INT127037

Context Info Confidence 0.65 First Reported 2005 Last Reported 2010 Negated 1 Speculated 2 Reported most in Body Documents 26 Total Number 28 Disease Relevance 16.08 Pain Relevance 6.84

isomerase activity (Ppig) protein folding (Ppig) nucleus (Ppig) cytoplasm (Ppig)

Anatomy Link Frequency liver 3 lymph node 2 urinary bladder 1 1A2 1 lymphocytes 1 Ppig (Mus musculus)

Pain Link Frequency Relevance Heat Inflammatory stimuli 11 99.84 cytokine 120 99.70 Inflammation 281 99.50 interstitial cystitis 328 98.48 Paracetamol 37 97.84 chemokine 96 95.72 agonist 37 94.48 Cannabinoid 3 93.64 Bioavailability 5 91.00 Pain 2 90.40

Disease Link Frequency Relevance Heat INFLAMMATION 278 99.84 Cystitis 560 99.64 Malaria 180 99.60 Infection 294 98.80 Interstitial Cystitis 328 98.48 Nicotine Addiction 204 96.52 Hepatotoxicity 18 96.40 Disease 182 95.84 Stress 119 93.00 Inflammatory Bowel Disease 120 91.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In addition, the effects of AF were examined on cytochrome P450 (CYP) 2E1, the major isozyme involved in APAP bioactivation.

Spec (examined) Gene_expression (examined) of CYP

1) Confidence 0.65 Published 2009 Journal J Med Food Section Abstract Doc Link 19459732 Disease Relevance 0.25 Pain Relevance 0.15

The expression of interferon-gamma (IFN-gamma) in serum and alpha-and mu-class of gluthathione-S-transferase (GSTs), CYP 2E1 class of cytochrome monooxygenase and glutathione (GSH) in liver were quantified.

Gene_expression (expression) of CYP in liver

2) Confidence 0.58 Published 2008 Journal Chem. Biol. Interact. Section Abstract Doc Link 18237725 Disease Relevance 0.34 Pain Relevance 0.43

To this end, hepatic activities of aminolevulinic acid synthase (ALAS), heme oxygenase (HO) and CYP levels were determined in mice treated with CP-55,940 (0.5 mg/kg/day; i.p.; 5 or 24 days).

Gene_expression (levels) of CYP

3) Confidence 0.44 Published 2005 Journal Int. J. Biochem. Cell Biol. Section Abstract Doc Link 15896668 Disease Relevance 0.17 Pain Relevance 0.45

Expression of cytochrome P450 (CYP) isozymes was determined using antibodies of 2E1 and 1A2 as probes.

Spec (determined) Gene_expression (Expression) of CYP in 1A2

4) Confidence 0.39 Published 2006 Journal Basic Clin. Pharmacol. Toxicol. Section Abstract Doc Link 16445600 Disease Relevance 0.07 Pain Relevance 1.20

Metabolism by CYP and GSH conjugation are common metabolic pathways for many drugs such as APAP.

Gene_expression (conjugation) of CYP associated with paracetamol

5) Confidence 0.38 Published 2009 Journal Yakugaku Zasshi Section Abstract Doc Link 19881208 Disease Relevance 0.22 Pain Relevance 0.48

GR and LXR were significantly up-regulated in BAL cells, but no clear correlation between CYP mono-oxygenases and nuclear receptor gene expression was observed.

Gene_expression (expression) of CYP

6) Confidence 0.21 Published 2006 Journal Environ Health Perspect Section Body Doc Link PMC1665420 Disease Relevance 0.67 Pain Relevance 0

Likewise, changes in the expression of CYP transcripts may influence an individual’s capacity to convert different precarcinogenic compounds into their ultimate carcinogens; therefore, these CYP transcripts are of major importance for an individual’s susceptibility of developing chemically induced cancer.

Gene_expression (expression) of CYP associated with cancer

7) Confidence 0.18 Published 2006 Journal Environ Health Perspect Section Body Doc Link PMC1665420 Disease Relevance 0.60 Pain Relevance 0

Serum CXCL9, CXCL10, and CXCL11 levels of CYP-treated mice given control Ab were compared to similar mice that received anti-CXCL10 Ab.

Gene_expression (levels) of CYP

8) Confidence 0.18 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 1.30 Pain Relevance 0.42

This shift in the expression of the CYP epoxygenase gene might alter production of epoxy fatty acids, some of which are considered to be signalling molecules affecting vascular- and smooth muscle cell tone.

Gene_expression (expression) of CYP epoxygenase gene in smooth muscle cell

9) Confidence 0.16 Published 2006 Journal Environ Health Perspect Section Body Doc Link PMC1665420 Disease Relevance 0.64 Pain Relevance 0

Urinary bladder histology as well as mucosal (iliac lymph node and urinary bladder) and peripheral (spleen) leukocyte expression of CXCR3, CXCL9, CXCL10, and CXCL11 mRNA transcripts as well as CD4+ T cell, mast cell, and NK/NKT cell numbers were compared among naïve and CYP-treated mice given control or anti-CXCL10 Abs.

Gene_expression (expression) of CYP in T cell

10) Confidence 0.15 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 1.33 Pain Relevance 0.41

In general, the distribution of CD3+CD8+, DX-5+, and CD11b+ lymphocytes changed little after CYP-induced cystitis.

Neg (little) Gene_expression (changed) of CYP in lymphocytes associated with cystitis

11) Confidence 0.15 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 0.56 Pain Relevance 0.10

Due to the high levels of CXCL10 observed during CYP-induced cystitis, we next treated mice with control or anti-CXCL10 Abs to determine if inhibition of this chemokine would modulate disease.

Gene_expression (observed) of CYP associated with chemokine, cystitis and disease

12) Confidence 0.15 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 0.88 Pain Relevance 0.28

These clinical trends were consistent with CYP-induced cystitis in mice; CXCR3 ligands were elevated in mouse serum as well as urinary bladder and iliac lymph node lymphocytes.

Gene_expression (consistent) of CYP in lymph node associated with cystitis

13) Confidence 0.15 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 1.20 Pain Relevance 0.41

In the present study, we noticed significant increases in mast cell numbers in the spleen, iliac lymph nodes, and urinary bladder after CYP induction and these increases were abrogated by anti-CXCL10 Ab treatment.

Gene_expression (induction) of CYP in lymph nodes

14) Confidence 0.15 Published 2008 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC2583981 Disease Relevance 1.08 Pain Relevance 0.55

The mechanism by which malaria down-modulates the expression and activity of other CYP isoforms is still unclear.

Gene_expression (expression) of CYP associated with malaria

15) Confidence 0.10 Published 2010 Journal Malar J Section Body Doc Link PMC2858213 Disease Relevance 0.98 Pain Relevance 0.15

The idea that NO is a mediator of the down-modulation of CYP expression by inflammatory stimuli is plausible because NO binds haem proteins and inhibits catalytic activities of CYPs in in vitro test systems [16,17].

Gene_expression (expression) of CYP associated with inflammatory stimuli

16) Confidence 0.10 Published 2010 Journal Malar J Section Body Doc Link PMC2858213 Disease Relevance 0.57 Pain Relevance 0.13

Thus, information about the expression of CYP families and subfamilies should be valuable from two viewpoints.

Gene_expression (expression) of CYP

17) Confidence 0.09 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0 Pain Relevance 0

Of note, CYP3A4 is the most abundantly expressed CYP in h-liver and metabolizes >60% of all therapeutic drugs; collectively, CYP2D6 and CYP3A4 metabolize >70% of the drugs on the market [17].

Gene_expression (expressed) of CYP in liver

18) Confidence 0.09 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0 Pain Relevance 0

Second, the h-CYP-expressing chimeric mouse is a useful experimental model for studying h-type metabolic responses to xenobiotics, including clinically valuable drugs.

Gene_expression (expressing) of CYP

19) Confidence 0.09 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0 Pain Relevance 0

Thus, the h-hepatocytes in the chimeric mice appeared to express the six h-CYP genes in a manner similar to their expression in the h-body.

Gene_expression (express) of CYP in body

20) Confidence 0.07 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0 Pain Relevance 0

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