INT206949

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Context Info
Confidence 0.57
First Reported 2007
Last Reported 2008
Negated 2
Speculated 0
Reported most in Body
Documents 3
Total Number 5
Disease Relevance 2.50
Pain Relevance 0.45

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)
Anatomy Link Frequency
nucleus 3
bile 2
Nr1i2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Bile 10 98.12 Very High Very High Very High
Kinase C 3 96.20 Very High Very High Very High
Paracetamol 2 56.48 Quite High
cytokine 3 5.00 Very Low Very Low Very Low
ketamine 3 5.00 Very Low Very Low Very Low
anesthesia 3 5.00 Very Low Very Low Very Low
Inflammation 3 5.00 Very Low Very Low Very Low
Inflammatory stimuli 3 5.00 Very Low Very Low Very Low
Inflammatory mediators 3 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Adenovirus Infection 21 99.54 Very High Very High Very High
Hepatotoxicity 59 99.08 Very High Very High Very High
Injury 4 97.48 Very High Very High Very High
Targeted Disruption 3 96.92 Very High Very High Very High
Toxicity 68 96.20 Very High Very High Very High
Repression 10 95.04 Very High Very High Very High
Biliary Cancer 4 94.84 High High
Stress 52 72.24 Quite High
Infection 30 56.48 Quite High
Hepatitis 2 47.36 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The down-regulation of PXR and CAR, along with FXR (Guo et al. 2003), would make the liver more susceptible to bile acid toxicity, which, coupled with the biliary hyperplasia, may exacerbate the hepatotoxic effects of methapyrilene administration.
Regulation (regulation) of PXR in bile associated with toxicity, bile and biliary cancer
1) Confidence 0.57 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852695 Disease Relevance 0.97 Pain Relevance 0.24
The down-regulation of PXR may contribute to the hepatotoxicity of methapyrilene, as the ligand-induced activation of PXR serves to protect against bile acid toxicity resulting from several hepatotoxicants (Staudinger et al. 2001), whereas the resistance to bile acid toxicity is lost in mice lacking PXR (Xie et al. 2000).
Regulation (regulation) of PXR in bile associated with toxicity, bile and hepatotoxicity
2) Confidence 0.42 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852695 Disease Relevance 0.64 Pain Relevance 0.16
If this is the case in vivo, we believe that adenovirus infection did not significantly affect PXR levels because both PKA and PKC are upregulated during adenovirus infection [33,34], keeping the expression of this protein in check except at the 24 hour time point when the balance between the expression of each enzyme might be disrupted since they are each uniquely involved at different stages of virus internalization and trafficking to the nucleus which occur during this timeframe [34].
Neg (not) Regulation (affect) of PXR in nucleus associated with adenovirus infection
3) Confidence 0.14 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.25 Pain Relevance 0.05
Although no appreciable changes in PXR and RXR mRNA levels were detected after administration of any of the vectors studied, post-translational modifications of these proteins and CYP itself such as phosphorylation, ubiquitination and redistribution between the nucleus and cytoplasm in response to virus-induced cell signaling cascades could account for the observed reduction in CYP during adenovirus infection and would not be readily detectable by the techniques used to assess changes in CYP, RXR and PXR described in this manuscript [30-32].
Regulation (changes) of PXR in nucleus associated with adenovirus infection
4) Confidence 0.06 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.25 Pain Relevance 0
Although no appreciable changes in PXR and RXR mRNA levels were detected after administration of any of the vectors studied, post-translational modifications of these proteins and CYP itself such as phosphorylation, ubiquitination and redistribution between the nucleus and cytoplasm in response to virus-induced cell signaling cascades could account for the observed reduction in CYP during adenovirus infection and would not be readily detectable by the techniques used to assess changes in CYP, RXR and PXR described in this manuscript [30-32].
Neg (no) Regulation (changes) of PXR in nucleus associated with adenovirus infection
5) Confidence 0.06 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.38 Pain Relevance 0

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