INT184665

Context Info Confidence 0.28 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 7 Total Number 9 Disease Relevance 5.84 Pain Relevance 0.90

extracellular space (C4b) extracellular region (C4b)

Anatomy Link Frequency NFAT 3 neocortex 1 nucleus 1 hippocampus 1 cerebellum 1 C4b (Mus musculus)

Pain Link Frequency Relevance Heat Hippocampus 144 99.96 cva 8 99.22 addiction 1 81.08 unmyelinated 6 80.16 Inflammation 49 64.88 nav1.8 3 64.88 c fibre 3 64.32 Central nervous system 18 53.48 Peripheral nervous system 6 49.56 Demyelination 18 46.88

Disease Link Frequency Relevance Heat Aging 403 99.68 Colon Cancer 1 99.48 Cv General 3 Under Development 8 99.22 Myocardial Infarction 49 97.98 Acute Coronary Syndrome 3 96.68 Cancer 63 96.00 Sprains And Strains 372 94.64 Prostate Cancer 34 87.72 Obesity 2 83.24 Apoptosis 61 78.40

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

C4 was also upregulated in the aging neocortex and cerebellum of B6J, suggesting that the complement cascade plays a common role in aging in multiple inbred mouse strains and brain regions [47].

Positive_regulation (upregulated) of C4 in neocortex associated with aging and sprains and strains

1) Confidence 0.28 Published 2005 Journal Genome Biol Section Body Doc Link PMC1175968 Disease Relevance 0.83 Pain Relevance 0.12

In the hippocampus, C4 was upregulated in old S8, S10, SR1 and B6J mice.

Positive_regulation (upregulated) of C4 in hippocampus associated with hippocampus

2) Confidence 0.28 Published 2005 Journal Genome Biol Section Body Doc Link PMC1175968 Disease Relevance 0.82 Pain Relevance 0.12

Lack of calcineurin B prevents neuregulin-induced dephosphorylation and activation of NFAT c3 and c4.

Positive_regulation (activation) of c4 in NFAT

3) Confidence 0.13 Published 2010 Journal F1000 Biol Rep Section Body Doc Link PMC2948355 Disease Relevance 0 Pain Relevance 0.03

Furthermore, NFAT c4 complexes with Sox-10, a transcription factor required for myelination [17], to activate the promoter and myelin-specific enhancer of the Krox-20 gene, which globally regulates peripheral myelination [11,18-20], and also with the promoter of the myelin protein zero (P0) gene, all of which underline the involvement of NFAT proteins in myelination.

Positive_regulation (activate) of c4 in NFAT

4) Confidence 0.11 Published 2010 Journal F1000 Biol Rep Section Body Doc Link PMC2948355 Disease Relevance 0 Pain Relevance 0.03

C4 was also upregulated in the aging neocortex and cerebellum of B6J, suggesting that the complement cascade plays a common role in aging in multiple inbred mouse strains and brain regions [47].

Positive_regulation (upregulated) of C4 in cerebellum associated with aging and sprains and strains

5) Confidence 0.10 Published 2005 Journal Genome Biol Section Body Doc Link PMC1175968 Disease Relevance 0.83 Pain Relevance 0.12

Moreover, immune parameters specifically related to the age of colorectal cancer patients, such as higher levels of C3, C4 and immunosuppressive acidic protein (IAP), and lower T cell stimulation index could contribute to cancer development and explain why they respond to a lesser extent to adjuvant immunochemotherapy than immunologically intact young subjects (Munemoto et al 2004).

Positive_regulation (levels) of C4 in T cell associated with cancer and colon cancer

6) Confidence 0.09 Published 2007 Journal Clinical Interventions in Aging Section Body Doc Link PMC2684090 Disease Relevance 1.11 Pain Relevance 0.03

Finally, C3 and C4 levels in patients admitted for AMI were significantly higher than in patients with stable angina or healthy controls, and the serum C3/C4 ratio could possibly be used as a marker of subsequent cardiovascular events after a previous manifestation of ACS (Iltumur et al 2005; Palikhe et al 2007).

Positive_regulation (used) of C4 associated with acute coronary syndrome, cva and myocardial infarction

7) Confidence 0.07 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727911 Disease Relevance 1.54 Pain Relevance 0.17

This activates the phosphatase calcineurin, which dephosphorylates nuclear factor of activated T cells (NFAT) c3 and c4, resulting in translocation to the nucleus.

Positive_regulation (activated) of c4 in nucleus

8) Confidence 0.06 Published 2010 Journal F1000 Biol Rep Section Body Doc Link PMC2948355 Disease Relevance 0 Pain Relevance 0.23

C4-2BADLuc cells were generated by transfecting C4-2 cells with wild-type BAD (HA-BAD-pTRE2hygro) and firefly luciferase (PGL3) whereas pTRE2hygro and firefly luciferase (PGL3) were transfected into C4-2 cells to generate C4-2Luc.

Positive_regulation (generate) of C4-2Luc

9) Confidence 0.01 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2704953 Disease Relevance 0.72 Pain Relevance 0.04

General Comments

This test has worked.