INT121943

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Context Info
Confidence 0.68
First Reported 2004
Last Reported 2011
Negated 2
Speculated 2
Reported most in Body
Documents 64
Total Number 67
Disease Relevance 19.22
Pain Relevance 8.39

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
bile 5
CAR 2
liver 2
bowel 2
hepatocytes 1
Nr1i2 (Mus musculus)
Pain Link Frequency Relevance Heat
Analgesic 61 99.84 Very High Very High Very High
Paracetamol 18 99.74 Very High Very High Very High
Bile 2319 99.72 Very High Very High Very High
Taxol 118 99.40 Very High Very High Very High
Inflammation 1092 98.56 Very High Very High Very High
methadone 10 98.52 Very High Very High Very High
dexamethasone 118 95.60 Very High Very High Very High
Central nervous system 12 95.40 Very High Very High Very High
antidepressant 177 94.80 High High
palliative 59 91.92 High High
Disease Link Frequency Relevance Heat
Toxicity 242 99.92 Very High Very High Very High
Cancer 1062 99.84 Very High Very High Very High
Endometriosis (extended) 177 99.84 Very High Very High Very High
Rickets 472 99.74 Very High Very High Very High
Breast Cancer 472 99.74 Very High Very High Very High
Apoptosis 295 99.24 Very High Very High Very High
Osteogenic Sarcomas 295 98.80 Very High Very High Very High
Inflammatory Bowel Disease 1894 98.56 Very High Very High Very High
Hepatotoxicity 121 98.56 Very High Very High Very High
Van Bogaert's Disease 59 98.44 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI).
Positive_regulation (Activation) of PXR associated with paracetamol
1) Confidence 0.68 Published 2004 Journal Toxicol. Sci. Section Abstract Doc Link 15456926 Disease Relevance 0.28 Pain Relevance 0.41
Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity.
Positive_regulation (activation) of PXR associated with paracetamol and hepatotoxicity
2) Confidence 0.68 Published 2004 Journal Toxicol. Sci. Section Abstract Doc Link 15456926 Disease Relevance 0.39 Pain Relevance 0.51
Enhanced acetaminophen toxicity by activation of the pregnane X receptor.
Positive_regulation (activation) of pregnane X receptor associated with toxicity and paracetamol
3) Confidence 0.68 Published 2004 Journal Toxicol. Sci. Section Title Doc Link 15456926 Disease Relevance 0.39 Pain Relevance 0.50
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 (activation) of SXR associated with endometriosis (extended)
4) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.64 Pain Relevance 0.06
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 (activation) of SXR
5) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.46 Pain Relevance 0.16
This finding was paradoxical because mice expressing activated SXR have increased GST activity, and GSTs play an important role in detoxification of products from oxidative stress.
Positive_regulation (activated) of SXR associated with stress
6) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.67 Pain Relevance 0
Many other natural products that have been shown to activate SXR include gugulipid, kava kava, paclitaxel, Coleus forskohlii, Hypoxis, Sutherlandia, qing hao, wu wei zi and gan cao.
Positive_regulation (activate) of SXR
7) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.15 Pain Relevance 0.11
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 (activation) of SXR associated with osteogenic sarcomas
8) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.66 Pain Relevance 0.12
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 (activation) of SXR in bowel associated with inflammation
9) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 1.38 Pain Relevance 0.38
They conducted a series of in vitro and in vivo studies which were interpreted as providing evidence that a drug, which can activate SXR is likely to enhance CYP24 expression and the catabolism of 25(OH)D3, leading to vitamin D deficiency.
Positive_regulation (activate) of SXR
10) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.45 Pain Relevance 0.06
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 (activation) of SXR in bile associated with bile
11) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.18 Pain Relevance 0.27
To reveal the mechanism of drug-induced osteomalacia, several groups recently investigated the impact of SXR activation on CYP24 gene expression in vitro and in vivo.
Spec (investigated) Positive_regulation (activation) of SXR associated with rickets
12) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.45 Pain Relevance 0.08
This increases the number of ligands that can activate SXR.
Positive_regulation (activate) of SXR
13) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0 Pain Relevance 0
Activation of SXR has been associated with clinically important drug-drug interactions.
Positive_regulation (Activation) of SXR
14) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 1.20 Pain Relevance 0.21
Interestingly, the compounds which did not cause microtubule stabilization and cytotoxicity also did not activate SXR.
Neg (not) Positive_regulation (activate) of SXR
15) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.27 Pain Relevance 0.04
Considering that SXR is activated by such a wide variety of dietary and xenobiotic chemicals, they also suggest new mechanisms through which diet, chemical exposure, and environment ultimately impact heath and disease.



Positive_regulation (activated) of SXR associated with disease
16) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.42 Pain Relevance 0.05
For example, phenobarbital can also bind to and activate SXR.
Positive_regulation (activate) of SXR
17) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.13 Pain Relevance 0.03
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 (activation) of SXR associated with rickets
18) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.44 Pain Relevance 0.08
SXR can be activated by a range of ligands that is almost as diverse as the substrates of CYP3A4, including many drugs.
Positive_regulation (activated) of SXR
19) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0 Pain Relevance 0
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 (Activation) of SXR
20) Confidence 0.65 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.10 Pain Relevance 0.37

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