INT136982

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Context Info
Confidence 0.65
First Reported 2006
Last Reported 2009
Negated 1
Speculated 0
Reported most in Body
Documents 3
Total Number 11
Disease Relevance 4.66
Pain Relevance 2.89

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

nucleus (Nr1i2) DNA binding (Nr1i2)
Anatomy Link Frequency
brain 2
bowel 2
bile 2
CNS 2
Nr1i2 (Mus musculus)
Pain Link Frequency Relevance Heat
methadone 10 100.00 Very High Very High Very High
Inflammation 153 99.96 Very High Very High Very High
Analgesic 11 99.84 Very High Very High Very High
Bile 351 99.68 Very High Very High Very High
Central nervous system 12 96.12 Very High Very High Very High
Antinociceptive 2 91.68 High High
agonist 81 89.52 High High
carbamazepine 9 78.84 Quite High
antagonist 63 78.28 Quite High
antiepileptic Drug 9 76.68 Quite High
Disease Link Frequency Relevance Heat
Osteogenic Sarcomas 45 100.00 Very High Very High Very High
Endometriosis (extended) 27 100.00 Very High Very High Very High
Inflammatory Bowel Disease 288 99.96 Very High Very High Very High
Targeted Disruption 161 98.36 Very High Very High Very High
Cancer 162 97.48 Very High Very High Very High
Toxicity 36 96.80 Very High Very High Very High
Celiac Disease 9 95.56 Very High Very High Very High
Osteoporosis 63 95.20 Very High Very High Very High
Rickets 72 94.72 High High
INFLAMMATION 108 91.36 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Taken together, these lines of evidence show that the osteoprotective action of vitamin K2 is largely mediated through the activation of SXR, and that SXR plays a novel and unexpected role as a mediator of bone homeostasis.
Positive_regulation (mediated) of Positive_regulation (activation) of SXR
1) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.47 Pain Relevance 0.16
Activation of SXR by these sterol compounds induces CYP3A expression and provides an alternative pathway for sterol clearance in CYP27A1 null mice [Dussault et al., 2003; Goodwin et al., 2003].
Positive_regulation (induces) of Positive_regulation (Activation) of SXR
2) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.11 Pain Relevance 0.38
Pascussi et al. first suggested that activation of SXR can enhance the expression of the VDR target gene, CYP24, which would increase the catabolism of 1,25(OH)2D3; thereby, leading to drug-induced osteomalacia [Pascussi et al., 2005].
Positive_regulation (enhance) of Positive_regulation (activation) of SXR associated with rickets
3) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.44 Pain Relevance 0.08
Similarly, activation of SXR in endometrial cancer cell lines by many endocrine-disrupting chemicals has been shown to induce CYP3A4/CYP3A7 expression [Masuyama et al., 2003].
Positive_regulation (induce) of Positive_regulation (activation) of SXR associated with endometriosis (extended)
4) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.71 Pain Relevance 0.06
One implication of this is that activation of SXR and induction of the xenobiotic response will induce metabolism of these chemicals.
Positive_regulation (induce) of Positive_regulation (activation) of SXR
5) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0 Pain Relevance 0.11
An independent study conducted by Gonzales et al. also demonstrated that activation of SXR ameliorates experimentally-induced inflammatory bowel disease via inhibition of NF-?
Positive_regulation (induced) of Positive_regulation (activation) of SXR in bowel associated with inflammation
6) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 1.39 Pain Relevance 0.40
For example, the work done by Baker and coworkers shows that activation of SXR by anti-neoplastic agents in osteosarcoma cell lines induces activity of CYP3A4 and MDR1, which provides a possible mechanism for drug resistance in these cells [Mensah-Osman et al., 2007].
Positive_regulation (induces) of Positive_regulation (activation) of SXR associated with osteogenic sarcomas
7) Confidence 0.47 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.68 Pain Relevance 0.12
Bile acids activate FXR, which downregulates synthesis of bile acids and also leads to the transcriptional activation of SXR, thereby promoting bile acid metabolism.


Positive_regulation (leads) of Positive_regulation (activation) of SXR in bile associated with bile
8) Confidence 0.44 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.18 Pain Relevance 0.27
Thus, hPXR activation in vivo increased P-glycoprotein activity and tightened the blood-brain barrier to methadone, reducing the drug's CNS efficacy.
Positive_regulation (increased) of Positive_regulation (activation) of hPXR in CNS associated with central nervous system and methadone
9) Confidence 0.41 Published 2006 Journal Mol. Pharmacol. Section Abstract Doc Link 16837625 Disease Relevance 0.33 Pain Relevance 0.71
In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation.
Positive_regulation (up-regulation) of Positive_regulation (activation) of pregnane X receptor in brain associated with analgesic and methadone
10) Confidence 0.41 Published 2006 Journal Mol. Pharmacol. Section Title Doc Link 16837625 Disease Relevance 0.21 Pain Relevance 0.56
It was later shown that activation of SXR did not induce CYP24 expression in vitro or in vivo, nor did it transactivate the CYP24 promoter [Zhou et al., 2006a].
Neg (not) Positive_regulation (induce) of Positive_regulation (activation) of SXR
11) Confidence 0.41 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.14 Pain Relevance 0.03

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