D2 receptor mRNA in substantia nigra by about 27%. Treatment with fluphenazine-N-mustard, which blocked about 85% of the dopamine D2 receptors in substantia nigra but had no significant effect on dopamine D1 receptors, increased the levels of dopamine D2 receptor mRNA by about 34%. There were no detectable levels of dopamine D1 receptors, increased the levels of dopamine D2 receptor mRNA by about 34%. There were no detectable levels of dopamine D1 receptor mRNA in substantia nigra either in control animals or in animals treated with the dopamine receptor antagonists. Glutamic acid decarboxylase mRNA was expressed in several regions of the mid-brain but only that expressed in substantia nigra was altered by treatment with dopamine receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)"
],
"offsets": [
[
123,
1761
]
]
}
] | [
{
"id": "7828655_T1",
"type": "CHEMICAL",
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"dopamine"
],
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[
1163,
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]
],
"normalized": []
},
{
"id": "7828655_T2",
"type": "CHEMICAL",
"text": [
"dopamine"
],
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[
1210,
1218
]
],
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},
{
"id": "7828655_T3",
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"text": [
"dopamine"
],
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[
1285,
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]
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"id": "7828655_T4",
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"dopamine"
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[
1332,
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]
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"id": "7828655_T5",
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"dopamine"
],
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1407,
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]
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"id": "7828655_T6",
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"dopamine"
],
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1510,
1518
]
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},
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"id": "7828655_T7",
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"text": [
"Glutamic acid"
],
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[
1541,
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]
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},
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"id": "7828655_T8",
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"dopamine"
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]
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"id": "7828655_T9",
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"dopamine"
],
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336,
344
]
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},
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"id": "7828655_T10",
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"dopamine"
],
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[
352,
360
]
],
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},
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"id": "7828655_T11",
"type": "CHEMICAL",
"text": [
"N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline"
],
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[
384,
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]
],
"normalized": []
},
{
"id": "7828655_T12",
"type": "CHEMICAL",
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"EEDQ"
],
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[
432,
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]
],
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},
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"id": "7828655_T13",
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"text": [
"dopamine"
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474,
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] |
15456329 | 15456329 | [
{
"id": "15456329_title",
"type": "title",
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"Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis."
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"id": "15456329_abstract",
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"text": [
"Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date."
],
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]
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]
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]
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]
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"Nabumetone"
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0,
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]
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"COX"
],
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1350,
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]
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},
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"id": "15456329_T29",
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"COX"
],
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1877,
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]
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},
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"id": "15456329_T30",
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"text": [
"COX"
],
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[
1987,
1990
]
],
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},
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"id": "15456329_T31",
"type": "GENE-Y",
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"COX-2"
],
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[
2202,
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]
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},
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"COX"
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2274,
2277
]
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"COX-1"
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2390,
2395
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"COX-2"
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2396,
2401
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"COX-2"
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2669,
2674
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"cyclo-oxygenase (COX)-2"
],
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481,
504
]
],
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}
] | [] | [] | [
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}
] |
17258485 | 17258485 | [
{
"id": "17258485_title",
"type": "title",
"text": [
"Vitamin C transport and SVCT1 transporter expression in chick renal proximal tubule cells in culture."
],
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0,
101
]
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},
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"id": "17258485_abstract",
"type": "abstract",
"text": [
"The characteristics of vitamin C (ascorbic acid, ASC) transport were studied in polarized cultured monolayers of the chick (Gallus gallus) renal proximal tubule in Ussing chambers. Under voltage clamp conditions, monolayers responded to apical addition of ASC in a dose-dependent manner, with positive short circuit currents (I(SC)), ranging from 3 microA/cm(2) at 5 microM ASC to a maximal response of 27 microA/cm(2) at 200 microM, and a half-maximal response at 40 microM. There was no effect of basolateral addition of ASC, indicating a polarized transport process. The oxidized form of ASC, dehydroascorbic acid had negligible effects. The I(SC) response to ASC was completely eliminated with Na(+) ion replacement, and was also eliminated by bilateral reduction of bath Cl(-), from 137 to 2.6 mM. There was significant inhibition of the I(SC) responses to 30 microM ASC by the flavanoid quercetin (50 microM) and by 100 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-ethylisopropylamiloride (EIPA), blockers of anion exchangers and sodium-proton exchangers, respectively. There was no inhibition, however, by the chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB). Phorbol 12-myristate 13 acetate (PMA), the phorbol ester activator of protein kinase C, caused a 37% decrease in the I(SC) response to ASC. Chicken-specific primers to an EST homolog of the human vitamin C transporter SVCT1 (SLC23A1) were designed and used to probe transporter expression in these cells. RT-PCR analysis demonstrated the presence of chicken SVCT1 in both cultured cells and in freshly isolated proximal tubule fragments. These data indicate the presence of an electrogenic, sodium-dependent vitamin C transporter (SVCT1) in the chick renal proximal tubule. Vitamin C transport and conservation by the kidney is likely to be especially critical in birds, due to high plasma glucose levels and resulting high levels of reactive oxygen species."
],
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[
102,
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]
}
] | [
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1122,
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"id": "17258485_T2",
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"sodium"
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1162,
1168
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1243,
1251
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"id": "17258485_T4",
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1268,
1310
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"id": "17258485_T5",
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1312,
1316
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"id": "17258485_T6",
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"Phorbol 12-myristate 13 acetate"
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1319,
1350
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"id": "17258485_T7",
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1352,
1355
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[
1362,
1375
]
],
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{
"id": "17258485_T9",
"type": "CHEMICAL",
"text": [
"ASC"
],
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[
1454,
1457
]
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{
"id": "17258485_T10",
"type": "CHEMICAL",
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"vitamin C"
],
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[
1515,
1524
]
],
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},
{
"id": "17258485_T11",
"type": "CHEMICAL",
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"sodium"
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1810,
1816
]
],
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},
{
"id": "17258485_T12",
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"text": [
"vitamin C"
],
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1827,
1836
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],
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},
{
"id": "17258485_T13",
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"Vitamin C"
],
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[
1893,
1902
]
],
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},
{
"id": "17258485_T14",
"type": "CHEMICAL",
"text": [
"glucose"
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[
2009,
2016
]
],
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},
{
"id": "17258485_T15",
"type": "CHEMICAL",
"text": [
"oxygen"
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2062,
2068
]
],
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},
{
"id": "17258485_T16",
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"vitamin C"
],
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125,
134
]
],
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},
{
"id": "17258485_T17",
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"ascorbic acid"
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[
136,
149
]
],
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},
{
"id": "17258485_T18",
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"text": [
"ASC"
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476,
479
]
],
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},
{
"id": "17258485_T19",
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"text": [
"ASC"
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151,
154
]
],
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},
{
"id": "17258485_T20",
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"ASC"
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625,
628
]
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},
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"id": "17258485_T21",
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"ASC"
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693,
696
]
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},
{
"id": "17258485_T22",
"type": "CHEMICAL",
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"dehydroascorbic acid"
],
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[
698,
718
]
],
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},
{
"id": "17258485_T23",
"type": "CHEMICAL",
"text": [
"ASC"
],
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[
765,
768
]
],
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},
{
"id": "17258485_T24",
"type": "CHEMICAL",
"text": [
"Na(+)"
],
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[
800,
805
]
],
"normalized": []
},
{
"id": "17258485_T25",
"type": "CHEMICAL",
"text": [
"4,4'-diisothiocyanostilbene-2,2'-disulfonic acid"
],
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[
1035,
1083
]
],
"normalized": []
},
{
"id": "17258485_T26",
"type": "CHEMICAL",
"text": [
"DIDS"
],
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[
1085,
1089
]
],
"normalized": []
},
{
"id": "17258485_T27",
"type": "CHEMICAL",
"text": [
"5-ethylisopropylamiloride"
],
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[
1095,
1120
]
],
"normalized": []
},
{
"id": "17258485_T28",
"type": "CHEMICAL",
"text": [
"Vitamin C"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "17258485_T29",
"type": "GENE-N",
"text": [
"anion exchangers"
],
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[
1141,
1157
]
],
"normalized": []
},
{
"id": "17258485_T30",
"type": "GENE-N",
"text": [
"sodium-proton exchangers"
],
"offsets": [
[
1162,
1186
]
],
"normalized": []
},
{
"id": "17258485_T31",
"type": "GENE-N",
"text": [
"chloride channel"
],
"offsets": [
[
1243,
1259
]
],
"normalized": []
},
{
"id": "17258485_T32",
"type": "GENE-N",
"text": [
"protein kinase C"
],
"offsets": [
[
1389,
1405
]
],
"normalized": []
},
{
"id": "17258485_T33",
"type": "GENE-N",
"text": [
"human vitamin C transporter"
],
"offsets": [
[
1509,
1536
]
],
"normalized": []
},
{
"id": "17258485_T34",
"type": "GENE-Y",
"text": [
"SVCT1"
],
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[
1537,
1542
]
],
"normalized": []
},
{
"id": "17258485_T35",
"type": "GENE-Y",
"text": [
"SLC23A1"
],
"offsets": [
[
1544,
1551
]
],
"normalized": []
},
{
"id": "17258485_T36",
"type": "GENE-Y",
"text": [
"chicken SVCT1"
],
"offsets": [
[
1669,
1682
]
],
"normalized": []
},
{
"id": "17258485_T37",
"type": "GENE-N",
"text": [
"vitamin C transporter"
],
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[
1827,
1848
]
],
"normalized": []
},
{
"id": "17258485_T38",
"type": "GENE-Y",
"text": [
"SVCT1"
],
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[
1850,
1855
]
],
"normalized": []
},
{
"id": "17258485_T39",
"type": "GENE-Y",
"text": [
"SVCT1"
],
"offsets": [
[
24,
29
]
],
"normalized": []
}
] | [] | [] | [
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"arg2_id": "17258485_T32",
"normalized": []
}
] |
23545568 | 23545568 | [
{
"id": "23545568_title",
"type": "title",
"text": [
"Stable and high-rate overcharge protection for rechargeable lithium batteries."
],
"offsets": [
[
0,
78
]
]
},
{
"id": "23545568_abstract",
"type": "abstract",
"text": [
"Rechargeable lithium or lithium-ion cells can be overcharge-protected by an electroactive polymer composite separator. The use of non-woven fibrous membranes instead of conventional microporous membranes as the composite substrates allowed better distribution of the electroactive polymer, which led to improved utilization and a 40-fold increase in sustainable current density. For the first time, stable overcharge protection for hundreds of cycles was demonstrated in several cell chemistries, including LiNi1/3Co1/3Mn1/3O2, LiFePO4, and spinel Li1.05Mn1.95O4 half-cells. Protection at a charging rate as high as 5 C was achieved at a steady state cell potential below 4.85 V."
],
"offsets": [
[
79,
758
]
]
}
] | [
{
"id": "23545568_T1",
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],
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92,
99
]
],
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},
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"id": "23545568_T2",
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],
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[
103,
110
]
],
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},
{
"id": "23545568_T3",
"type": "CHEMICAL",
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"LiNi1"
],
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[
586,
591
]
],
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},
{
"id": "23545568_T4",
"type": "CHEMICAL",
"text": [
"3Co1"
],
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[
592,
596
]
],
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},
{
"id": "23545568_T5",
"type": "CHEMICAL",
"text": [
"3Mn1"
],
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597,
601
]
],
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},
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"id": "23545568_T6",
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"3O2"
],
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602,
605
]
],
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"id": "23545568_T7",
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],
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607,
614
]
],
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],
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627,
641
]
],
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},
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"id": "23545568_T9",
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"text": [
"lithium"
],
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[
60,
67
]
],
"normalized": []
}
] | [] | [] | [] |
23152189 | 23152189 | [
{
"id": "23152189_title",
"type": "title",
"text": [
"2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation."
],
"offsets": [
[
0,
180
]
]
},
{
"id": "23152189_abstract",
"type": "abstract",
"text": [
"Chloracne is commonly observed in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); yet, the mechanism of toxicity is not well understood. Using normal human epidermal keratinocytes, we investigated the mechanism of TCDD-mediated enhancement of epidermal differentiation by integrating functional genomic, metabolomic, and biochemical analyses. TCDD increased the expression of 40% of the genes of the epidermal differentiation complex found on chromosome 1q21 and 75% of the genes required for de novo ceramide biosynthesis. Lipid analysis demonstrated that eight of the nine classes of ceramides were increased by TCDD, altering the ratio of ceramides to free fatty acids. TCDD decreased the expression of the glucose transporter, SLC2A1, and most of the glycolytic transcripts, followed by decreases in glycolytic intermediates, including pyruvate. NADH and Krebs cycle intermediates were decreased, whereas NAD(+) was increased. Mitochondrial glutathione (GSH) reductase activity and the GSH/glutathione disulfide ratio were decreased by TCDD, ultimately leading to mitochondrial dysfunction, characterized by decreased inner mitochondrial membrane potential and ATP production, and increased production of the reactive oxygen species (ROS), hydrogen peroxide. Aryl hydrocarbon receptor (AHR) antagonists blocked the response of many transcripts to TCDD, and the endpoints of decreased ATP production and differentiation, suggesting regulation by the AHR. Cotreatment of cells with chemical antioxidants or the enzyme catalase blocked the TCDD-mediated acceleration of keratinocyte cornified envelope formation, an endpoint of terminal differentiation. Thus, TCDD-mediated ROS production is a critical step in the mechanism of this chemical to accelerate keratinocyte differentiation."
],
"offsets": [
[
181,
1981
]
]
}
] | [
{
"id": "23152189_T1",
"type": "CHEMICAL",
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"GSH"
],
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[
1185,
1188
]
],
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},
{
"id": "23152189_T2",
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"text": [
"glutathione disulfide"
],
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[
1189,
1210
]
],
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},
{
"id": "23152189_T3",
"type": "CHEMICAL",
"text": [
"TCDD"
],
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[
1235,
1239
]
],
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},
{
"id": "23152189_T4",
"type": "CHEMICAL",
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"ATP"
],
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1360,
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]
],
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},
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"id": "23152189_T5",
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"oxygen"
],
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1417,
1423
]
],
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},
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"id": "23152189_T6",
"type": "CHEMICAL",
"text": [
"hydrogen peroxide"
],
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[
1439,
1456
]
],
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},
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"id": "23152189_T7",
"type": "CHEMICAL",
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"Aryl hydrocarbon"
],
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[
1458,
1474
]
],
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},
{
"id": "23152189_T8",
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"TCDD"
],
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[
1546,
1550
]
],
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},
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"id": "23152189_T9",
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"ATP"
],
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[
1583,
1586
]
],
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},
{
"id": "23152189_T10",
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"text": [
"TCDD"
],
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[
1736,
1740
]
],
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},
{
"id": "23152189_T11",
"type": "CHEMICAL",
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"TCDD"
],
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[
1856,
1860
]
],
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},
{
"id": "23152189_T12",
"type": "CHEMICAL",
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"TCDD"
],
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[
409,
413
]
],
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},
{
"id": "23152189_T13",
"type": "CHEMICAL",
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"TCDD"
],
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[
538,
542
]
],
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},
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"id": "23152189_T14",
"type": "CHEMICAL",
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"ceramide"
],
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[
696,
704
]
],
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},
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"id": "23152189_T15",
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"2,3,7,8-tetrachlorodibenzo-p-dioxin"
],
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[
233,
268
]
],
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},
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"id": "23152189_T16",
"type": "CHEMICAL",
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"ceramides"
],
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[
781,
790
]
],
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},
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"id": "23152189_T17",
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"text": [
"TCDD"
],
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[
809,
813
]
],
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},
{
"id": "23152189_T18",
"type": "CHEMICAL",
"text": [
"ceramides"
],
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[
837,
846
]
],
"normalized": []
},
{
"id": "23152189_T19",
"type": "CHEMICAL",
"text": [
"fatty acids"
],
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[
855,
866
]
],
"normalized": []
},
{
"id": "23152189_T20",
"type": "CHEMICAL",
"text": [
"TCDD"
],
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[
868,
872
]
],
"normalized": []
},
{
"id": "23152189_T21",
"type": "CHEMICAL",
"text": [
"glucose"
],
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[
905,
912
]
],
"normalized": []
},
{
"id": "23152189_T22",
"type": "CHEMICAL",
"text": [
"pyruvate"
],
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[
1035,
1043
]
],
"normalized": []
},
{
"id": "23152189_T23",
"type": "CHEMICAL",
"text": [
"NADH"
],
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[
1045,
1049
]
],
"normalized": []
},
{
"id": "23152189_T24",
"type": "CHEMICAL",
"text": [
"TCDD"
],
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[
270,
274
]
],
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},
{
"id": "23152189_T25",
"type": "CHEMICAL",
"text": [
"NAD(+)"
],
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[
1104,
1110
]
],
"normalized": []
},
{
"id": "23152189_T26",
"type": "CHEMICAL",
"text": [
"glutathione"
],
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[
1140,
1151
]
],
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},
{
"id": "23152189_T27",
"type": "CHEMICAL",
"text": [
"GSH"
],
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[
1153,
1156
]
],
"normalized": []
},
{
"id": "23152189_T28",
"type": "CHEMICAL",
"text": [
"2,3,7,8-Tetrachlorodibenzo-p-dioxin"
],
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[
0,
35
]
],
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},
{
"id": "23152189_T29",
"type": "CHEMICAL",
"text": [
"oxygen"
],
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[
68,
74
]
],
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},
{
"id": "23152189_T30",
"type": "GENE-Y",
"text": [
"Aryl hydrocarbon receptor"
],
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[
1458,
1483
]
],
"normalized": []
},
{
"id": "23152189_T31",
"type": "GENE-Y",
"text": [
"AHR"
],
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[
1485,
1488
]
],
"normalized": []
},
{
"id": "23152189_T32",
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"glucose transporter"
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"id": "23152189_T35",
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"SLC2A1"
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"glutathione (GSH) reductase"
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1140,
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]
],
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}
] | [] | [] | [
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"id": "23152189_0",
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"arg1_id": "23152189_T20",
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"normalized": []
},
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"id": "23152189_1",
"type": "INDIRECT-DOWNREGULATOR",
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{
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"type": "INHIBITOR",
"arg1_id": "23152189_T3",
"arg2_id": "23152189_T36",
"normalized": []
}
] |
7981624 | 7981624 | [
{
"id": "7981624_title",
"type": "title",
"text": [
"Annexin 1 regulation in human epidermal cells."
],
"offsets": [
[
0,
46
]
]
},
{
"id": "7981624_abstract",
"type": "abstract",
"text": [
"Annexin 1 (named p35, lipocortin I or calpactin II), initially described as a glucocorticoid induced protein, belongs to a new characterized family of intracellular proteins. In the skin, the role of annexins has still not been elucidated. In a previous study, we reported the localization of annexin 1 in both freshly isolated human epidermal cells and in cultured keratinocytes using immunofluorescence, FACS analysis and immunoblotting techniques. The protein was characterized by Western blot and immunoprecipitation as a 35 kDa protein. Results from in vivo studies confirmed the presence of annexin 1 in basal and suprabasal layers of normal human skin with modified reactivity patterns in hyperproliferative lesions. In the present study, the role of glucocorticoids in annexin 1 regulation was investigated in epidermal cells by Western blot and immunoprecipation assays. In contrast to other studies, we found that glucocorticoid treatment of epidermal cells led to a decrease in annexin 1 content in the cytoplasm and the membranes of cells. As annexin 1 was not detected in the nucleus of cells, we conclude that there was a down regulation of annexin 1 after glucocorticoid treatments rather than a translocation of the protein to the nucleus. Despite the absence of the signal peptide sequence necessary for protein secretion, annexin 1 was released in the keratinocyte culture medium. We found that the protein was secreted only in low Ca2+ medium (0.15 mM), this process required an active metabolism."
],
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47,
1563
]
]
}
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1497,
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47,
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"Annexin 1"
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0,
9
]
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}
] | [] | [] | [] |
11607047 | 11607047 | [
{
"id": "11607047_title",
"type": "title",
"text": [
"A review of the pharmacological and clinical profile of mirtazapine."
],
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0,
68
]
]
},
{
"id": "11607047_abstract",
"type": "abstract",
"text": [
"The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use."
],
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69,
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}
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382,
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"id": "11607047_T14",
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"mirtazapine"
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846,
857
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"id": "11607047_T15",
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"serotonin"
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1051,
1060
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56,
67
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"adrenergic alpha2-autoreceptors"
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234,
265
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270,
292
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316,
321
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326,
331
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"5-HT1A"
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401,
407
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631,
637
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639,
645
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"CYP3A4"
],
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651,
657
]
],
"normalized": []
}
] | [] | [] | [] |
12512695 | 12512695 | [
{
"id": "12512695_title",
"type": "title",
"text": [
"Vascular effects of COX inhibition and AT1 receptor blockade in transgenic rats harboring mouse renin-2 gene."
],
"offsets": [
[
0,
109
]
]
},
{
"id": "12512695_abstract",
"type": "abstract",
"text": [
"Ang II-induced endothelial dysfunction is associated with perivascular inflammation and increased superoxide production in the vascular wall. The present study examined the role of cyclo-oxygenase (COX)-synthetized eicosanoids in the pathogenesis of Ang II-induced endothelial dysfunction in transgenic rats harboring mouse renin-2 gene (mREN2 rats). Five-to-six-week-old, heterozygous mREN2 rats received the following drug regimens for 8 weeks: 1) vehicle, 2) cyclo-oxygenase-2 (COX-2) inhibitor (MF-tricyclic [3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)-2(5H)-furanone], 14 mg/kg p.o.), 3) COX-1/COX-2 inhibitor (sulindac, 14 mg/kg p.o.), 4) angiotensin II receptor antagonist (losartan 40 mg/kg p.o.). Normotensive Sprague Dawley (SD) rats served as controls. In vitro vascular responses of the descending aorta and renal artery were studied using organ bath system. mREN2 rats developed pronounced hypertension which was associated with impaired endothelium-dependent and endothelium-independent vascular relaxations in the aorta. In contrast, the relaxation responses of the renal arteries remained largely unchanged in mREN2 rats. Urinary NO, excretion, a marker of total body NO generation, was also decreased in mREN2 rats. Neither non-selective COX inhibitor sulindac nor COX-2 selective MF-tricyclic were capable of preventing Ang II-induced hypertension or endothelial dysfunction in mREN2 rats, whereas ATi receptor antagonist losartan completely normalized blood pressure, vascular relaxation responses as well as urinary NOx excretion. Our findings indicate that NO synthesis and/or bioavailability as well as the sensitivity of arterial smooth muscle cells to NO are decreased in mREN2 rats. The present study also demonstrated that COX does not play a central role in the pathogenesis of Ang II-induced endothelial dysfunction in mREN2 rats."
],
"offsets": [
[
110,
1977
]
]
}
] | [
{
"id": "12512695_T1",
"type": "CHEMICAL",
"text": [
"Ang II"
],
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[
110,
116
]
],
"normalized": []
},
{
"id": "12512695_T2",
"type": "CHEMICAL",
"text": [
"NO"
],
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1265,
1267
]
],
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},
{
"id": "12512695_T3",
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"NO"
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1303,
1305
]
],
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},
{
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[
1388,
1396
]
],
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},
{
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1417,
1429
]
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1457,
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1559,
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]
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"Ang II"
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]
],
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"id": "12512695_T11",
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"text": [
"eicosanoids"
],
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325,
336
]
],
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"id": "12512695_T12",
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"Ang II"
],
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[
360,
366
]
],
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},
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"MF-tricyclic"
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609,
621
]
],
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},
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"3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)-2(5H)-furanone"
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]
],
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},
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"id": "12512695_T15",
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"sulindac"
],
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[
735,
743
]
],
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},
{
"id": "12512695_T16",
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"text": [
"angiotensin II"
],
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[
764,
778
]
],
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},
{
"id": "12512695_T17",
"type": "CHEMICAL",
"text": [
"superoxide"
],
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[
208,
218
]
],
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},
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"id": "12512695_T18",
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"text": [
"Ang II"
],
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110,
116
]
],
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},
{
"id": "12512695_T19",
"type": "GENE-Y",
"text": [
"mREN2"
],
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[
1245,
1250
]
],
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},
{
"id": "12512695_T20",
"type": "GENE-Y",
"text": [
"mREN2"
],
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[
1340,
1345
]
],
"normalized": []
},
{
"id": "12512695_T21",
"type": "GENE-N",
"text": [
"COX"
],
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[
1374,
1377
]
],
"normalized": []
},
{
"id": "12512695_T22",
"type": "GENE-Y",
"text": [
"COX-2"
],
"offsets": [
[
1401,
1406
]
],
"normalized": []
},
{
"id": "12512695_T23",
"type": "GENE-Y",
"text": [
"Ang II"
],
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[
1457,
1463
]
],
"normalized": []
},
{
"id": "12512695_T24",
"type": "GENE-Y",
"text": [
"mREN2"
],
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[
1515,
1520
]
],
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},
{
"id": "12512695_T25",
"type": "GENE-N",
"text": [
"ATi"
],
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[
1535,
1538
]
],
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},
{
"id": "12512695_T26",
"type": "GENE-Y",
"text": [
"mREN2"
],
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[
1815,
1820
]
],
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},
{
"id": "12512695_T27",
"type": "GENE-N",
"text": [
"COX"
],
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[
1868,
1871
]
],
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},
{
"id": "12512695_T28",
"type": "GENE-N",
"text": [
"cyclo-oxygenase"
],
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[
291,
306
]
],
"normalized": []
},
{
"id": "12512695_T29",
"type": "GENE-Y",
"text": [
"Ang II"
],
"offsets": [
[
1924,
1930
]
],
"normalized": []
},
{
"id": "12512695_T30",
"type": "GENE-Y",
"text": [
"mREN2"
],
"offsets": [
[
1966,
1971
]
],
"normalized": []
},
{
"id": "12512695_T31",
"type": "GENE-N",
"text": [
"COX"
],
"offsets": [
[
308,
311
]
],
"normalized": []
},
{
"id": "12512695_T32",
"type": "GENE-Y",
"text": [
"Ang II"
],
"offsets": [
[
360,
366
]
],
"normalized": []
},
{
"id": "12512695_T33",
"type": "GENE-Y",
"text": [
"mouse renin-2"
],
"offsets": [
[
428,
441
]
],
"normalized": []
},
{
"id": "12512695_T34",
"type": "GENE-Y",
"text": [
"mREN2"
],
"offsets": [
[
448,
453
]
],
"normalized": []
},
{
"id": "12512695_T35",
"type": "GENE-Y",
"text": [
"mREN2"
],
"offsets": [
[
496,
501
]
],
"normalized": []
},
{
"id": "12512695_T36",
"type": "GENE-Y",
"text": [
"cyclo-oxygenase-2"
],
"offsets": [
[
572,
589
]
],
"normalized": []
},
{
"id": "12512695_T37",
"type": "GENE-Y",
"text": [
"COX-2"
],
"offsets": [
[
591,
596
]
],
"normalized": []
},
{
"id": "12512695_T38",
"type": "GENE-Y",
"text": [
"COX-1"
],
"offsets": [
[
712,
717
]
],
"normalized": []
},
{
"id": "12512695_T39",
"type": "GENE-Y",
"text": [
"COX-2"
],
"offsets": [
[
718,
723
]
],
"normalized": []
},
{
"id": "12512695_T40",
"type": "GENE-N",
"text": [
"angiotensin II receptor"
],
"offsets": [
[
764,
787
]
],
"normalized": []
},
{
"id": "12512695_T41",
"type": "GENE-Y",
"text": [
"mREN2"
],
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[
990,
995
]
],
"normalized": []
},
{
"id": "12512695_T42",
"type": "GENE-N",
"text": [
"COX"
],
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[
20,
23
]
],
"normalized": []
},
{
"id": "12512695_T43",
"type": "GENE-N",
"text": [
"AT1"
],
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[
39,
42
]
],
"normalized": []
},
{
"id": "12512695_T44",
"type": "GENE-Y",
"text": [
"mouse renin-2"
],
"offsets": [
[
90,
103
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "12512695_0",
"type": "PRODUCT-OF",
"arg1_id": "12512695_T11",
"arg2_id": "12512695_T28",
"normalized": []
},
{
"id": "12512695_1",
"type": "PRODUCT-OF",
"arg1_id": "12512695_T11",
"arg2_id": "12512695_T31",
"normalized": []
}
] |
23237733 | 23237733 | [
{
"id": "23237733_title",
"type": "title",
"text": [
"Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation."
],
"offsets": [
[
0,
165
]
]
},
{
"id": "23237733_abstract",
"type": "abstract",
"text": [
"Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT). Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions. The results showed that 100μM of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95.2%, 76.1%, 78.9%, 87.2%, 67.2%, 94.8%, and 91.7%, respectively. The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K(i)) to be 0.7μM, 0.3μM, and 18.3μM for UGT1A1, UGT1A9, and UGT1A10, respectively. All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms."
],
"offsets": [
[
166,
1518
]
]
}
] | [
{
"id": "23237733_T1",
"type": "CHEMICAL",
"text": [
"Isoliquiritigenin"
],
"offsets": [
[
166,
183
]
],
"normalized": []
},
{
"id": "23237733_T2",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
"offsets": [
[
1369,
1386
]
],
"normalized": []
},
{
"id": "23237733_T3",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
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[
1473,
1490
]
],
"normalized": []
},
{
"id": "23237733_T4",
"type": "CHEMICAL",
"text": [
"UDP"
],
"offsets": [
[
321,
324
]
],
"normalized": []
},
{
"id": "23237733_T5",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
"offsets": [
[
433,
450
]
],
"normalized": []
},
{
"id": "23237733_T6",
"type": "CHEMICAL",
"text": [
"4-methylumbelliferone"
],
"offsets": [
[
592,
613
]
],
"normalized": []
},
{
"id": "23237733_T7",
"type": "CHEMICAL",
"text": [
"chalcone"
],
"offsets": [
[
210,
218
]
],
"normalized": []
},
{
"id": "23237733_T8",
"type": "CHEMICAL",
"text": [
"4-MU"
],
"offsets": [
[
615,
619
]
],
"normalized": []
},
{
"id": "23237733_T9",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
"offsets": [
[
699,
716
]
],
"normalized": []
},
{
"id": "23237733_T10",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
"offsets": [
[
992,
1009
]
],
"normalized": []
},
{
"id": "23237733_T11",
"type": "CHEMICAL",
"text": [
"isoliquiritigenin"
],
"offsets": [
[
1132,
1149
]
],
"normalized": []
},
{
"id": "23237733_T12",
"type": "CHEMICAL",
"text": [
"Isoliquiritigenin"
],
"offsets": [
[
0,
17
]
],
"normalized": []
},
{
"id": "23237733_T13",
"type": "CHEMICAL",
"text": [
"4-methylumbelliferone"
],
"offsets": [
[
120,
141
]
],
"normalized": []
},
{
"id": "23237733_T14",
"type": "CHEMICAL",
"text": [
"4-MU"
],
"offsets": [
[
143,
147
]
],
"normalized": []
},
{
"id": "23237733_T15",
"type": "CHEMICAL",
"text": [
"UDP"
],
"offsets": [
[
68,
71
]
],
"normalized": []
},
{
"id": "23237733_T16",
"type": "GENE-Y",
"text": [
"UGT1A1"
],
"offsets": [
[
1262,
1268
]
],
"normalized": []
},
{
"id": "23237733_T17",
"type": "GENE-Y",
"text": [
"UGT1A9"
],
"offsets": [
[
1270,
1276
]
],
"normalized": []
},
{
"id": "23237733_T18",
"type": "GENE-Y",
"text": [
"UGT1A10"
],
"offsets": [
[
1282,
1289
]
],
"normalized": []
},
{
"id": "23237733_T19",
"type": "GENE-N",
"text": [
"UGT"
],
"offsets": [
[
1505,
1508
]
],
"normalized": []
},
{
"id": "23237733_T20",
"type": "GENE-N",
"text": [
"UDP-glucuronosyltransferase"
],
"offsets": [
[
321,
348
]
],
"normalized": []
},
{
"id": "23237733_T21",
"type": "GENE-N",
"text": [
"UGT"
],
"offsets": [
[
350,
353
]
],
"normalized": []
},
{
"id": "23237733_T22",
"type": "GENE-N",
"text": [
"UGT"
],
"offsets": [
[
469,
472
]
],
"normalized": []
},
{
"id": "23237733_T23",
"type": "GENE-N",
"text": [
"UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10"
],
"offsets": [
[
520,
560
]
],
"normalized": []
},
{
"id": "23237733_T24",
"type": "GENE-N",
"text": [
"UGT"
],
"offsets": [
[
578,
581
]
],
"normalized": []
},
{
"id": "23237733_T25",
"type": "GENE-Y",
"text": [
"UGT1A1"
],
"offsets": [
[
743,
749
]
],
"normalized": []
},
{
"id": "23237733_T26",
"type": "GENE-Y",
"text": [
"UGT1A3"
],
"offsets": [
[
751,
757
]
],
"normalized": []
},
{
"id": "23237733_T27",
"type": "GENE-Y",
"text": [
"UGT1A6"
],
"offsets": [
[
759,
765
]
],
"normalized": []
},
{
"id": "23237733_T28",
"type": "GENE-Y",
"text": [
"UGT1A7"
],
"offsets": [
[
767,
773
]
],
"normalized": []
},
{
"id": "23237733_T29",
"type": "GENE-Y",
"text": [
"UGT1A8"
],
"offsets": [
[
775,
781
]
],
"normalized": []
},
{
"id": "23237733_T30",
"type": "GENE-Y",
"text": [
"UGT1A9"
],
"offsets": [
[
783,
789
]
],
"normalized": []
},
{
"id": "23237733_T31",
"type": "GENE-Y",
"text": [
"UGT1A10"
],
"offsets": [
[
795,
802
]
],
"normalized": []
},
{
"id": "23237733_T32",
"type": "GENE-Y",
"text": [
"UGT1A1"
],
"offsets": [
[
962,
968
]
],
"normalized": []
},
{
"id": "23237733_T33",
"type": "GENE-Y",
"text": [
"UGT1A9"
],
"offsets": [
[
970,
976
]
],
"normalized": []
},
{
"id": "23237733_T34",
"type": "GENE-Y",
"text": [
"UGT1A10"
],
"offsets": [
[
981,
988
]
],
"normalized": []
},
{
"id": "23237733_T35",
"type": "GENE-N",
"text": [
"UDP-glucuronosyltransferase"
],
"offsets": [
[
68,
95
]
],
"normalized": []
},
{
"id": "23237733_T36",
"type": "GENE-N",
"text": [
"UGT"
],
"offsets": [
[
97,
100
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23237733_0",
"type": "INHIBITOR",
"arg1_id": "23237733_T12",
"arg2_id": "23237733_T35",
"normalized": []
},
{
"id": "23237733_1",
"type": "INHIBITOR",
"arg1_id": "23237733_T12",
"arg2_id": "23237733_T36",
"normalized": []
},
{
"id": "23237733_2",
"type": "SUBSTRATE",
"arg1_id": "23237733_T13",
"arg2_id": "23237733_T35",
"normalized": []
},
{
"id": "23237733_3",
"type": "SUBSTRATE",
"arg1_id": "23237733_T13",
"arg2_id": "23237733_T36",
"normalized": []
},
{
"id": "23237733_4",
"type": "SUBSTRATE",
"arg1_id": "23237733_T14",
"arg2_id": "23237733_T35",
"normalized": []
},
{
"id": "23237733_5",
"type": "SUBSTRATE",
"arg1_id": "23237733_T14",
"arg2_id": "23237733_T36",
"normalized": []
},
{
"id": "23237733_6",
"type": "INHIBITOR",
"arg1_id": "23237733_T1",
"arg2_id": "23237733_T20",
"normalized": []
},
{
"id": "23237733_7",
"type": "INHIBITOR",
"arg1_id": "23237733_T1",
"arg2_id": "23237733_T21",
"normalized": []
},
{
"id": "23237733_8",
"type": "INHIBITOR",
"arg1_id": "23237733_T7",
"arg2_id": "23237733_T20",
"normalized": []
},
{
"id": "23237733_9",
"type": "INHIBITOR",
"arg1_id": "23237733_T7",
"arg2_id": "23237733_T21",
"normalized": []
},
{
"id": "23237733_10",
"type": "SUBSTRATE",
"arg1_id": "23237733_T6",
"arg2_id": "23237733_T24",
"normalized": []
},
{
"id": "23237733_11",
"type": "SUBSTRATE",
"arg1_id": "23237733_T8",
"arg2_id": "23237733_T24",
"normalized": []
},
{
"id": "23237733_12",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T25",
"normalized": []
},
{
"id": "23237733_13",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T26",
"normalized": []
},
{
"id": "23237733_14",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T27",
"normalized": []
},
{
"id": "23237733_15",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T28",
"normalized": []
},
{
"id": "23237733_16",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T29",
"normalized": []
},
{
"id": "23237733_17",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T30",
"normalized": []
},
{
"id": "23237733_18",
"type": "INHIBITOR",
"arg1_id": "23237733_T9",
"arg2_id": "23237733_T31",
"normalized": []
},
{
"id": "23237733_19",
"type": "INHIBITOR",
"arg1_id": "23237733_T10",
"arg2_id": "23237733_T32",
"normalized": []
},
{
"id": "23237733_20",
"type": "INHIBITOR",
"arg1_id": "23237733_T10",
"arg2_id": "23237733_T33",
"normalized": []
},
{
"id": "23237733_21",
"type": "INHIBITOR",
"arg1_id": "23237733_T10",
"arg2_id": "23237733_T34",
"normalized": []
},
{
"id": "23237733_22",
"type": "INHIBITOR",
"arg1_id": "23237733_T11",
"arg2_id": "23237733_T16",
"normalized": []
},
{
"id": "23237733_23",
"type": "INHIBITOR",
"arg1_id": "23237733_T11",
"arg2_id": "23237733_T17",
"normalized": []
},
{
"id": "23237733_24",
"type": "INHIBITOR",
"arg1_id": "23237733_T11",
"arg2_id": "23237733_T18",
"normalized": []
},
{
"id": "23237733_25",
"type": "INHIBITOR",
"arg1_id": "23237733_T3",
"arg2_id": "23237733_T19",
"normalized": []
}
] |
23361305 | 23361305 | [
{
"id": "23361305_title",
"type": "title",
"text": [
"Left ventricular noncompaction (LVNC) and low mitochondrial membrane potential are specific for Barth syndrome."
],
"offsets": [
[
0,
111
]
]
},
{
"id": "23361305_abstract",
"type": "abstract",
"text": [
"Barth syndrome (BTHS) is an X-linked mitochondrial defect characterised by dilated cardiomyopathy, neutropaenia and 3-methylglutaconic aciduria (3-MGCA). We report on two affected brothers with c.646G > A (p.G216R) TAZ gene mutations. The pathogenicity of the mutation, as indicated by the structure-based functional analyses, was further confirmed by abnormal monolysocardiolipin/cardiolipin ratio in dry blood spots of the patients as well as the occurrence of this mutation in another reported BTHS proband. In both brothers, 2D-echocardiography revealed some features of left ventricular noncompaction (LVNC) despite marked differences in the course of the disease; the eldest child presented with isolated cardiomyopathy from late infancy, whereas the youngest showed severe lactic acidosis without 3-MGCA during the neonatal period. An examination of the patients' fibroblast cultures revealed that extremely low mitochondrial membrane potentials (mtΔΨ about 50 % of the control value) dominated other unspecific mitochondrial changes detected (respiratory chain dysfunction, abnormal ROS production and depressed antioxidant defense). 1) Our studies confirm generalised mitochondrial dysfunction in the skeletal muscle and the fibroblasts of BTHS patients, especially a severe impairment in the mtΔΨ and the inhibition of complex V activity. It can be hypothesised that impaired mtΔΨ and mitochondrial ATP synthase activity may contribute to episodes of cardiac arrhythmia that occurred unexpectedly in BTHS patients. 2) Severe lactic acidosis without 3-methylglutaconic aciduria in male neonates as well as an asymptomatic mild left ventricular noncompaction may characterise the ranges of natural history of Barth syndrome."
],
"offsets": [
[
112,
1844
]
]
}
] | [
{
"id": "23361305_T1",
"type": "CHEMICAL",
"text": [
"ATP"
],
"offsets": [
[
1521,
1524
]
],
"normalized": []
},
{
"id": "23361305_T2",
"type": "CHEMICAL",
"text": [
"monolysocardiolipin"
],
"offsets": [
[
473,
492
]
],
"normalized": []
},
{
"id": "23361305_T3",
"type": "CHEMICAL",
"text": [
"cardiolipin"
],
"offsets": [
[
493,
504
]
],
"normalized": []
},
{
"id": "23361305_T4",
"type": "GENE-N",
"text": [
"mitochondrial ATP synthase"
],
"offsets": [
[
1507,
1533
]
],
"normalized": []
},
{
"id": "23361305_T5",
"type": "GENE-N",
"text": [
"646G > A"
],
"offsets": [
[
308,
316
]
],
"normalized": []
},
{
"id": "23361305_T6",
"type": "GENE-N",
"text": [
"G216R"
],
"offsets": [
[
320,
325
]
],
"normalized": []
},
{
"id": "23361305_T7",
"type": "GENE-Y",
"text": [
"TAZ"
],
"offsets": [
[
327,
330
]
],
"normalized": []
}
] | [] | [] | [] |
9353417 | 9353417 | [
{
"id": "9353417_title",
"type": "title",
"text": [
"Differential regulation of D2 and D4 dopamine receptor mRNAs in the primate cerebral cortex vs. neostriatum: effects of chronic treatment with typical and atypical antipsychotic drugs."
],
"offsets": [
[
0,
184
]
]
},
{
"id": "9353417_abstract",
"type": "abstract",
"text": [
"The RNase Protection Assay was used to examine the regulation of D2 and D4 dopamine receptor mRNAs in the cerebral cortex and neostriatum of nonhuman primates after chronic treatment with a wide spectrum of antipsychotic medications (chlorpromazine, clozapine, haloperidol, molindone, olanzapine, pimozide, remoxipride and risperidone). Tiapride, a D2 antagonist that lacks antipsychotic activity, was also included. All drugs were administered orally for 6 months at doses recommended for humans. All antipsychotic drug treatments examined in this study caused a statistically significant up-regulation of both the long and short isoforms of the D2 receptor mRNAs in the prefrontal and temporal cortex. Tiapride, in contrast, significantly up-regulated only the level of D2-long mRNA in these areas. The same drug treatments produced less uniform effects in the neostriatum than in the cortex: clozapine and olanzapine failed to significantly elevate either D2-long or D2-short receptor messages in this structure unlike all other drugs, including tiapride. In both the cerebral cortex and striatum, D4 receptor mRNA was upregulated by certain typical (chlorpromazine and haloperidol) and certain atypical (clozapine, olanzapine and risperidone) antipsychotic agents as well as by tiapride. Other drugs of the typical (molindone and pimozide) and atypical (remoxipride) classes had no effect on D4 mRNA levels in either cortical or striatal tissue. The finding that up-regulation of D2 dopamine receptor mRNAs was a consistently observed effect of a wide range of antipsychotic agents in the cerebral cortex but not in the neostriatum, coupled with the fact that the D2-short isoforms in the cortex were not regulated by a nonantipsychotic D2 antagonist, tiapride, draws attention to the importance of the D2 dopamine receptor in the cerebral cortex as a potentially critical, common site of action of antipsychotic medications."
],
"offsets": [
[
185,
2114
]
]
}
] | [
{
"id": "9353417_T1",
"type": "CHEMICAL",
"text": [
"tiapride"
],
"offsets": [
[
1234,
1242
]
],
"normalized": []
},
{
"id": "9353417_T2",
"type": "CHEMICAL",
"text": [
"chlorpromazine"
],
"offsets": [
[
1339,
1353
]
],
"normalized": []
},
{
"id": "9353417_T3",
"type": "CHEMICAL",
"text": [
"haloperidol"
],
"offsets": [
[
1358,
1369
]
],
"normalized": []
},
{
"id": "9353417_T4",
"type": "CHEMICAL",
"text": [
"clozapine"
],
"offsets": [
[
1393,
1402
]
],
"normalized": []
},
{
"id": "9353417_T5",
"type": "CHEMICAL",
"text": [
"olanzapine"
],
"offsets": [
[
1404,
1414
]
],
"normalized": []
},
{
"id": "9353417_T6",
"type": "CHEMICAL",
"text": [
"risperidone"
],
"offsets": [
[
1419,
1430
]
],
"normalized": []
},
{
"id": "9353417_T7",
"type": "CHEMICAL",
"text": [
"tiapride"
],
"offsets": [
[
1467,
1475
]
],
"normalized": []
},
{
"id": "9353417_T8",
"type": "CHEMICAL",
"text": [
"molindone"
],
"offsets": [
[
1505,
1514
]
],
"normalized": []
},
{
"id": "9353417_T9",
"type": "CHEMICAL",
"text": [
"pimozide"
],
"offsets": [
[
1519,
1527
]
],
"normalized": []
},
{
"id": "9353417_T10",
"type": "CHEMICAL",
"text": [
"remoxipride"
],
"offsets": [
[
1543,
1554
]
],
"normalized": []
},
{
"id": "9353417_T11",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
1672,
1680
]
],
"normalized": []
},
{
"id": "9353417_T12",
"type": "CHEMICAL",
"text": [
"tiapride"
],
"offsets": [
[
1941,
1949
]
],
"normalized": []
},
{
"id": "9353417_T13",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
1995,
2003
]
],
"normalized": []
},
{
"id": "9353417_T14",
"type": "CHEMICAL",
"text": [
"chlorpromazine"
],
"offsets": [
[
419,
433
]
],
"normalized": []
},
{
"id": "9353417_T15",
"type": "CHEMICAL",
"text": [
"clozapine"
],
"offsets": [
[
435,
444
]
],
"normalized": []
},
{
"id": "9353417_T16",
"type": "CHEMICAL",
"text": [
"haloperidol"
],
"offsets": [
[
446,
457
]
],
"normalized": []
},
{
"id": "9353417_T17",
"type": "CHEMICAL",
"text": [
"molindone"
],
"offsets": [
[
459,
468
]
],
"normalized": []
},
{
"id": "9353417_T18",
"type": "CHEMICAL",
"text": [
"olanzapine"
],
"offsets": [
[
470,
480
]
],
"normalized": []
},
{
"id": "9353417_T19",
"type": "CHEMICAL",
"text": [
"pimozide"
],
"offsets": [
[
482,
490
]
],
"normalized": []
},
{
"id": "9353417_T20",
"type": "CHEMICAL",
"text": [
"remoxipride"
],
"offsets": [
[
492,
503
]
],
"normalized": []
},
{
"id": "9353417_T21",
"type": "CHEMICAL",
"text": [
"risperidone"
],
"offsets": [
[
508,
519
]
],
"normalized": []
},
{
"id": "9353417_T22",
"type": "CHEMICAL",
"text": [
"Tiapride"
],
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[
522,
530
]
],
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},
{
"id": "9353417_T23",
"type": "CHEMICAL",
"text": [
"Tiapride"
],
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[
889,
897
]
],
"normalized": []
},
{
"id": "9353417_T24",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
260,
268
]
],
"normalized": []
},
{
"id": "9353417_T25",
"type": "CHEMICAL",
"text": [
"clozapine"
],
"offsets": [
[
1080,
1089
]
],
"normalized": []
},
{
"id": "9353417_T26",
"type": "CHEMICAL",
"text": [
"olanzapine"
],
"offsets": [
[
1094,
1104
]
],
"normalized": []
},
{
"id": "9353417_T27",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
37,
45
]
],
"normalized": []
},
{
"id": "9353417_T28",
"type": "GENE-Y",
"text": [
"D4 receptor"
],
"offsets": [
[
1286,
1297
]
],
"normalized": []
},
{
"id": "9353417_T29",
"type": "GENE-Y",
"text": [
"D4"
],
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[
1581,
1583
]
],
"normalized": []
},
{
"id": "9353417_T30",
"type": "GENE-Y",
"text": [
"D2 dopamine receptor"
],
"offsets": [
[
1669,
1689
]
],
"normalized": []
},
{
"id": "9353417_T31",
"type": "GENE-Y",
"text": [
"D2-short"
],
"offsets": [
[
1853,
1861
]
],
"normalized": []
},
{
"id": "9353417_T32",
"type": "GENE-Y",
"text": [
"D2"
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1926,
1928
]
],
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},
{
"id": "9353417_T33",
"type": "GENE-Y",
"text": [
"D2 dopamine receptor"
],
"offsets": [
[
1992,
2012
]
],
"normalized": []
},
{
"id": "9353417_T34",
"type": "GENE-Y",
"text": [
"D2"
],
"offsets": [
[
534,
536
]
],
"normalized": []
},
{
"id": "9353417_T35",
"type": "GENE-Y",
"text": [
"D2 receptor"
],
"offsets": [
[
832,
843
]
],
"normalized": []
},
{
"id": "9353417_T36",
"type": "GENE-N",
"text": [
"D2 and D4 dopamine receptor"
],
"offsets": [
[
250,
277
]
],
"normalized": []
},
{
"id": "9353417_T37",
"type": "GENE-Y",
"text": [
"D2-long"
],
"offsets": [
[
957,
964
]
],
"normalized": []
},
{
"id": "9353417_T38",
"type": "GENE-Y",
"text": [
"D2-long"
],
"offsets": [
[
1144,
1151
]
],
"normalized": []
},
{
"id": "9353417_T39",
"type": "GENE-Y",
"text": [
"D2-short"
],
"offsets": [
[
1155,
1163
]
],
"normalized": []
},
{
"id": "9353417_T40",
"type": "GENE-N",
"text": [
"D2 and D4 dopamine receptor"
],
"offsets": [
[
27,
54
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "9353417_0",
"type": "ANTAGONIST",
"arg1_id": "9353417_T22",
"arg2_id": "9353417_T34",
"normalized": []
},
{
"id": "9353417_1",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T23",
"arg2_id": "9353417_T37",
"normalized": []
},
{
"id": "9353417_2",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T2",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_3",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T3",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_4",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T4",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_5",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T5",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_6",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T6",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_7",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "9353417_T7",
"arg2_id": "9353417_T28",
"normalized": []
},
{
"id": "9353417_8",
"type": "ANTAGONIST",
"arg1_id": "9353417_T12",
"arg2_id": "9353417_T32",
"normalized": []
}
] |
14585280 | 14585280 | [
{
"id": "14585280_title",
"type": "title",
"text": [
"Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS."
],
"offsets": [
[
0,
85
]
]
},
{
"id": "14585280_abstract",
"type": "abstract",
"text": [
"DNA methylation abnormalities have recently emerged as one of the most frequent molecular changes in hematopoietic neoplasms. Since methylation and transcriptional status are inversely correlated, the hypermethylation of genes involved in cell-cycle control and apoptosis could have a pathogenetic role in the development of cancer. In particular, high-risk myelodysplastic syndromes (MDS) and secondary leukemias show a high prevalence of tumor suppressor gene hypermethylation. The progression of chronic myeloproliferative diseases and of myelodysplastic syndromes, as well as that of lymphoproliferative diseases, is associated with an increased methylation rate, pointing to a role for hypermethylation of critical promoter regions in the transformation to more aggressive phenotypes. In the same line, a significantly worse prognosis has been shown for patients with hypermethylation of several genes compared to that of patients with unmethylated genes. For these reasons, the use of irreversible DNA methyltransferase inhibitors, such as 5-azacytidine and Decitabine, appears to be a promising option for the treatment of MDS and acute myeloid leukemia. In clinical trials, Azacytidine results in a significantly higher response rate, improved quality of life, reduced risk of leukemic transformation, and improved survival compared to supportive care. Similarly, Decitabine showed favorable results, promising response rates, a good nonhematologic toxicity profile, and a trend for better survival compared to intensive chemotherapy, particularly in older patients. The synergistic effect of histone deacetylase inhibitors, including phenylbutyrate (PB), in reactivating silenced genes encouraged clinical studies on the combination of PB and demethylating agents in hematological diseases, characterized by p15 silencing. The sequential administration of a \"first generation\" demethylating agent and HDAC inhibitors gave preliminary evidence of a reduced methylation of target genes, as also described with Decitabine. Clinical trials are still ongoing, and preliminary data indicate for the first time that the natural history of MDS may be changed by a non-intensive treatment, characterized by an outstanding toxicity profile."
],
"offsets": [
[
86,
2325
]
]
}
] | [
{
"id": "14585280_T1",
"type": "CHEMICAL",
"text": [
"5-azacytidine"
],
"offsets": [
[
1132,
1145
]
],
"normalized": []
},
{
"id": "14585280_T2",
"type": "CHEMICAL",
"text": [
"Decitabine"
],
"offsets": [
[
1150,
1160
]
],
"normalized": []
},
{
"id": "14585280_T3",
"type": "CHEMICAL",
"text": [
"Azacytidine"
],
"offsets": [
[
1268,
1279
]
],
"normalized": []
},
{
"id": "14585280_T4",
"type": "CHEMICAL",
"text": [
"Decitabine"
],
"offsets": [
[
1458,
1468
]
],
"normalized": []
},
{
"id": "14585280_T5",
"type": "CHEMICAL",
"text": [
"phenylbutyrate"
],
"offsets": [
[
1729,
1743
]
],
"normalized": []
},
{
"id": "14585280_T6",
"type": "CHEMICAL",
"text": [
"PB"
],
"offsets": [
[
1745,
1747
]
],
"normalized": []
},
{
"id": "14585280_T7",
"type": "CHEMICAL",
"text": [
"PB"
],
"offsets": [
[
1831,
1833
]
],
"normalized": []
},
{
"id": "14585280_T8",
"type": "CHEMICAL",
"text": [
"Decitabine"
],
"offsets": [
[
2103,
2113
]
],
"normalized": []
},
{
"id": "14585280_T9",
"type": "GENE-N",
"text": [
"DNA methyltransferase"
],
"offsets": [
[
1090,
1111
]
],
"normalized": []
},
{
"id": "14585280_T10",
"type": "GENE-N",
"text": [
"histone deacetylase"
],
"offsets": [
[
1687,
1706
]
],
"normalized": []
},
{
"id": "14585280_T11",
"type": "GENE-Y",
"text": [
"p15"
],
"offsets": [
[
1903,
1906
]
],
"normalized": []
},
{
"id": "14585280_T12",
"type": "GENE-N",
"text": [
"HDAC"
],
"offsets": [
[
1996,
2000
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "14585280_0",
"type": "INHIBITOR",
"arg1_id": "14585280_T1",
"arg2_id": "14585280_T9",
"normalized": []
},
{
"id": "14585280_1",
"type": "INHIBITOR",
"arg1_id": "14585280_T2",
"arg2_id": "14585280_T9",
"normalized": []
},
{
"id": "14585280_2",
"type": "INHIBITOR",
"arg1_id": "14585280_T5",
"arg2_id": "14585280_T10",
"normalized": []
},
{
"id": "14585280_3",
"type": "INHIBITOR",
"arg1_id": "14585280_T6",
"arg2_id": "14585280_T10",
"normalized": []
}
] |
23211364 | 23211364 | [
{
"id": "23211364_title",
"type": "title",
"text": [
"AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator."
],
"offsets": [
[
0,
77
]
]
},
{
"id": "23211364_abstract",
"type": "abstract",
"text": [
"Candesartan is an angiotensin II type 1 receptor blocker (ARB) that has been to shown to limit ischemic stroke and improve stroke outcome. In experimental stroke, candesartan induces a proangiogenic effect that is partly attributable to vascular endothelial growth factor. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has been reported to have angiogenic effects and play an important role in recovery after stroke. The purpose of this investigation was to determine the role of BDNF in the proangiogenic effect of candesartan in the brain under hypertensive conditions. Accordingly, spontaneously hypertensive rats were treated with candesartan, and brain tissue samples were collected for quantification of BDNF expression. In addition, human cerebromicrovascular endothelial cells were treated with either low-dose (1 ƒM) or high-dose (1 µM) angiotensin II alone or in combination with candesartan (0.16 µM) to assess the effect of candesartan treatment and BDNF involvement in the behavior of endothelial cells. Candesartan significantly increased the expression of BDNF in the SHR (P < 0.05). In addition, candesartan reversed the antiangiogenic effect of the 1-µM dose of AngII (P = 0.0001). The observed effects of candesartan were ablated by neutralizing the effects of BDNF. Treatment with the AT2 antagonist PD-123319 significantly reduced tube-like formation in endothelial cells. AT2 stimulation induced the BDNF expression and migration (P < 0.05). In conclusion, candesartan exerts a proangiogenic effect on brain microvascular endothelial cells treated with angiotensin II. This response is attributable to increased BDNF expression and is mediated through stimulation of the AT2 receptor."
],
"offsets": [
[
78,
1822
]
]
}
] | [
{
"id": "23211364_T1",
"type": "CHEMICAL",
"text": [
"Candesartan"
],
"offsets": [
[
78,
89
]
],
"normalized": []
},
{
"id": "23211364_T2",
"type": "CHEMICAL",
"text": [
"Candesartan"
],
"offsets": [
[
1134,
1145
]
],
"normalized": []
},
{
"id": "23211364_T3",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
1229,
1240
]
],
"normalized": []
},
{
"id": "23211364_T4",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
1340,
1351
]
],
"normalized": []
},
{
"id": "23211364_T5",
"type": "CHEMICAL",
"text": [
"PD-123319"
],
"offsets": [
[
1436,
1445
]
],
"normalized": []
},
{
"id": "23211364_T6",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
1595,
1606
]
],
"normalized": []
},
{
"id": "23211364_T7",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
241,
252
]
],
"normalized": []
},
{
"id": "23211364_T8",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
752,
763
]
],
"normalized": []
},
{
"id": "23211364_T9",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
1007,
1018
]
],
"normalized": []
},
{
"id": "23211364_T10",
"type": "CHEMICAL",
"text": [
"candesartan"
],
"offsets": [
[
1053,
1064
]
],
"normalized": []
},
{
"id": "23211364_T11",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
1079,
1083
]
],
"normalized": []
},
{
"id": "23211364_T12",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
1188,
1192
]
],
"normalized": []
},
{
"id": "23211364_T13",
"type": "GENE-Y",
"text": [
"AngII"
],
"offsets": [
[
1296,
1301
]
],
"normalized": []
},
{
"id": "23211364_T14",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
1396,
1400
]
],
"normalized": []
},
{
"id": "23211364_T15",
"type": "GENE-Y",
"text": [
"AT2"
],
"offsets": [
[
1421,
1424
]
],
"normalized": []
},
{
"id": "23211364_T16",
"type": "GENE-Y",
"text": [
"AT2"
],
"offsets": [
[
1510,
1513
]
],
"normalized": []
},
{
"id": "23211364_T17",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
1538,
1542
]
],
"normalized": []
},
{
"id": "23211364_T18",
"type": "GENE-Y",
"text": [
"angiotensin II"
],
"offsets": [
[
1691,
1705
]
],
"normalized": []
},
{
"id": "23211364_T19",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
1750,
1754
]
],
"normalized": []
},
{
"id": "23211364_T20",
"type": "GENE-Y",
"text": [
"AT2 receptor"
],
"offsets": [
[
1809,
1821
]
],
"normalized": []
},
{
"id": "23211364_T21",
"type": "GENE-Y",
"text": [
"angiotensin II type 1 receptor"
],
"offsets": [
[
96,
126
]
],
"normalized": []
},
{
"id": "23211364_T22",
"type": "GENE-Y",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
315,
349
]
],
"normalized": []
},
{
"id": "23211364_T23",
"type": "GENE-Y",
"text": [
"Brain-derived neurotrophic factor"
],
"offsets": [
[
351,
384
]
],
"normalized": []
},
{
"id": "23211364_T24",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
386,
390
]
],
"normalized": []
},
{
"id": "23211364_T25",
"type": "GENE-N",
"text": [
"neurotrophin"
],
"offsets": [
[
411,
423
]
],
"normalized": []
},
{
"id": "23211364_T26",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
597,
601
]
],
"normalized": []
},
{
"id": "23211364_T27",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
827,
831
]
],
"normalized": []
},
{
"id": "23211364_T28",
"type": "GENE-Y",
"text": [
"angiotensin II"
],
"offsets": [
[
963,
977
]
],
"normalized": []
},
{
"id": "23211364_T29",
"type": "GENE-Y",
"text": [
"AT1 receptor"
],
"offsets": [
[
0,
12
]
],
"normalized": []
},
{
"id": "23211364_T30",
"type": "GENE-Y",
"text": [
"BDNF"
],
"offsets": [
[
55,
59
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23211364_0",
"type": "INHIBITOR",
"arg1_id": "23211364_T1",
"arg2_id": "23211364_T21",
"normalized": []
},
{
"id": "23211364_1",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23211364_T2",
"arg2_id": "23211364_T12",
"normalized": []
},
{
"id": "23211364_2",
"type": "ANTAGONIST",
"arg1_id": "23211364_T5",
"arg2_id": "23211364_T15",
"normalized": []
}
] |
23624810 | 23624810 | [
{
"id": "23624810_title",
"type": "title",
"text": [
"Antiaggressive activity of central oxytocin in male rats."
],
"offsets": [
[
0,
57
]
]
},
{
"id": "23624810_abstract",
"type": "abstract",
"text": [
"RATIONALE: A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. OBJECTIVE: Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats. METHODS: Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder. RESULTS: Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals. CONCLUSIONS: These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction."
],
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35,
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"text": [
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],
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35,
43
]
],
"normalized": []
}
] | [] | [] | [] |
10626836 | 10626836 | [
{
"id": "10626836_title",
"type": "title",
"text": [
"Lithium modulates desensitization of the glutamate receptor subtype gluR3 in Xenopus oocytes."
],
"offsets": [
[
0,
93
]
]
},
{
"id": "10626836_abstract",
"type": "abstract",
"text": [
"Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the GluR3 flop splice variant and suggested that lithium might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). We now show that mutation of the 769R/ G desensitization site (Lomeli, H.M.J., Melcher, T., Hoger, T., Geiger, J.R., Kuner, T., Monyer, H., Higuchi, M.B.A. and Seeburg, P.H, Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science, 9(266) (1994) 1709-1713) greatly attenuates the lithium-induced potentiation of GluR3. Additionally, experiments with the non-desensitizing site-directed mutant GluR3(L507Y) (Stern-Bach, Y., Russo, S., Neuman, M. and Rosenmund, C., A point mutation in the glutamate binding site blocks desensitization of AMPA receptors. Neuron, 21 (1998) 907-918) further confirms that lithium enhances GluR3 responses by reducing desensitization, since lithium's effects are reversed in this mutant. Lithium's effects on GluR3 desensitization are distinct from the effects of aniracetam on desensitization. Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(L507Y) mutant, but has synergistic effects with lithium on wild-type receptors."
],
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94,
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]
]
}
] | [
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]
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]
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]
],
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]
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]
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155,
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]
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740,
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]
],
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},
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]
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]
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]
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1101,
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"GluR3"
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"L507Y"
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1504,
1509
]
],
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},
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"id": "10626836_T23",
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"GluR3 flop"
],
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264,
274
]
],
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},
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"type": "GENE-N",
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"glutamate receptor"
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464,
482
]
],
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},
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"AMPA receptor"
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155,
168
]
],
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"AMPA receptor"
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]
],
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"GluR3"
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169,
174
]
],
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]
],
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},
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"GluR3"
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]
],
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},
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"L507Y"
],
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]
],
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41,
59
]
],
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},
{
"id": "10626836_T32",
"type": "GENE-Y",
"text": [
"gluR3"
],
"offsets": [
[
68,
73
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "10626836_0",
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"arg2_id": "10626836_T23",
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},
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"id": "10626836_1",
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},
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{
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},
{
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"type": "ACTIVATOR",
"arg1_id": "10626836_T7",
"arg2_id": "10626836_T22",
"normalized": []
}
] |
23536522 | 23536522 | [
{
"id": "23536522_title",
"type": "title",
"text": [
"The effects of gender difference on monocrotaline-induced pulmonary hypertension in rats."
],
"offsets": [
[
0,
89
]
]
},
{
"id": "23536522_abstract",
"type": "abstract",
"text": [
"The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat. The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated. For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats. RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group. In the MCT group, RVP was significantly higher in males than females. MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats. In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats. The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females."
],
"offsets": [
[
90,
1691
]
]
}
] | [
{
"id": "23536522_T1",
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],
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[
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1175
]
],
"normalized": []
},
{
"id": "23536522_T2",
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],
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[
207,
220
]
],
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},
{
"id": "23536522_T3",
"type": "CHEMICAL",
"text": [
"MCT"
],
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[
222,
225
]
],
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},
{
"id": "23536522_T4",
"type": "CHEMICAL",
"text": [
"MCT"
],
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1446,
1449
]
],
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},
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"id": "23536522_T5",
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"MCT"
],
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1627,
1630
]
],
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},
{
"id": "23536522_T6",
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"MCT"
],
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379,
382
]
],
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},
{
"id": "23536522_T7",
"type": "CHEMICAL",
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"glutathione"
],
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[
602,
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]
],
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},
{
"id": "23536522_T8",
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"GSH"
],
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615,
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]
],
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},
{
"id": "23536522_T9",
"type": "CHEMICAL",
"text": [
"superoxide"
],
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630,
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]
],
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},
{
"id": "23536522_T10",
"type": "CHEMICAL",
"text": [
"glutathione"
],
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677,
688
]
],
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},
{
"id": "23536522_T11",
"type": "CHEMICAL",
"text": [
"S"
],
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[
689,
690
]
],
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},
{
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"MCT"
],
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845,
848
]
],
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},
{
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"MCT"
],
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893,
896
]
],
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},
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"MCT"
],
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956,
959
]
],
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},
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"GSH"
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1013,
1016
]
],
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},
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49
]
],
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},
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]
],
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},
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"SOD"
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]
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650
]
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},
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655
]
],
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},
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666
]
],
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},
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"CAT"
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668,
671
]
],
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},
{
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"glutathione-S-transferase"
],
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677,
702
]
],
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},
{
"id": "23536522_T24",
"type": "GENE-N",
"text": [
"GST"
],
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[
704,
707
]
],
"normalized": []
},
{
"id": "23536522_T25",
"type": "GENE-N",
"text": [
"GST"
],
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[
1034,
1037
]
],
"normalized": []
},
{
"id": "23536522_T26",
"type": "GENE-N",
"text": [
"SOD"
],
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[
1042,
1045
]
],
"normalized": []
},
{
"id": "23536522_T27",
"type": "GENE-Y",
"text": [
"CAT"
],
"offsets": [
[
1071,
1074
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23536522_0",
"type": "INHIBITOR",
"arg1_id": "23536522_T14",
"arg2_id": "23536522_T25",
"normalized": []
},
{
"id": "23536522_1",
"type": "INHIBITOR",
"arg1_id": "23536522_T14",
"arg2_id": "23536522_T26",
"normalized": []
},
{
"id": "23536522_2",
"type": "ACTIVATOR",
"arg1_id": "23536522_T14",
"arg2_id": "23536522_T27",
"normalized": []
}
] |
23198810 | 23198810 | [
{
"id": "23198810_title",
"type": "title",
"text": [
"Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1."
],
"offsets": [
[
0,
143
]
]
},
{
"id": "23198810_abstract",
"type": "abstract",
"text": [
"Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability."
],
"offsets": [
[
144,
1604
]
]
}
] | [
{
"id": "23198810_T1",
"type": "CHEMICAL",
"text": [
"quinone"
],
"offsets": [
[
1149,
1156
]
],
"normalized": []
},
{
"id": "23198810_T2",
"type": "CHEMICAL",
"text": [
"quinone"
],
"offsets": [
[
1206,
1213
]
],
"normalized": []
},
{
"id": "23198810_T3",
"type": "CHEMICAL",
"text": [
"naphthalimide"
],
"offsets": [
[
840,
853
]
],
"normalized": []
},
{
"id": "23198810_T4",
"type": "CHEMICAL",
"text": [
"quinone"
],
"offsets": [
[
894,
901
]
],
"normalized": []
},
{
"id": "23198810_T5",
"type": "CHEMICAL",
"text": [
"quinone"
],
"offsets": [
[
996,
1003
]
],
"normalized": []
},
{
"id": "23198810_T6",
"type": "GENE-Y",
"text": [
"human NAD(P)H:quinone oxidoreductase isozyme 1"
],
"offsets": [
[
1192,
1238
]
],
"normalized": []
},
{
"id": "23198810_T7",
"type": "GENE-Y",
"text": [
"hNQO1"
],
"offsets": [
[
1240,
1245
]
],
"normalized": []
},
{
"id": "23198810_T8",
"type": "GENE-Y",
"text": [
"NQO1"
],
"offsets": [
[
1307,
1311
]
],
"normalized": []
},
{
"id": "23198810_T9",
"type": "GENE-Y",
"text": [
"NQO1"
],
"offsets": [
[
138,
142
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23198810_0",
"type": "SUBSTRATE",
"arg1_id": "23198810_T1",
"arg2_id": "23198810_T6",
"normalized": []
},
{
"id": "23198810_1",
"type": "SUBSTRATE",
"arg1_id": "23198810_T1",
"arg2_id": "23198810_T7",
"normalized": []
}
] |
11426832 | 11426832 | [
{
"id": "11426832_title",
"type": "title",
"text": [
"Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters."
],
"offsets": [
[
0,
118
]
]
},
{
"id": "11426832_abstract",
"type": "abstract",
"text": [
"The organic anion transport system is involved in the tubular excretion of various clinically important drugs. The purpose of this study was to characterize the effects of various organic anion transport inhibitors on organic anion transport using proximal tubule cells stably expressing human organic anion transporter 1 (human-OAT1) and human-OAT3, which are localized to the basolateral membrane of the proximal tubule. Organic anion transport inhibitors including betamipron, cilastatin, KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) and probenecid significantly inhibited human-OAT1- and human-OAT3-mediated organic anion uptake in a dose-dependent manner. Kinetic analyses revealed that these inhibitions were competitive. The Ki values of betamipron, cilastatin, KW-3902 and probencid for human-OAT1 were 23.6, 1470, 7.82 and 12.1 microM, whereas those for human-OAT3 were 48.3, 231, 3.70 and 9.0 microM. These results suggest that betamipron and probenecid could inhibit both human-OAT1- and human-OAT3-mediated organic anion transport in vivo, whereas cilastatin could inhibit only human-OAT3-mediated one. In contrast, KW-3902 did not exert the effects of significance, whereas KW-3902 was the most potent."
],
"offsets": [
[
119,
1342
]
]
}
] | [
{
"id": "11426832_T1",
"type": "CHEMICAL",
"text": [
"cilastatin"
],
"offsets": [
[
1187,
1197
]
],
"normalized": []
},
{
"id": "11426832_T2",
"type": "CHEMICAL",
"text": [
"KW-3902"
],
"offsets": [
[
1255,
1262
]
],
"normalized": []
},
{
"id": "11426832_T3",
"type": "CHEMICAL",
"text": [
"KW-3902"
],
"offsets": [
[
1314,
1321
]
],
"normalized": []
},
{
"id": "11426832_T4",
"type": "CHEMICAL",
"text": [
"betamipron"
],
"offsets": [
[
587,
597
]
],
"normalized": []
},
{
"id": "11426832_T5",
"type": "CHEMICAL",
"text": [
"cilastatin"
],
"offsets": [
[
599,
609
]
],
"normalized": []
},
{
"id": "11426832_T6",
"type": "CHEMICAL",
"text": [
"KW-3902"
],
"offsets": [
[
611,
618
]
],
"normalized": []
},
{
"id": "11426832_T7",
"type": "CHEMICAL",
"text": [
"8-(noradamantan-3-yl)-1,3-dipropylxanthine"
],
"offsets": [
[
620,
662
]
],
"normalized": []
},
{
"id": "11426832_T8",
"type": "CHEMICAL",
"text": [
"betamipron"
],
"offsets": [
[
872,
882
]
],
"normalized": []
},
{
"id": "11426832_T9",
"type": "CHEMICAL",
"text": [
"cilastatin"
],
"offsets": [
[
884,
894
]
],
"normalized": []
},
{
"id": "11426832_T10",
"type": "CHEMICAL",
"text": [
"KW-3902"
],
"offsets": [
[
896,
903
]
],
"normalized": []
},
{
"id": "11426832_T11",
"type": "CHEMICAL",
"text": [
"probencid"
],
"offsets": [
[
908,
917
]
],
"normalized": []
},
{
"id": "11426832_T12",
"type": "CHEMICAL",
"text": [
"betamipron"
],
"offsets": [
[
1065,
1075
]
],
"normalized": []
},
{
"id": "11426832_T13",
"type": "CHEMICAL",
"text": [
"probenecid"
],
"offsets": [
[
1080,
1090
]
],
"normalized": []
},
{
"id": "11426832_T14",
"type": "GENE-Y",
"text": [
"human-OAT3"
],
"offsets": [
[
1126,
1136
]
],
"normalized": []
},
{
"id": "11426832_T15",
"type": "GENE-Y",
"text": [
"human-OAT3"
],
"offsets": [
[
1217,
1227
]
],
"normalized": []
},
{
"id": "11426832_T16",
"type": "GENE-Y",
"text": [
"human organic anion transporter 1"
],
"offsets": [
[
407,
440
]
],
"normalized": []
},
{
"id": "11426832_T17",
"type": "GENE-Y",
"text": [
"human-OAT1"
],
"offsets": [
[
442,
452
]
],
"normalized": []
},
{
"id": "11426832_T18",
"type": "GENE-Y",
"text": [
"human-OAT3"
],
"offsets": [
[
458,
468
]
],
"normalized": []
},
{
"id": "11426832_T19",
"type": "GENE-Y",
"text": [
"human-OAT1"
],
"offsets": [
[
703,
713
]
],
"normalized": []
},
{
"id": "11426832_T20",
"type": "GENE-Y",
"text": [
"human-OAT3"
],
"offsets": [
[
719,
729
]
],
"normalized": []
},
{
"id": "11426832_T21",
"type": "GENE-Y",
"text": [
"human-OAT1"
],
"offsets": [
[
922,
932
]
],
"normalized": []
},
{
"id": "11426832_T22",
"type": "GENE-Y",
"text": [
"human-OAT3"
],
"offsets": [
[
990,
1000
]
],
"normalized": []
},
{
"id": "11426832_T23",
"type": "GENE-Y",
"text": [
"human-OAT1"
],
"offsets": [
[
1110,
1120
]
],
"normalized": []
},
{
"id": "11426832_T24",
"type": "GENE-N",
"text": [
"human organic anion transporters"
],
"offsets": [
[
85,
117
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "11426832_0",
"type": "INHIBITOR",
"arg1_id": "11426832_T7",
"arg2_id": "11426832_T19",
"normalized": []
},
{
"id": "11426832_1",
"type": "INHIBITOR",
"arg1_id": "11426832_T4",
"arg2_id": "11426832_T19",
"normalized": []
},
{
"id": "11426832_2",
"type": "INHIBITOR",
"arg1_id": "11426832_T5",
"arg2_id": "11426832_T19",
"normalized": []
},
{
"id": "11426832_3",
"type": "INHIBITOR",
"arg1_id": "11426832_T6",
"arg2_id": "11426832_T19",
"normalized": []
},
{
"id": "11426832_4",
"type": "INHIBITOR",
"arg1_id": "11426832_T4",
"arg2_id": "11426832_T20",
"normalized": []
},
{
"id": "11426832_5",
"type": "INHIBITOR",
"arg1_id": "11426832_T5",
"arg2_id": "11426832_T20",
"normalized": []
},
{
"id": "11426832_6",
"type": "INHIBITOR",
"arg1_id": "11426832_T6",
"arg2_id": "11426832_T20",
"normalized": []
},
{
"id": "11426832_7",
"type": "INHIBITOR",
"arg1_id": "11426832_T8",
"arg2_id": "11426832_T21",
"normalized": []
},
{
"id": "11426832_8",
"type": "INHIBITOR",
"arg1_id": "11426832_T9",
"arg2_id": "11426832_T21",
"normalized": []
},
{
"id": "11426832_9",
"type": "INHIBITOR",
"arg1_id": "11426832_T10",
"arg2_id": "11426832_T21",
"normalized": []
},
{
"id": "11426832_10",
"type": "INHIBITOR",
"arg1_id": "11426832_T11",
"arg2_id": "11426832_T21",
"normalized": []
},
{
"id": "11426832_11",
"type": "INHIBITOR",
"arg1_id": "11426832_T8",
"arg2_id": "11426832_T22",
"normalized": []
},
{
"id": "11426832_12",
"type": "INHIBITOR",
"arg1_id": "11426832_T9",
"arg2_id": "11426832_T22",
"normalized": []
},
{
"id": "11426832_13",
"type": "INHIBITOR",
"arg1_id": "11426832_T10",
"arg2_id": "11426832_T22",
"normalized": []
},
{
"id": "11426832_14",
"type": "INHIBITOR",
"arg1_id": "11426832_T11",
"arg2_id": "11426832_T22",
"normalized": []
},
{
"id": "11426832_15",
"type": "INHIBITOR",
"arg1_id": "11426832_T12",
"arg2_id": "11426832_T23",
"normalized": []
},
{
"id": "11426832_16",
"type": "INHIBITOR",
"arg1_id": "11426832_T12",
"arg2_id": "11426832_T14",
"normalized": []
},
{
"id": "11426832_17",
"type": "INHIBITOR",
"arg1_id": "11426832_T1",
"arg2_id": "11426832_T15",
"normalized": []
}
] |
10047461 | 10047461 | [
{
"id": "10047461_title",
"type": "title",
"text": [
"Cyclin E-cdk2 activation is associated with cell cycle arrest and inhibition of DNA replication induced by the thymidylate synthase inhibitor Tomudex."
],
"offsets": [
[
0,
150
]
]
},
{
"id": "10047461_abstract",
"type": "abstract",
"text": [
"Tomudex (ZD1694) is a specific antifolate-based thymidylate synthase inhibitor active in a variety of solid tumor malignancies. Studies were carried out in vitro to evaluate downstream molecular alterations induced as a consequence of the potent and sustained inhibition of thymidylate synthase by Tomudex. Twenty-four hours following the initial 2-h treatment with Tomudex, human A253 head and neck squamous carcinoma cells, not expressing p53 and p21(WAF1), were accumulated with DNA content characteristic of early S phase of the cell cycle with a concomitant reduction of cells in G1 and G2/M phases. The changes in cyclin and cdk protein expression and their kinase activities were examined in control and drug-treated A253 cells. Tomudex treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and cdk2 protein expression and kinase activities 24 h after a 2-h exposure. Although cyclin A protein expression was markedly increased, cyclin A kinase activity was only slightly increased. Cyclin D1, cyclin B, cdk4, and cdc2 protein expression and kinase activities remain constant. Lack of activation of cyclin A- and B-cdc2 was associated with a reduced proportion of cells in G2/M phases. Increased cyclin E-cdk2 protein expression was accompanied by the inhibition of DNA synthesis, with a decrease in E2F-1 expression. These results propose that cyclin E-cdk2 kinase can negatively regulate DNA replication. The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by Tomudex indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance. Provision of dThyd more than 24 h after exposure to Tomudex allowed cells to replicate DNA for a single cycle back to G1, but did not prevent the profound growth-inhibitory effect manifested in the following 5 days. Tomudex treatment resulted in a time-dependent induction of the megabase DNA fragments, followed by secondary 50- to 300-kb DNA fragmentation. The 50- to 300-kb DNA fragmentation may be derived from the inhibition of DNA synthesis associated with cyclin E-cdk2 activation. These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by Tomudex and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 kinase activities. Activation of cyclin E and cdk2 kinases allows cells to transit from G1 to S phase accompanied by the inhibition of DNA synthesis. The changes in cell cycle regulatory proteins associated with growth inhibition and DNA damage by Tomudex are not p53 dependent."
],
"offsets": [
[
151,
2889
]
]
}
] | [
{
"id": "10047461_T1",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
151,
158
]
],
"normalized": []
},
{
"id": "10047461_T2",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
1697,
1704
]
],
"normalized": []
},
{
"id": "10047461_T3",
"type": "CHEMICAL",
"text": [
"thymidylate"
],
"offsets": [
[
1805,
1816
]
],
"normalized": []
},
{
"id": "10047461_T4",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
1913,
1920
]
],
"normalized": []
},
{
"id": "10047461_T5",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
2077,
2084
]
],
"normalized": []
},
{
"id": "10047461_T6",
"type": "CHEMICAL",
"text": [
"thymidylate"
],
"offsets": [
[
2453,
2464
]
],
"normalized": []
},
{
"id": "10047461_T7",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
2477,
2484
]
],
"normalized": []
},
{
"id": "10047461_T8",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
2859,
2866
]
],
"normalized": []
},
{
"id": "10047461_T9",
"type": "CHEMICAL",
"text": [
"thymidylate"
],
"offsets": [
[
425,
436
]
],
"normalized": []
},
{
"id": "10047461_T10",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
449,
456
]
],
"normalized": []
},
{
"id": "10047461_T11",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
517,
524
]
],
"normalized": []
},
{
"id": "10047461_T12",
"type": "CHEMICAL",
"text": [
"thymidylate"
],
"offsets": [
[
199,
210
]
],
"normalized": []
},
{
"id": "10047461_T13",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
887,
894
]
],
"normalized": []
},
{
"id": "10047461_T14",
"type": "CHEMICAL",
"text": [
"ZD1694"
],
"offsets": [
[
160,
166
]
],
"normalized": []
},
{
"id": "10047461_T15",
"type": "CHEMICAL",
"text": [
"thymidylate"
],
"offsets": [
[
111,
122
]
],
"normalized": []
},
{
"id": "10047461_T16",
"type": "CHEMICAL",
"text": [
"Tomudex"
],
"offsets": [
[
142,
149
]
],
"normalized": []
},
{
"id": "10047461_T17",
"type": "GENE-Y",
"text": [
"Cyclin D1"
],
"offsets": [
[
1176,
1185
]
],
"normalized": []
},
{
"id": "10047461_T18",
"type": "GENE-Y",
"text": [
"cyclin B"
],
"offsets": [
[
1187,
1195
]
],
"normalized": []
},
{
"id": "10047461_T19",
"type": "GENE-Y",
"text": [
"cdk4"
],
"offsets": [
[
1197,
1201
]
],
"normalized": []
},
{
"id": "10047461_T20",
"type": "GENE-Y",
"text": [
"cdc2"
],
"offsets": [
[
1207,
1211
]
],
"normalized": []
},
{
"id": "10047461_T21",
"type": "GENE-N",
"text": [
"kinase"
],
"offsets": [
[
1235,
1241
]
],
"normalized": []
},
{
"id": "10047461_T22",
"type": "GENE-N",
"text": [
"cyclin A- and B"
],
"offsets": [
[
1292,
1307
]
],
"normalized": []
},
{
"id": "10047461_T23",
"type": "GENE-Y",
"text": [
"cdc2"
],
"offsets": [
[
1308,
1312
]
],
"normalized": []
},
{
"id": "10047461_T24",
"type": "GENE-Y",
"text": [
"cyclin E"
],
"offsets": [
[
1389,
1397
]
],
"normalized": []
},
{
"id": "10047461_T25",
"type": "GENE-Y",
"text": [
"cdk2"
],
"offsets": [
[
1398,
1402
]
],
"normalized": []
},
{
"id": "10047461_T26",
"type": "GENE-Y",
"text": [
"E2F-1"
],
"offsets": [
[
1493,
1498
]
],
"normalized": []
},
{
"id": "10047461_T27",
"type": "GENE-Y",
"text": [
"cyclin E"
],
"offsets": [
[
1538,
1546
]
],
"normalized": []
},
{
"id": "10047461_T28",
"type": "GENE-Y",
"text": [
"cdk2"
],
"offsets": [
[
1547,
1551
]
],
"normalized": []
},
{
"id": "10047461_T29",
"type": "GENE-N",
"text": [
"kinase"
],
"offsets": [
[
1552,
1558
]
],
"normalized": []
},
{
"id": "10047461_T30",
"type": "GENE-Y",
"text": [
"cyclin E"
],
"offsets": [
[
1635,
1643
]
],
"normalized": []
},
{
"id": "10047461_T31",
"type": "GENE-Y",
"text": [
"cdk2"
],
"offsets": [
[
1644,
1648
]
],
"normalized": []
},
{
"id": "10047461_T32",
"type": "GENE-Y",
"text": [
"cyclin E"
],
"offsets": [
[
1729,
1737
]
],
"normalized": []
},
{
"id": "10047461_T33",
"type": "GENE-Y",
"text": [
"cdk2"
],
"offsets": [
[
1738,
1742
]
],
"normalized": []
},
{
"id": "10047461_T34",
"type": "GENE-Y",
"text": [
"thymidylate synthase"
],
"offsets": [
[
1805,
1825
]
],
"normalized": []
},
{
"id": "10047461_T35",
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425,
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592,
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600,
603
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604,
608
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"id": "10047461_T50",
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199,
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771,
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782,
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975,
983
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"id": "10047461_T56",
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988,
992
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"id": "10047461_T57",
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1016,
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1070,
1078
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1122,
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0,
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"id": "10047461_T62",
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111,
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"cdk2"
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9,
13
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],
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}
] | [] | [] | [
{
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},
{
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},
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},
{
"id": "10047461_3",
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},
{
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},
{
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},
{
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},
{
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},
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"normalized": []
},
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"normalized": []
},
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},
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"normalized": []
},
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"id": "10047461_16",
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},
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"id": "10047461_17",
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},
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"type": "ACTIVATOR",
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"arg2_id": "10047461_T41",
"normalized": []
}
] |
9950599 | 9950599 | [
{
"id": "9950599_title",
"type": "title",
"text": [
"Oxidative stress induces differential gene expression in a human lens epithelial cell line."
],
"offsets": [
[
0,
91
]
]
},
{
"id": "9950599_abstract",
"type": "abstract",
"text": [
"PURPOSE: To identify differentially expressed genes in a human lens epithelial cell line exposed to oxidative stress. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) differential display was used to evaluate differential gene expression in a human lens epithelial cell line (SRA 01-04) when cells were exposed for 3 hours to a single bolus of 200 microM hydrogen peroxide. Differentially expressed genes were identified through DNA sequencing and a nucleotide database search. Differential expression was confirmed by northern blot and RT-PCR analyses. RESULTS: Using 18 primer sets, 28 RT-PCR products were differentially expressed between control and hydrogen peroxide-treated cells. In stressed cells, mitochondrial transcripts nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4 and cytochrome b were downregulated 4-fold. Of the cytoplasmic mRNAs, glutamine cyclotransferase decreased 10-fold, whereas cytokine-inducible nuclear protein, alternative splicing factor 2, and beta-hydroxyisobutyryl-coenzyme A hydrolase increased 2-, 4-, and 10-fold, respectively. Analysis of mitochondrial transcripts in a 24-hour time course showed that NADH dehydrogenase subunit 4 mRNA decreased by 2-fold as early as 1 hour after oxidative stress, whereas the rate of decrease was slower for cytochrome b, cytochrome oxidase III, and 16S rRNA. CONCLUSIONS: Oxidative stress induced specific expressed gene changes in hydrogen peroxide-treated lens cells, including genes involved in cellular respiration and mRNA and peptide processing. These early changes may reflect pathways involved in the defense, pathology, or both of the lens epithelium, which is exposed to oxidative stress throughout life."
],
"offsets": [
[
92,
1813
]
]
}
] | [
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"id": "9950599_T1",
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"beta-hydroxyisobutyryl"
],
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1101,
1123
]
],
"normalized": []
},
{
"id": "9950599_T2",
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"text": [
"coenzyme A"
],
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[
1124,
1134
]
],
"normalized": []
},
{
"id": "9950599_T3",
"type": "CHEMICAL",
"text": [
"NADH"
],
"offsets": [
[
1265,
1269
]
],
"normalized": []
},
{
"id": "9950599_T4",
"type": "CHEMICAL",
"text": [
"hydrogen peroxide"
],
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1531,
1548
]
],
"normalized": []
},
{
"id": "9950599_T5",
"type": "CHEMICAL",
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"hydrogen peroxide"
],
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464,
481
]
],
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},
{
"id": "9950599_T6",
"type": "CHEMICAL",
"text": [
"hydrogen peroxide"
],
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[
763,
780
]
],
"normalized": []
},
{
"id": "9950599_T7",
"type": "CHEMICAL",
"text": [
"nicotinamide adenine dinucleotide"
],
"offsets": [
[
841,
874
]
],
"normalized": []
},
{
"id": "9950599_T8",
"type": "CHEMICAL",
"text": [
"NADH"
],
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[
876,
880
]
],
"normalized": []
},
{
"id": "9950599_T9",
"type": "CHEMICAL",
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"glutamine"
],
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976,
985
]
],
"normalized": []
},
{
"id": "9950599_T10",
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1101,
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]
],
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},
{
"id": "9950599_T11",
"type": "GENE-Y",
"text": [
"NADH dehydrogenase subunit 4"
],
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1265,
1293
]
],
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},
{
"id": "9950599_T12",
"type": "GENE-Y",
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"cytochrome b"
],
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1406,
1418
]
],
"normalized": []
},
{
"id": "9950599_T13",
"type": "GENE-Y",
"text": [
"cytochrome oxidase III"
],
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1420,
1442
]
],
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},
{
"id": "9950599_T14",
"type": "GENE-Y",
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"nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4"
],
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841,
905
]
],
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},
{
"id": "9950599_T15",
"type": "GENE-Y",
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"cytochrome b"
],
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910,
922
]
],
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},
{
"id": "9950599_T16",
"type": "GENE-Y",
"text": [
"glutamine cyclotransferase"
],
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976,
1002
]
],
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},
{
"id": "9950599_T17",
"type": "GENE-Y",
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"cytokine-inducible nuclear protein"
],
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1030,
1064
]
],
"normalized": []
},
{
"id": "9950599_T18",
"type": "GENE-Y",
"text": [
"alternative splicing factor 2"
],
"offsets": [
[
1066,
1095
]
],
"normalized": []
}
] | [] | [] | [] |
18480678 | 18480678 | [
{
"id": "18480678_title",
"type": "title",
"text": [
"Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?"
],
"offsets": [
[
0,
105
]
]
},
{
"id": "18480678_abstract",
"type": "abstract",
"text": [
"d,l-threo-methylphenidate (MPH) is an effective first-line treatment for the symptoms associated with attention-deficit/hyperactivity disorder. threo-methylphenidate inhibits the dopamine transporter and the norepinephrine transporter, resulting in elevations of these monoamines after impulse release. Although MPH has long been administered as a racemic mixture of the 2 enantiomers, d-MPH and l-MPH, converging lines of evidence drawn from investigations using in vitro systems, animal models, and humans indicate that it is predominantly, if not exclusively, d-MPH that mediates the pharmacological/therapeutic actions of MPH. In both rodent and primate animal models, the binding of radiolabeled d-MPH to dopamine transporter was found to be selective, saturable, and reversible, whereas binding of l-MPH was diffuse and nonspecific. The behavioral effects of the enantiomers of MPH have been tested in several animal models, and results indicate these observed behavioral changes are likewise mediated by d-MPH, whereas l-MPH has little or no effect.The contribution of the l-isomer to the overall pharmacological profile of the racemate remains unclear, owing to several studies suggesting that l-MPH may not be merely an inert isomeric ballast. For example, behavioral studies conducted in rats demonstrate an attenuation of the effect of d-MPH in animals pretreated with l-MPH, suggesting that l-MPH may interfere with the action of the active enantiomer. The importance of MPH chirality to central nervous system MPH receptor targeting has culminated in human imaging studies revealing that d-MPH binds specifically to striatal structures, whereas l-MPH binding is nonspecific. Taken together, data from in vitro, animal, and human studies support the premise that the d-enantiomer of MPH mediates the neurophysiological actions of MPH and therefore likely mediates its clinical efficacy."
],
"offsets": [
[
106,
2004
]
]
}
] | [
{
"id": "18480678_T1",
"type": "CHEMICAL",
"text": [
"d,l-threo-methylphenidate"
],
"offsets": [
[
106,
131
]
],
"normalized": []
},
{
"id": "18480678_T2",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
"offsets": [
[
1117,
1122
]
],
"normalized": []
},
{
"id": "18480678_T3",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
"offsets": [
[
1132,
1137
]
],
"normalized": []
},
{
"id": "18480678_T4",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
"offsets": [
[
1308,
1313
]
],
"normalized": []
},
{
"id": "18480678_T5",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
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[
1453,
1458
]
],
"normalized": []
},
{
"id": "18480678_T6",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
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[
1486,
1491
]
],
"normalized": []
},
{
"id": "18480678_T7",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
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[
1509,
1514
]
],
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},
{
"id": "18480678_T8",
"type": "CHEMICAL",
"text": [
"threo-methylphenidate"
],
"offsets": [
[
250,
271
]
],
"normalized": []
},
{
"id": "18480678_T9",
"type": "CHEMICAL",
"text": [
"MPH"
],
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[
1589,
1592
]
],
"normalized": []
},
{
"id": "18480678_T10",
"type": "CHEMICAL",
"text": [
"MPH"
],
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[
1629,
1632
]
],
"normalized": []
},
{
"id": "18480678_T11",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
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[
1707,
1712
]
],
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},
{
"id": "18480678_T12",
"type": "CHEMICAL",
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"l-MPH"
],
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[
1764,
1769
]
],
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},
{
"id": "18480678_T13",
"type": "CHEMICAL",
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"d-enantiomer of MPH"
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1885,
1904
]
],
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{
"id": "18480678_T14",
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"dopamine"
],
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[
285,
293
]
],
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{
"id": "18480678_T15",
"type": "CHEMICAL",
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"MPH"
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[
1948,
1951
]
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{
"id": "18480678_T16",
"type": "CHEMICAL",
"text": [
"norepinephrine"
],
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[
314,
328
]
],
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},
{
"id": "18480678_T17",
"type": "CHEMICAL",
"text": [
"monoamines"
],
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[
375,
385
]
],
"normalized": []
},
{
"id": "18480678_T18",
"type": "CHEMICAL",
"text": [
"MPH"
],
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[
133,
136
]
],
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},
{
"id": "18480678_T19",
"type": "CHEMICAL",
"text": [
"MPH"
],
"offsets": [
[
418,
421
]
],
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},
{
"id": "18480678_T20",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
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[
492,
497
]
],
"normalized": []
},
{
"id": "18480678_T21",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
"offsets": [
[
502,
507
]
],
"normalized": []
},
{
"id": "18480678_T22",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
"offsets": [
[
669,
674
]
],
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},
{
"id": "18480678_T23",
"type": "CHEMICAL",
"text": [
"MPH"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "18480678_T24",
"type": "CHEMICAL",
"text": [
"d-MPH"
],
"offsets": [
[
807,
812
]
],
"normalized": []
},
{
"id": "18480678_T25",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
816,
824
]
],
"normalized": []
},
{
"id": "18480678_T26",
"type": "CHEMICAL",
"text": [
"l-MPH"
],
"offsets": [
[
910,
915
]
],
"normalized": []
},
{
"id": "18480678_T27",
"type": "CHEMICAL",
"text": [
"MPH"
],
"offsets": [
[
990,
993
]
],
"normalized": []
},
{
"id": "18480678_T28",
"type": "CHEMICAL",
"text": [
"methylphenidate"
],
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[
54,
69
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"MPH receptor"
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1629,
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"id": "18480678_T30",
"type": "GENE-Y",
"text": [
"dopamine transporter"
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[
285,
305
]
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},
{
"id": "18480678_T31",
"type": "GENE-Y",
"text": [
"norepinephrine transporter"
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314,
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"type": "GENE-N",
"text": [
"dopamine transporter"
],
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816,
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] | [] | [] | [
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] |
8697470 | 8697470 | [
{
"id": "8697470_title",
"type": "title",
"text": [
"[Inactivated factor VII exercises a powerful antithrombotic activity in an experimental model of recurrent arterial thrombosis]."
],
"offsets": [
[
0,
128
]
]
},
{
"id": "8697470_abstract",
"type": "abstract",
"text": [
"The extrinsic coagulation pathway is activated when tissue factor (TF) is exposed as a consequence of arterial damage. TF binds to factor VII (FVII) or activated FVII (FVIIa), generating a complex that activates both FX and FIX, ultimately leading to thrombin formation. To determine whether inhibition of FVII binding to TF would result in antithrombotic effects, active site-blocked FVIIa (FVIIai) was used in a rabbit model of intravascular thrombus formation. In addition, to study the interaction between extrinsic coagulation pathway activation and platelet aggregation, in the same model of intravascular thrombus formation, recombinant human FVIIa was administered in antiplatelet-treated rabbits. Cyclic flow variations (CFVs), due to recurrent thrombus formation, were initiated by placing an external constrictor around the endothelially-injured rabbit carotid arteries (Folt's model). Carotid blood flow was measured continuously by a Doppler flow probe placed proximally to the constrictor. CFVs were induced in 29 New Zealand White rabbits. After CFVs were observed for 30 min, the animals were randomly divided in four groups: 5 animals received via a small catheter (26G) placed proximally to the stenosis, an intra-arterial infusion of human recombinant FVIIai (0.1 mg/kg/min for 10 min); 9 animals received AP-1, a monoclonal antibody against rabbit TF (0.1 mg/kg i.v. bolus); 7 animals received ridogrel, a dual thromboxane A2 synthetase inhibitor and thromboxane A2 receptor antagonist (10 mg/kg i.v. bolus); finally, 8 rabbits received aurintrycarboxilic acid (ATA), an inhibitor of platelet glycoprotein Ib/von Willebrand factor interaction (10 mg/kg i.v. bolus). FVIIai abolished CFVs in 5 of 5 animals (CFV frequency minutes 0 cycles/hour; p < 0.05; carotid blood flow velocity minutes 106 +/- 9% of the baseline values; NS vs baseline). AP-1 abolished CFVs in 7 of 9 animals (CFV frequency minutes 0 cycles/hour; p < 0.05; carotid blood flow velocity minutes 58 +/- 35% of the baseline values; NS vs baseline). Finally, in all the animals receiving ridogrel or ATA CFVs were abolished (CFV frequency 0 cycles/hour; p < 0.05 in both groups; carotid blood flow velocity, respectively 62 +/- 32 and 66 +/- 40% of the baseline values; NS vs baseline in both groups). Thirty minutes following inhibition of CFVs, in the FVIIai treated rabbits, human recombinant FVIIa was infused, via the small catheter placed proximally to the stenosis, at the dose of 0.1 mg/kg/min for 10 min. In the other three groups, FVIIa, at the same dose, was infused i.v. Infusion of FVIIa restored CFVs in all FVIIai treated animals and in 6 of 7 AP-1 treated animals, thus indicating that AP-1 and FVIIai bindings to TF was competitive and was replaced by FVIIa. Infusion of FVIIa failed to restore CFVs in ridogrel e ATA treated rabbits (1 of 7 and 0 of 8 rabbits, respectively), showing that activation of extrinsic coagulation by FVIIa was overcome by inhibition of platelet function. Activated partial thromboplastin time, and ex vivo platelet aggregation in response to ADP and thrombin, were not different after FVIIai infusion, while prothrombin time was slightly but significantly prolonged as compared to baseline values. Thus, FVII-VIIa plays an important role in initiating thrombus formation in vivo. Administration of FVIIai exerts a potent antithrombotic effects in this model without affecting systemic coagulation. In addition, in this model platelets exert an important role in arterial thrombosis, since in the presence of inhibition of platelet function, activation of the extrinsic coagulation pathway failed to restore thrombus formation."
],
"offsets": [
[
129,
3787
]
]
}
] | [
{
"id": "8697470_T1",
"type": "CHEMICAL",
"text": [
"aurintrycarboxilic acid"
],
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[
1686,
1709
]
],
"normalized": []
},
{
"id": "8697470_T2",
"type": "CHEMICAL",
"text": [
"ATA"
],
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[
1711,
1714
]
],
"normalized": []
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{
"id": "8697470_T3",
"type": "CHEMICAL",
"text": [
"ATA"
],
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[
2215,
2218
]
],
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},
{
"id": "8697470_T4",
"type": "CHEMICAL",
"text": [
"ATA"
],
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[
2946,
2949
]
],
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},
{
"id": "8697470_T5",
"type": "CHEMICAL",
"text": [
"ADP"
],
"offsets": [
[
3203,
3206
]
],
"normalized": []
},
{
"id": "8697470_T6",
"type": "GENE-Y",
"text": [
"TF"
],
"offsets": [
[
248,
250
]
],
"normalized": []
},
{
"id": "8697470_T7",
"type": "GENE-Y",
"text": [
"human recombinant FVIIai"
],
"offsets": [
[
1382,
1406
]
],
"normalized": []
},
{
"id": "8697470_T8",
"type": "GENE-Y",
"text": [
"factor VII"
],
"offsets": [
[
260,
270
]
],
"normalized": []
},
{
"id": "8697470_T9",
"type": "GENE-Y",
"text": [
"rabbit TF"
],
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[
1490,
1499
]
],
"normalized": []
},
{
"id": "8697470_T10",
"type": "GENE-Y",
"text": [
"thromboxane A2 synthetase"
],
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[
1560,
1585
]
],
"normalized": []
},
{
"id": "8697470_T11",
"type": "GENE-Y",
"text": [
"FVII"
],
"offsets": [
[
272,
276
]
],
"normalized": []
},
{
"id": "8697470_T12",
"type": "GENE-Y",
"text": [
"thromboxane A2 receptor"
],
"offsets": [
[
1600,
1623
]
],
"normalized": []
},
{
"id": "8697470_T13",
"type": "GENE-Y",
"text": [
"activated FVII"
],
"offsets": [
[
281,
295
]
],
"normalized": []
},
{
"id": "8697470_T14",
"type": "GENE-N",
"text": [
"glycoprotein Ib"
],
"offsets": [
[
1742,
1757
]
],
"normalized": []
},
{
"id": "8697470_T15",
"type": "GENE-Y",
"text": [
"von Willebrand factor"
],
"offsets": [
[
1758,
1779
]
],
"normalized": []
},
{
"id": "8697470_T16",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
297,
302
]
],
"normalized": []
},
{
"id": "8697470_T17",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
1815,
1821
]
],
"normalized": []
},
{
"id": "8697470_T18",
"type": "GENE-Y",
"text": [
"FX"
],
"offsets": [
[
346,
348
]
],
"normalized": []
},
{
"id": "8697470_T19",
"type": "GENE-Y",
"text": [
"FIX"
],
"offsets": [
[
353,
356
]
],
"normalized": []
},
{
"id": "8697470_T20",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
2469,
2475
]
],
"normalized": []
},
{
"id": "8697470_T21",
"type": "GENE-Y",
"text": [
"human recombinant FVIIa"
],
"offsets": [
[
2493,
2516
]
],
"normalized": []
},
{
"id": "8697470_T22",
"type": "GENE-Y",
"text": [
"thrombin"
],
"offsets": [
[
380,
388
]
],
"normalized": []
},
{
"id": "8697470_T23",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
2656,
2661
]
],
"normalized": []
},
{
"id": "8697470_T24",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
2710,
2715
]
],
"normalized": []
},
{
"id": "8697470_T25",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
2737,
2743
]
],
"normalized": []
},
{
"id": "8697470_T26",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
2826,
2832
]
],
"normalized": []
},
{
"id": "8697470_T27",
"type": "GENE-Y",
"text": [
"TF"
],
"offsets": [
[
2845,
2847
]
],
"normalized": []
},
{
"id": "8697470_T28",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
2884,
2889
]
],
"normalized": []
},
{
"id": "8697470_T29",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
2903,
2908
]
],
"normalized": []
},
{
"id": "8697470_T30",
"type": "GENE-Y",
"text": [
"FVIIa"
],
"offsets": [
[
3061,
3066
]
],
"normalized": []
},
{
"id": "8697470_T31",
"type": "GENE-Y",
"text": [
"FVII"
],
"offsets": [
[
435,
439
]
],
"normalized": []
},
{
"id": "8697470_T32",
"type": "GENE-Y",
"text": [
"thrombin"
],
"offsets": [
[
3211,
3219
]
],
"normalized": []
},
{
"id": "8697470_T33",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
3246,
3252
]
],
"normalized": []
},
{
"id": "8697470_T34",
"type": "GENE-Y",
"text": [
"TF"
],
"offsets": [
[
451,
453
]
],
"normalized": []
},
{
"id": "8697470_T35",
"type": "GENE-N",
"text": [
"FVII-VIIa"
],
"offsets": [
[
3365,
3374
]
],
"normalized": []
},
{
"id": "8697470_T36",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
3459,
3465
]
],
"normalized": []
},
{
"id": "8697470_T37",
"type": "GENE-Y",
"text": [
"active site-blocked FVIIa"
],
"offsets": [
[
494,
519
]
],
"normalized": []
},
{
"id": "8697470_T38",
"type": "GENE-Y",
"text": [
"FVIIai"
],
"offsets": [
[
521,
527
]
],
"normalized": []
},
{
"id": "8697470_T39",
"type": "GENE-Y",
"text": [
"tissue factor"
],
"offsets": [
[
181,
194
]
],
"normalized": []
},
{
"id": "8697470_T40",
"type": "GENE-Y",
"text": [
"human FVIIa"
],
"offsets": [
[
773,
784
]
],
"normalized": []
},
{
"id": "8697470_T41",
"type": "GENE-Y",
"text": [
"TF"
],
"offsets": [
[
196,
198
]
],
"normalized": []
},
{
"id": "8697470_T42",
"type": "GENE-Y",
"text": [
"Inactivated factor VII"
],
"offsets": [
[
1,
23
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "8697470_0",
"type": "INHIBITOR",
"arg1_id": "8697470_T2",
"arg2_id": "8697470_T14",
"normalized": []
},
{
"id": "8697470_1",
"type": "INHIBITOR",
"arg1_id": "8697470_T1",
"arg2_id": "8697470_T14",
"normalized": []
},
{
"id": "8697470_2",
"type": "INHIBITOR",
"arg1_id": "8697470_T1",
"arg2_id": "8697470_T15",
"normalized": []
},
{
"id": "8697470_3",
"type": "INHIBITOR",
"arg1_id": "8697470_T2",
"arg2_id": "8697470_T15",
"normalized": []
}
] |
23323829 | 23323829 | [
{
"id": "23323829_title",
"type": "title",
"text": [
"Design and application of anthracene derivative with aggregation-induced emission charateristics for visualization and monitoring of erythropoietin unfolding."
],
"offsets": [
[
0,
158
]
]
},
{
"id": "23323829_abstract",
"type": "abstract",
"text": [
"Erythropoietin (EPO) is an attractive protein-unfolding/folding model because of its high degree of unfolding and folding reversibility and intermediate size. Due to its function for regulating red blood cell production by stimulating late erythroid precursor cells, EPO presents obvious values to biological research. A nonemissive anthracene derivative, that is 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene sodium salt (BSPSA), with aggregation-induced emission (AIE) charateristics shows a novel phenomenon of AIE when EPO is added. The AIE biosensor for EPO shows the limit of detection is 1 × 10(-9) M. Utilizing the AIE feature of BSPSA, the unfolding process of EPO using guanidine hydrochloride is monitored, which indicates three steps for the folding structures of EPO to transform to random coil. Computational modeling suggests that the BSPSA luminogens prefer docking in the hydrophobic cavity in the EPO folding structures, and the assembly of BSPSA in this cavity makes the AIE available, making the monitoring of unfolding of EPO possible."
],
"offsets": [
[
159,
1220
]
]
}
] | [
{
"id": "23323829_T1",
"type": "CHEMICAL",
"text": [
"anthracene"
],
"offsets": [
[
492,
502
]
],
"normalized": []
},
{
"id": "23323829_T2",
"type": "CHEMICAL",
"text": [
"9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene sodium salt"
],
"offsets": [
[
523,
585
]
],
"normalized": []
},
{
"id": "23323829_T3",
"type": "CHEMICAL",
"text": [
"BSPSA"
],
"offsets": [
[
587,
592
]
],
"normalized": []
},
{
"id": "23323829_T4",
"type": "CHEMICAL",
"text": [
"BSPSA"
],
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[
802,
807
]
],
"normalized": []
},
{
"id": "23323829_T5",
"type": "CHEMICAL",
"text": [
"guanidine hydrochloride"
],
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[
844,
867
]
],
"normalized": []
},
{
"id": "23323829_T6",
"type": "CHEMICAL",
"text": [
"BSPSA"
],
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[
1014,
1019
]
],
"normalized": []
},
{
"id": "23323829_T7",
"type": "CHEMICAL",
"text": [
"BSPSA"
],
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[
1123,
1128
]
],
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},
{
"id": "23323829_T8",
"type": "CHEMICAL",
"text": [
"anthracene"
],
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[
26,
36
]
],
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},
{
"id": "23323829_T9",
"type": "GENE-Y",
"text": [
"Erythropoietin"
],
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[
159,
173
]
],
"normalized": []
},
{
"id": "23323829_T10",
"type": "GENE-Y",
"text": [
"EPO"
],
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[
1207,
1210
]
],
"normalized": []
},
{
"id": "23323829_T11",
"type": "GENE-Y",
"text": [
"EPO"
],
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[
175,
178
]
],
"normalized": []
},
{
"id": "23323829_T12",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
426,
429
]
],
"normalized": []
},
{
"id": "23323829_T13",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
687,
690
]
],
"normalized": []
},
{
"id": "23323829_T14",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
723,
726
]
],
"normalized": []
},
{
"id": "23323829_T15",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
834,
837
]
],
"normalized": []
},
{
"id": "23323829_T16",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
940,
943
]
],
"normalized": []
},
{
"id": "23323829_T17",
"type": "GENE-Y",
"text": [
"EPO"
],
"offsets": [
[
1079,
1082
]
],
"normalized": []
},
{
"id": "23323829_T18",
"type": "GENE-Y",
"text": [
"erythropoietin"
],
"offsets": [
[
133,
147
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23323829_0",
"type": "DIRECT-REGULATOR",
"arg1_id": "23323829_T6",
"arg2_id": "23323829_T17",
"normalized": []
},
{
"id": "23323829_1",
"type": "DIRECT-REGULATOR",
"arg1_id": "23323829_T7",
"arg2_id": "23323829_T10",
"normalized": []
}
] |
23404739 | 23404739 | [
{
"id": "23404739_title",
"type": "title",
"text": [
"Optimization of marine triterpene sipholenols as inhibitors of breast cancer migration and invasion."
],
"offsets": [
[
0,
100
]
]
},
{
"id": "23404739_abstract",
"type": "abstract",
"text": [
"Sipholenol A, a sipholane triterpene isolated from the Red Sea sponge Callyspongia siphonella, has the ability to reverse multidrug resistance in cancer cells that overexpress P-glycoprotein (P-gp). Here, the antimigratory activity of sipholenol A and analogues are reported against the highly metastatic human breast cancer cell line MDA-MB-231 in a wound-healing assay. Sipholenol A and sipholenone A were semisynthetically optimized using ligand-based strategies to generate structurally diverse analogues in an attempt to maximize their antimigratory activity. A total of 22 semisynthetic ester, ether, oxime, and carbamate analogues were generated and identified by extensive one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry analyses. Sipholenol A 4β-4-chlorobenzoate and 19,20-anhydrosipholenol A 4β-4-chlorobenzoate esters were the most potent of all tested analogues in the wound-healing assay, with IC(50) values of 5.3 and 5.9 μM, respectively. Generally, ester derivatives showed better antimigratory activities than the carbamate analogues. A KINOMEscan of 19,20-anhydrosipholenol A 4β-benzoate ester against 451 human protein kinases identified protein tyrosine kinase 6 (PTK6) as a potential target. In breast tumor cells, PTK6 promotes growth factor signaling and migration, and as such the semisynthetic sipholanes were evaluated for their ability to inhibit PTK6 phosphorylation in vitro. The two analogues with the highest antimigratory activities, sipholenol A 4β-4-chlorobenzoate and 19,20-anhydrosipholenol A 4β-4-chlorobenzoate esters, also exhibited the most potent inhibition of PTK6 phosphorylation inhibition. None of the compounds exhibited cytotoxicity in a normal epithelial breast cell line. These derivatives were evaluated in an in vitro invasion assay, where sipholenol A succinate potently inhibited MDA-MB-231 cell invasion at 10 μM. These results highlight sipholane triterpenoids as novel antimigratory marine natural products with potential for further development as agents for the control of metastatic breast malignancies."
],
"offsets": [
[
101,
2195
]
]
}
] | [
{
"id": "23404739_T1",
"type": "CHEMICAL",
"text": [
"Sipholenol A"
],
"offsets": [
[
101,
113
]
],
"normalized": []
},
{
"id": "23404739_T2",
"type": "CHEMICAL",
"text": [
"carbamate"
],
"offsets": [
[
1164,
1173
]
],
"normalized": []
},
{
"id": "23404739_T3",
"type": "CHEMICAL",
"text": [
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1452,
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473,
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490,
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694,
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701,
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708,
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719,
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872,
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909,
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"P-gp"
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293,
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],
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}
] | [] | [] | [
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}
] |
23258671 | 23258671 | [
{
"id": "23258671_title",
"type": "title",
"text": [
"Super-stable ultrafine beta-tungsten nanocrystals with metastable phase and related magnetism."
],
"offsets": [
[
0,
94
]
]
},
{
"id": "23258671_abstract",
"type": "abstract",
"text": [
"Ultrafine tungsten nanocrystals (average size of 3 nm) with a metastable phase (beta-tungsten with A15 structure, β-W) have been prepared by laser ablation of tungsten in liquid nitrogen. The as-prepared metastable nanocrystals exhibited super-stablity, and can keep the same metastable structure over a period of 6 months at room temperature. This super-stability is attributed to the nanosized confinement effect of ultrafine nanocrystals. The magnetism measurements showed that the β-W nanocrystals have weak ferromagnetic properties at 2 K, which may arise from surface defects and unpaired electrons on the surface of the ultrafine nanocrystals. These findings provided useful information for the application of ultrafine β-W nanocrystals in microelectronics and spintronics."
],
"offsets": [
[
95,
875
]
]
}
] | [
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"id": "23258671_T1",
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105,
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]
],
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],
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254,
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]
],
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},
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"id": "23258671_T4",
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"text": [
"nitrogen"
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273,
281
]
],
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},
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"W"
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582,
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"W"
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"beta-tungsten"
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175,
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]
],
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"id": "23258671_T8",
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23,
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]
],
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}
] | [] | [] | [] |
10403635 | 10403635 | [
{
"id": "10403635_title",
"type": "title",
"text": [
"Success of pyridostigmine, physostigmine, eptastigmine and phosphotriesterase treatments in acute sarin intoxication."
],
"offsets": [
[
0,
117
]
]
},
{
"id": "10403635_abstract",
"type": "abstract",
"text": [
"The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (AChE) in the nervous system, which leads to increased synaptic acetylcholine levels. The protective actions of intravenously (i.v.) administered pyridostigmine, physostigmine, eptastigmine, and an organophosphate hydrolase, phosphotriesterase, in acute sarin intoxication were studied in mice. The acute intragastric (i.g.) toxicity (LD50) of sarin with and without the pretreatments was tested by the up-and-down method. The mice received pyridostigmine (0.06 mg/kg body weight), physostigmine (0.09 mg/kg body weight), the physostigmine derivative eptastigmine (0.90 mg/kg body weight) or phosphotriesterase (104 U/g, 10.7 microg/g body weight) 10 min prior to the i.g. administration of sarin. Physostigmine was also administered with phosphotriesterase. Phosphotriesterase was the most effective antidote in sarin intoxication. The LD50 value for sarin increased 3.4-fold in mice receiving phosphotriesterase. Physostigmine was the most effective carbamate in sarin exposure. The protective ratios of physostigmine and pyridostigmine were 1.5- and 1.2-1.3-fold, respectively. Eptastigmine did not give any protection against sarin toxicity. Both the phosphotriesterase and physostigmine treatments protected the brain AChE activities measured 24 h after sarin exposure. In phosphotriesterase and physostigmine-treated mice, a 4- and 2-fold higher sarin dose, respectively, was needed to cause a 50% inhibition of brain AChE activity. Moreover, the combination of phosphotriesterase-physostigmine increased the LD50 value for sarin 4.3-fold. The animals pretreated with phosphotriesterase-ephysostigmine tolerated four times the lethal dose in control animals, furthermore their survival time was 2-3 h in comparison to 20 min in controls. In conclusion, phosphotriesterase and physostigmine were the most effective treatments against sarin intoxication. However, eptastigmine did not provide any protection against sarin toxicity."
],
"offsets": [
[
118,
2182
]
]
}
] | [
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"id": "10403635_T1",
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]
],
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},
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1199,
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]
],
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},
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"id": "10403635_T3",
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"sarin"
],
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1212,
1217
]
],
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1253,
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]
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},
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"id": "10403635_T5",
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"pyridostigmine"
],
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1271,
1285
]
],
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"Eptastigmine"
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]
],
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},
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"id": "10403635_T7",
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"sarin"
],
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1377,
1382
]
],
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},
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"physostigmine"
],
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1425,
1438
]
],
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},
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"id": "10403635_T9",
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"sarin"
],
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1506,
1511
]
],
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},
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],
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1548,
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]
],
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},
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"sarin"
],
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1599,
1604
]
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1734,
1747
]
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"sarin"
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1777,
1782
]
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},
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"ephysostigmine"
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1840,
1854
]
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},
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"physostigmine"
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2029,
2042
]
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},
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"acetylcholine"
],
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311,
324
]
],
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},
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"sarin"
],
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2086,
2091
]
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},
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"eptastigmine"
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2115,
2127
]
],
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},
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"sarin"
],
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[
2167,
2172
]
],
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},
{
"id": "10403635_T20",
"type": "CHEMICAL",
"text": [
"organophosphorus"
],
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[
140,
156
]
],
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},
{
"id": "10403635_T21",
"type": "CHEMICAL",
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"pyridostigmine"
],
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[
393,
407
]
],
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},
{
"id": "10403635_T22",
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"physostigmine"
],
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409,
422
]
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},
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"id": "10403635_T23",
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"eptastigmine"
],
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424,
436
]
],
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},
{
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"organophosphate"
],
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[
445,
460
]
],
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},
{
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"sarin"
],
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501,
506
]
],
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},
{
"id": "10403635_T26",
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"sarin"
],
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591,
596
]
],
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},
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"id": "10403635_T27",
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"pyridostigmine"
],
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[
688,
702
]
],
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},
{
"id": "10403635_T28",
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"physostigmine"
],
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[
729,
742
]
],
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},
{
"id": "10403635_T29",
"type": "CHEMICAL",
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"physostigmine"
],
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[
773,
786
]
],
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},
{
"id": "10403635_T30",
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"eptastigmine"
],
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[
798,
810
]
],
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},
{
"id": "10403635_T31",
"type": "CHEMICAL",
"text": [
"sarin"
],
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[
938,
943
]
],
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},
{
"id": "10403635_T32",
"type": "CHEMICAL",
"text": [
"Physostigmine"
],
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[
945,
958
]
],
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},
{
"id": "10403635_T33",
"type": "CHEMICAL",
"text": [
"sarin"
],
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[
1060,
1065
]
],
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},
{
"id": "10403635_T34",
"type": "CHEMICAL",
"text": [
"sarin"
],
"offsets": [
[
1099,
1104
]
],
"normalized": []
},
{
"id": "10403635_T35",
"type": "CHEMICAL",
"text": [
"pyridostigmine"
],
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[
11,
25
]
],
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},
{
"id": "10403635_T36",
"type": "CHEMICAL",
"text": [
"physostigmine"
],
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[
27,
40
]
],
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},
{
"id": "10403635_T37",
"type": "CHEMICAL",
"text": [
"eptastigmine"
],
"offsets": [
[
42,
54
]
],
"normalized": []
},
{
"id": "10403635_T38",
"type": "CHEMICAL",
"text": [
"sarin"
],
"offsets": [
[
98,
103
]
],
"normalized": []
},
{
"id": "10403635_T39",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
1142,
1160
]
],
"normalized": []
},
{
"id": "10403635_T40",
"type": "GENE-N",
"text": [
"acetylcholinesterase"
],
"offsets": [
[
226,
246
]
],
"normalized": []
},
{
"id": "10403635_T41",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
1402,
1420
]
],
"normalized": []
},
{
"id": "10403635_T42",
"type": "GENE-N",
"text": [
"AChE"
],
"offsets": [
[
248,
252
]
],
"normalized": []
},
{
"id": "10403635_T43",
"type": "GENE-Y",
"text": [
"AChE"
],
"offsets": [
[
1470,
1474
]
],
"normalized": []
},
{
"id": "10403635_T44",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
1525,
1543
]
],
"normalized": []
},
{
"id": "10403635_T45",
"type": "GENE-Y",
"text": [
"AChE"
],
"offsets": [
[
1671,
1675
]
],
"normalized": []
},
{
"id": "10403635_T46",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
1715,
1733
]
],
"normalized": []
},
{
"id": "10403635_T47",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
1821,
1839
]
],
"normalized": []
},
{
"id": "10403635_T48",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
2006,
2024
]
],
"normalized": []
},
{
"id": "10403635_T49",
"type": "GENE-N",
"text": [
"organophosphate hydrolase"
],
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445,
470
]
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"id": "10403635_T50",
"type": "GENE-N",
"text": [
"phosphotriesterase"
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472,
490
]
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"normalized": []
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"id": "10403635_T51",
"type": "GENE-N",
"text": [
"phosphotriesterase"
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839,
857
]
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"id": "10403635_T52",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
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986,
1004
]
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},
{
"id": "10403635_T53",
"type": "GENE-N",
"text": [
"Phosphotriesterase"
],
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1006,
1024
]
],
"normalized": []
},
{
"id": "10403635_T54",
"type": "GENE-N",
"text": [
"phosphotriesterase"
],
"offsets": [
[
59,
77
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "10403635_0",
"type": "INHIBITOR",
"arg1_id": "10403635_T20",
"arg2_id": "10403635_T40",
"normalized": []
},
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},
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"id": "10403635_2",
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},
{
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},
{
"id": "10403635_4",
"type": "INHIBITOR",
"arg1_id": "10403635_T11",
"arg2_id": "10403635_T45",
"normalized": []
}
] |
23585380 | 23585380 | [
{
"id": "23585380_title",
"type": "title",
"text": [
"Dual Growth Factor Delivery Using Biocompatible Core-Shell Microcapsules for Angiogenesis."
],
"offsets": [
[
0,
90
]
]
},
{
"id": "23585380_abstract",
"type": "abstract",
"text": [
"An optimized electrodropping system produces homogeneous core-shell microcapsules (C-S MCs) by using poly(L-lactic-co-glycolic acid) (PLGA) and alginate. Fluorescence imaging clearly shows the C-S domain in the MC. For release control, the use of high-molecular-weight PLGA (HMW 270 000) restrains the initial burst release of protein compared to that of low-MW PLGA (LMW 40 000). Layer-by-layer (LBL) assembly of chitosan and alginate on MCs is also useful in controlling the release profile of biomolecules. LBL (7-layer) treatment is effective in suppressing the initial burst release of protein compared to no LBL (0-layer). The difference of cumulative albumin release between HMW (7-layer LBL) and LMW (0-layer LBL) PLGA is determined to be more than 40% on day 5. When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core PLGA. As for the angiogenic potential of MC GFs with human umbilical vein endothelial cells (HUVECs), the fluorescence signal of CD31+ suggests that the angiogenic sprout of ECs is more active in MC-mediated GF delivery than conventional GF delivery, and this difference is significant, based on the number of capillary branches in the unit area. This study demonstrates that the fabrication of biocompatible C-S MCs is possible, and that the release control of biomolecules is adjustable. Furthermore, MC-mediated GFs remain in an active form and can upregulate the angiogenic activity of ECs."
],
"offsets": [
[
91,
1849
]
]
}
] | [
{
"id": "23585380_T1",
"type": "CHEMICAL",
"text": [
"poly(L-lactic-co-glycolic acid)"
],
"offsets": [
[
192,
223
]
],
"normalized": []
},
{
"id": "23585380_T2",
"type": "CHEMICAL",
"text": [
"PLGA"
],
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[
1218,
1222
]
],
"normalized": []
},
{
"id": "23585380_T3",
"type": "CHEMICAL",
"text": [
"PLGA"
],
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[
1255,
1259
]
],
"normalized": []
},
{
"id": "23585380_T4",
"type": "CHEMICAL",
"text": [
"PLGA"
],
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225,
229
]
],
"normalized": []
},
{
"id": "23585380_T5",
"type": "CHEMICAL",
"text": [
"PLGA"
],
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[
360,
364
]
],
"normalized": []
},
{
"id": "23585380_T6",
"type": "CHEMICAL",
"text": [
"PLGA"
],
"offsets": [
[
453,
457
]
],
"normalized": []
},
{
"id": "23585380_T7",
"type": "CHEMICAL",
"text": [
"PLGA"
],
"offsets": [
[
813,
817
]
],
"normalized": []
},
{
"id": "23585380_T8",
"type": "GENE-N",
"text": [
"PDGF"
],
"offsets": [
[
1100,
1104
]
],
"normalized": []
},
{
"id": "23585380_T9",
"type": "GENE-Y",
"text": [
"CD31"
],
"offsets": [
[
1384,
1388
]
],
"normalized": []
},
{
"id": "23585380_T10",
"type": "GENE-N",
"text": [
"platelet-derived GF"
],
"offsets": [
[
913,
932
]
],
"normalized": []
},
{
"id": "23585380_T11",
"type": "GENE-N",
"text": [
"PDGF"
],
"offsets": [
[
934,
938
]
],
"normalized": []
},
{
"id": "23585380_T12",
"type": "GENE-N",
"text": [
"vascular endothelial GF"
],
"offsets": [
[
944,
967
]
],
"normalized": []
},
{
"id": "23585380_T13",
"type": "GENE-N",
"text": [
"VEGF"
],
"offsets": [
[
969,
973
]
],
"normalized": []
},
{
"id": "23585380_T14",
"type": "GENE-N",
"text": [
"VEGF"
],
"offsets": [
[
1053,
1057
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23585380_0",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23585380_T2",
"arg2_id": "23585380_T14",
"normalized": []
},
{
"id": "23585380_1",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23585380_T2",
"arg2_id": "23585380_T8",
"normalized": []
},
{
"id": "23585380_2",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23585380_T3",
"arg2_id": "23585380_T14",
"normalized": []
},
{
"id": "23585380_3",
"type": "INDIRECT-UPREGULATOR",
"arg1_id": "23585380_T3",
"arg2_id": "23585380_T8",
"normalized": []
}
] |
15276688 | 15276688 | [
{
"id": "15276688_title",
"type": "title",
"text": [
"Extracellular serotonin, dopamine and glutamate levels are elevated in the hypothalamus in a serotonin syndrome animal model induced by tranylcypromine and fluoxetine."
],
"offsets": [
[
0,
167
]
]
},
{
"id": "15276688_abstract",
"type": "abstract",
"text": [
"Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. The present study was undertaken to demonstrate that nervous systems other than the 5-HT system also participate in the pathophysiology of 5-HT syndrome. Concentrations of 5-HT, dopamine (DA) and glutamate in the hypothalamus were measured in two different 5-HT syndrome animal models using a microdialysis technique. The first model was induced by tranylcypromine, a nonselective monoamine oxidase (MAO) inhibitor (3.5 mg/kg) and fluoxetine, a selective serotonin reuptake inhibitor (SSRI) (10 mg/kg). The second model was induced by clorgyline, an MAO-A inhibitor (1.2 mg/kg) and 5-hydroxy-L-tryptophan, a precursor of 5-HT (5-HTP) (80 mg/kg). In the first model, the levels of 5-HT and DA increased by 40-fold and 44-fold, respectively, compared with the preadministration levels. In the second model, the concentrations of 5-HT increased by up to 140-fold, whereas DA levels increased by only 10-fold, of the preadministration levels. Although the level of glutamate in the second model barely changed, a delayed increase in the glutamate level was observed in the first model. These findings suggest that not only hyperactivity of the 5-HT system, but also hyperactivity of the DA system, are present in 5-HT syndrome, and that the glutamatergic system is influenced in some 5-HT syndrome cases in which the DA concentration markedly increases."
],
"offsets": [
[
168,
1636
]
]
}
] | [
{
"id": "15276688_T1",
"type": "CHEMICAL",
"text": [
"Serotonin"
],
"offsets": [
[
168,
177
]
],
"normalized": []
},
{
"id": "15276688_T2",
"type": "CHEMICAL",
"text": [
"glutamate"
],
"offsets": [
[
1248,
1257
]
],
"normalized": []
},
{
"id": "15276688_T3",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
179,
183
]
],
"normalized": []
},
{
"id": "15276688_T4",
"type": "CHEMICAL",
"text": [
"glutamate"
],
"offsets": [
[
1320,
1329
]
],
"normalized": []
},
{
"id": "15276688_T5",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
1427,
1431
]
],
"normalized": []
},
{
"id": "15276688_T6",
"type": "CHEMICAL",
"text": [
"DA"
],
"offsets": [
[
1470,
1472
]
],
"normalized": []
},
{
"id": "15276688_T7",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
1496,
1500
]
],
"normalized": []
},
{
"id": "15276688_T8",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
1567,
1571
]
],
"normalized": []
},
{
"id": "15276688_T9",
"type": "CHEMICAL",
"text": [
"DA"
],
"offsets": [
[
1600,
1602
]
],
"normalized": []
},
{
"id": "15276688_T10",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
371,
375
]
],
"normalized": []
},
{
"id": "15276688_T11",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
426,
430
]
],
"normalized": []
},
{
"id": "15276688_T12",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
459,
463
]
],
"normalized": []
},
{
"id": "15276688_T13",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
465,
473
]
],
"normalized": []
},
{
"id": "15276688_T14",
"type": "CHEMICAL",
"text": [
"DA"
],
"offsets": [
[
475,
477
]
],
"normalized": []
},
{
"id": "15276688_T15",
"type": "CHEMICAL",
"text": [
"glutamate"
],
"offsets": [
[
483,
492
]
],
"normalized": []
},
{
"id": "15276688_T16",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
544,
548
]
],
"normalized": []
},
{
"id": "15276688_T17",
"type": "CHEMICAL",
"text": [
"tranylcypromine"
],
"offsets": [
[
636,
651
]
],
"normalized": []
},
{
"id": "15276688_T18",
"type": "CHEMICAL",
"text": [
"monoamine"
],
"offsets": [
[
668,
677
]
],
"normalized": []
},
{
"id": "15276688_T19",
"type": "CHEMICAL",
"text": [
"fluoxetine"
],
"offsets": [
[
718,
728
]
],
"normalized": []
},
{
"id": "15276688_T20",
"type": "CHEMICAL",
"text": [
"serotonin"
],
"offsets": [
[
742,
751
]
],
"normalized": []
},
{
"id": "15276688_T21",
"type": "CHEMICAL",
"text": [
"clorgyline"
],
"offsets": [
[
822,
832
]
],
"normalized": []
},
{
"id": "15276688_T22",
"type": "CHEMICAL",
"text": [
"5-hydroxy-L-tryptophan"
],
"offsets": [
[
869,
891
]
],
"normalized": []
},
{
"id": "15276688_T23",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
908,
912
]
],
"normalized": []
},
{
"id": "15276688_T24",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
967,
971
]
],
"normalized": []
},
{
"id": "15276688_T25",
"type": "CHEMICAL",
"text": [
"DA"
],
"offsets": [
[
976,
978
]
],
"normalized": []
},
{
"id": "15276688_T26",
"type": "CHEMICAL",
"text": [
"5-HT"
],
"offsets": [
[
1114,
1118
]
],
"normalized": []
},
{
"id": "15276688_T27",
"type": "CHEMICAL",
"text": [
"DA"
],
"offsets": [
[
1156,
1158
]
],
"normalized": []
},
{
"id": "15276688_T28",
"type": "CHEMICAL",
"text": [
"tranylcypromine"
],
"offsets": [
[
136,
151
]
],
"normalized": []
},
{
"id": "15276688_T29",
"type": "CHEMICAL",
"text": [
"serotonin"
],
"offsets": [
[
14,
23
]
],
"normalized": []
},
{
"id": "15276688_T30",
"type": "CHEMICAL",
"text": [
"fluoxetine"
],
"offsets": [
[
156,
166
]
],
"normalized": []
},
{
"id": "15276688_T31",
"type": "CHEMICAL",
"text": [
"dopamine"
],
"offsets": [
[
25,
33
]
],
"normalized": []
},
{
"id": "15276688_T32",
"type": "CHEMICAL",
"text": [
"glutamate"
],
"offsets": [
[
38,
47
]
],
"normalized": []
},
{
"id": "15276688_T33",
"type": "CHEMICAL",
"text": [
"serotonin"
],
"offsets": [
[
93,
102
]
],
"normalized": []
},
{
"id": "15276688_T34",
"type": "GENE-N",
"text": [
"monoamine oxidase"
],
"offsets": [
[
668,
685
]
],
"normalized": []
},
{
"id": "15276688_T35",
"type": "GENE-N",
"text": [
"MAO"
],
"offsets": [
[
687,
690
]
],
"normalized": []
},
{
"id": "15276688_T36",
"type": "GENE-Y",
"text": [
"MAO-A"
],
"offsets": [
[
837,
842
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "15276688_0",
"type": "INHIBITOR",
"arg1_id": "15276688_T17",
"arg2_id": "15276688_T34",
"normalized": []
},
{
"id": "15276688_1",
"type": "INHIBITOR",
"arg1_id": "15276688_T17",
"arg2_id": "15276688_T35",
"normalized": []
},
{
"id": "15276688_2",
"type": "INHIBITOR",
"arg1_id": "15276688_T21",
"arg2_id": "15276688_T36",
"normalized": []
}
] |
15561708 | 15561708 | [
{
"id": "15561708_title",
"type": "title",
"text": [
"Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration."
],
"offsets": [
[
0,
146
]
]
},
{
"id": "15561708_abstract",
"type": "abstract",
"text": [
"The molybdenum cofactor sulfurase ABA3 from Arabidopsis thaliana specifically regulates the activity of the molybdenum enzymes aldehyde oxidase and xanthine dehydrogenase by converting their molybdenum cofactor from the desulfo-form into the sulfo-form. ABA3 is a two-domain protein with an NH2-terminal domain sharing significant similarities to NifS proteins that catalyze the decomposition of l-cysteine to l-alanine and elemental sulfur for iron-sulfur cluster synthesis. Although different in its physiological function, the mechanism of ABA3 for sulfur mobilization was found to be similar to NifS proteins. The protein binds a pyridoxal phosphate cofactor and a substrate-derived persulfide intermediate, and site-directed mutagenesis of strictly conserved binding sites for the cofactor and the persulfide demonstrated that they are essential for molybdenum cofactor sulfurase activity. In vitro, the NifS-like domain of ABA3 activates aldehyde oxidase and xanthine dehydrogenase in the absence of the C-terminal domain, but in vivo, the C-terminal domain is required for proper activation of both target enzymes. In addition to its cysteine desulfurase activity, ABA3-NifS also exhibits selenocysteine lyase activity. Although l-selenocysteine is unlikely to be a natural substrate for ABA3, it is decomposed more efficiently than l-cysteine. Besides mitochondrial AtNFS1 and plastidial AtNFS2, which are both proposed to be involved in iron-sulfur cluster formation, ABA3 is proposed to be a third and cytosolic NifS-like cysteine desulfurase in A. thaliana. However, the sulfur transferase activity of ABA3 is used for post-translational activation of molybdenum enzymes rather than for iron-sulfur cluster assembly."
],
"offsets": [
[
147,
1874
]
]
}
] | [
{
"id": "15561708_T1",
"type": "CHEMICAL",
"text": [
"C"
],
"offsets": [
[
1157,
1158
]
],
"normalized": []
},
{
"id": "15561708_T2",
"type": "CHEMICAL",
"text": [
"C"
],
"offsets": [
[
1193,
1194
]
],
"normalized": []
},
{
"id": "15561708_T3",
"type": "CHEMICAL",
"text": [
"molybdenum"
],
"offsets": [
[
255,
265
]
],
"normalized": []
},
{
"id": "15561708_T4",
"type": "CHEMICAL",
"text": [
"cysteine"
],
"offsets": [
[
1288,
1296
]
],
"normalized": []
},
{
"id": "15561708_T5",
"type": "CHEMICAL",
"text": [
"selenocysteine"
],
"offsets": [
[
1343,
1357
]
],
"normalized": []
},
{
"id": "15561708_T6",
"type": "CHEMICAL",
"text": [
"l-selenocysteine"
],
"offsets": [
[
1383,
1399
]
],
"normalized": []
},
{
"id": "15561708_T7",
"type": "CHEMICAL",
"text": [
"aldehyde"
],
"offsets": [
[
274,
282
]
],
"normalized": []
},
{
"id": "15561708_T8",
"type": "CHEMICAL",
"text": [
"l-cysteine"
],
"offsets": [
[
1487,
1497
]
],
"normalized": []
},
{
"id": "15561708_T9",
"type": "CHEMICAL",
"text": [
"iron-sulfur"
],
"offsets": [
[
1593,
1604
]
],
"normalized": []
},
{
"id": "15561708_T10",
"type": "CHEMICAL",
"text": [
"xanthine"
],
"offsets": [
[
295,
303
]
],
"normalized": []
},
{
"id": "15561708_T11",
"type": "CHEMICAL",
"text": [
"cysteine"
],
"offsets": [
[
1679,
1687
]
],
"normalized": []
},
{
"id": "15561708_T12",
"type": "CHEMICAL",
"text": [
"molybdenum"
],
"offsets": [
[
1810,
1820
]
],
"normalized": []
},
{
"id": "15561708_T13",
"type": "CHEMICAL",
"text": [
"iron-sulfur"
],
"offsets": [
[
1845,
1856
]
],
"normalized": []
},
{
"id": "15561708_T14",
"type": "CHEMICAL",
"text": [
"molybdenum"
],
"offsets": [
[
338,
348
]
],
"normalized": []
},
{
"id": "15561708_T15",
"type": "CHEMICAL",
"text": [
"sulfo"
],
"offsets": [
[
389,
394
]
],
"normalized": []
},
{
"id": "15561708_T16",
"type": "CHEMICAL",
"text": [
"NH2"
],
"offsets": [
[
438,
441
]
],
"normalized": []
},
{
"id": "15561708_T17",
"type": "CHEMICAL",
"text": [
"l-cysteine"
],
"offsets": [
[
543,
553
]
],
"normalized": []
},
{
"id": "15561708_T18",
"type": "CHEMICAL",
"text": [
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] |
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Dataset Card for DrugProt
The DrugProt corpus consists of a) expert-labelled chemical and gene mentions, and (b) all binary relationships between them corresponding to a specific set of biologically relevant relation types. The corpus was introduced in context of the BioCreative VII Track 1 (Text mining drug and chemical-protein interactions).
Citation Information
@inproceedings{miranda2021overview,
title={Overview of DrugProt BioCreative VII track: quality evaluation and large scale text mining of \
drug-gene/protein relations},
author={Miranda, Antonio and Mehryary, Farrokh and Luoma, Jouni and Pyysalo, Sampo and Valencia, Alfonso \
and Krallinger, Martin},
booktitle={Proceedings of the seventh BioCreative challenge evaluation workshop},
year={2021}
}
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Homepage:
biocreative.bioinformatics.udel.edu
Pubmed:
True
Public:
True
Tasks:
NER,RE
Size of downloaded dataset files:
26.8 MB
Size of the auto-converted Parquet files:
16.1 MB
Number of rows:
8,500
Models trained or fine-tuned on bigbio/drugprot