INT243689

Context Info Confidence 0.35 First Reported 2008 Last Reported 2009 Negated 0 Speculated 1 Reported most in Body Documents 1 Total Number 5 Disease Relevance 2.72 Pain Relevance 1.97

nucleoplasm (NFKB2) extracellular matrix organization (NFKB2) DNA binding (NFKB2) cytoplasm (NFKB2) cytosol (NFKB2) signal transduction (NFKB2)

Anatomy Link Frequency macrophages 1 NFKB2 (Homo sapiens)

Pain Link Frequency Relevance Heat corticosteroid 224 99.70 Inflammatory response 228 97.60 Inflammation 378 97.24 Inflammatory stimuli 140 95.08 Inflammatory mediators 16 95.04 aspirin 48 86.64 cytokine 63 84.16 dexamethasone 5 63.44 tolerance 4 37.40 cINOD 14 19.96

Disease Link Frequency Relevance Heat INFLAMMATION 647 97.24 Disease 26 95.76 Disease Progression 4 71.04 Necrosis 2 42.72 Stress 4 9.08 Systemic Inflammatory Response Syndrome 16 5.00 Injury 13 5.00 Targeted Disruption 8 5.00 Arthritis 6 5.00 Critical Illness 4 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

However, sensitivity analysis [55] demonstrated that the activity of NFkB is maximally modulated by a reduced set of basis signaling molecules (IKK, IKBa and NFkB).

Regulation (modulated) of NFkB

1) Confidence 0.35 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.48 Pain Relevance 0.24

If we assume that corticosteroids instead of up-regulating the inhibitor of NFkB they prime the production rate of IL10 signaling (A), Figure 12 is extended to Figure 13.

Regulation (regulating) of NFkB associated with corticosteroid

2) Confidence 0.26 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.71 Pain Relevance 0.62

As such, we will explore means of modulating the activity of NFkB through the use of corticosteroids Developing mechanistic models of inflammation allows us to both characterize the non-linear inflammatory trajectory under various “what-if” scenarios and importantly to evaluate the effectiveness of drug-based treatment strategies that modulate the dynamics of the system.

Regulation (modulating) of NFkB associated with corticosteroid and inflammation

3) Confidence 0.16 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.70 Pain Relevance 0.35

However, at t>3 hr the activity of NFkB cannot be regulated successfully and it settles to a sustained elevated state that drives downstream the over-excitation of both pro- and anti-inflammatory mediators; leading to an unconstrained inflammatory response.

Regulation (regulated) of NFkB associated with inflammatory response and inflammatory mediators

4) Confidence 0.16 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.65 Pain Relevance 0.40

release from lipopolysaccharide (LPS)-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-?

Spec (investigate) Regulation (effects) of nuclear factor-kappa B in macrophages

5) Confidence 0.07 Published 2008 Journal J Inflamm (Lond) Section Abstract Doc Link PMC2525633 Disease Relevance 0.18 Pain Relevance 0.36

General Comments

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