INT121242

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Context Info
Confidence 0.69
First Reported 2003
Last Reported 2010
Negated 4
Speculated 1
Reported most in Body
Documents 37
Total Number 45
Disease Relevance 31.96
Pain Relevance 12.71

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mitochondrion (Nos3) Golgi apparatus (Nos3) cytoplasm (Nos3)
signal transduction (Nos3) oxidoreductase activity (Nos3) nucleolus (Nos3)
Anatomy Link Frequency
sciatic nerve 10
spinal cord 6
neuronal 4
blood 4
peritoneum 2
Nos3 (Mus musculus)
Pain Link Frequency Relevance Heat
Spinal cord 521 100.00 Very High Very High Very High
Neuronal nitric oxide synthase 5 100.00 Very High Very High Very High
Neuropathic pain 218 99.84 Very High Very High Very High
Sciatic nerve 696 99.74 Very High Very High Very High
ischemia 24 99.52 Very High Very High Very High
Inflammation 168 98.98 Very High Very High Very High
dorsal root ganglion 46 98.72 Very High Very High Very High
Bioavailability 16 97.72 Very High Very High Very High
IPN 43 97.60 Very High Very High Very High
Dorsal horn 14 97.36 Very High Very High Very High
Disease Link Frequency Relevance Heat
Targeted Disruption 1021 100.00 Very High Very High Very High
Disorder Of Lipid Metabolism 417 99.98 Very High Very High Very High
Nervous System Injury 361 99.88 Very High Very High Very High
Neuropathic Pain 521 99.84 Very High Very High Very High
Stress 143 99.66 Very High Very High Very High
Cv Unclassified Under Development 20 99.52 Very High Very High Very High
Disease 378 99.40 Very High Very High Very High
INFLAMMATION 217 98.98 Very High Very High Very High
Coronary Heart Disease 22 98.76 Very High Very High Very High
Hypertension 339 98.52 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and endothelial function involves increased expression of endothelial nitric oxide synthase (eNOS).
Positive_regulation (increased) of Gene_expression (expression) of eNOS
1) Confidence 0.69 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.55 Pain Relevance 0.14
Meanwhile, Western blot showed that eNOS expression in the spinal cord of nNOS knockout mice was up-regulated compared with wild-type mice; immunohistochemical staining showed that the spinal eNOS was mainly distributed in superficial laminae of the dorsal horn.
Positive_regulation (up-regulated) of Gene_expression (expression) of eNOS in dorsal horn associated with targeted disruption, dorsal horn and spinal cord
2) Confidence 0.65 Published 2004 Journal Neuroscience Section Abstract Doc Link 15350652 Disease Relevance 0.99 Pain Relevance 0.65
Furthermore, in a mouse model of hindlimb ischemia, repeated Waon therapy increased eNOS protein expression, blood flow, and capillary density.
Positive_regulation (increased) of Gene_expression (expression) of eNOS in blood associated with ischemia
3) Confidence 0.61 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.63 Pain Relevance 0.15
Our data also indicate that the enhanced spinal cord expression of NOS3 in NOS1-KO mice might compensates for the lack of NOS1 under basal conditions but not after sciatic nerve ligation.
Positive_regulation (enhanced) of Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption, sciatic nerve and spinal cord
4) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.49 Pain Relevance 0.92
Sciatic nerve injury also increases the spinal cord expression of NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively.
Positive_regulation (increases) of Gene_expression (expression) of NOS3 in NOS1 associated with targeted disruption, nervous system injury, sciatic nerve and spinal cord
5) Confidence 0.60 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3001461 Disease Relevance 1.79 Pain Relevance 1.07
However, while the disruption of NOS1 gene did not alter the mRNA or protein levels of NOS2 in sham-operated mice a significant increase in the spinal cord expression of NOS3 was further demonstrated in sham-operated NOS1-KO mice [18].
Positive_regulation (increase) of Gene_expression (expression) of NOS3 in spinal cord associated with targeted disruption and spinal cord
6) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.15 Pain Relevance 0.85
Densitometry analysis confirmed that LPS treatment induced an 11-fold increase in nNOS expression (relative optical density: 1170 ± 200%, P = 0.005), and 2-fold increase in eNOS expression (relative optical density: 247 ± 110%, P = 0.01) in the peritoneum (Figure 4B).


Positive_regulation (increase) of Gene_expression (expression) of eNOS in peritoneum
7) Confidence 0.57 Published 2010 Journal Nephrology Dialysis Transplantation Section Body Doc Link PMC2796899 Disease Relevance 0.47 Pain Relevance 0.03
Estrogen increases the expression and activity of eNOS [19], [20].
Positive_regulation (increases) of Gene_expression (expression) of eNOS
8) Confidence 0.56 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2982841 Disease Relevance 0 Pain Relevance 0
Female animals produce more estrogen which is known to enhance the vascular expression and activity of eNOS [22], [25].
Positive_regulation (enhance) of Gene_expression (expression) of eNOS
9) Confidence 0.56 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2982841 Disease Relevance 0.60 Pain Relevance 0
It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and endothelial function involves increased expression of endothelial nitric oxide synthase (eNOS).
Positive_regulation (increased) of Gene_expression (expression) of endothelial nitric oxide synthase
10) Confidence 0.50 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.55 Pain Relevance 0.14
The impaired functional activity of bone marrow cells from patients could be partially restored after pharmacological enhancement of eNOS expression or nitric oxide donors, which highlights the important role of endothelium-derived NO for neovascularization [15], [16].
Positive_regulation (enhancement) of Gene_expression (expression) of eNOS in endothelium
11) Confidence 0.45 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2654072 Disease Relevance 0.53 Pain Relevance 0.04
Our results revealed that the mRNA expression of inducible nitric oxide synthase (iNOS) was reduced by approximately 50% in GEB-pretreated mice versus the controls, whereas the mRNA expression levels of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) remained unchanged.
Neg (unchanged) Positive_regulation (unchanged) of Gene_expression (expression) of endothelial nitric oxide synthase in neuronal associated with neuronal nitric oxide synthase
12) Confidence 0.45 Published 2007 Journal Int. J. Mol. Med. Section Abstract Doc Link 17611639 Disease Relevance 0.46 Pain Relevance 0.14
In contrast, neuronal NO synthase (nNos) expression was reduced in both soleus and white vastus lateralis muscles (Fig. 2D), whereas endothelial NO synthase (eNos) expression was low in white vastus lateralis muscles under basal conditions and was induced to a level comparable to that in the soleus muscles (Fig. 2E) following LPS injection.
Positive_regulation (induced) of in muscles Gene_expression (expression) of eNos in vastus lateralis
13) Confidence 0.44 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2361191 Disease Relevance 0.25 Pain Relevance 0
The two way ANOVA showed a significant effect of the genotype (p<0.015) and surgery (p<0.034) and according to what occurs with the mRNA expression, while the NOS3 expression in sham-operated NOS1-KO mice was significantly higher to than those observed in sham-operated WT or NOS2-KO mice (one way ANOVA, p<0.006), these differences between genotypes disappear after sciatic nerve ligation.


Positive_regulation (operated) of Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption and sciatic nerve
14) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.16 Pain Relevance 0.60
Our data also indicate that the enhanced spinal cord expression of NOS3 in NOS1-KO mice might compensates for the lack of NOS1 under basal conditions but not after sciatic nerve ligation.
Neg (not) Spec (might) Positive_regulation (compensates) of Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption, sciatic nerve and spinal cord
15) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.51 Pain Relevance 0.92
Indeed, our results showed that while the spinal cord expression of NOS3 in sham-operated NOS1-KO mice was significantly higher than those presented in WT and NOS2-KO mice (one way ANOVA, p<0.005), non significant differences between genotypes were found at 21 days after nerve injury.
Positive_regulation (operated) of Gene_expression (expression) of NOS3 in spinal cord associated with targeted disruption, nervous system injury and spinal cord
16) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.17 Pain Relevance 0.49
The possible alterations in NOS2 and NOS3 expression induced by neuropathic pain have been also evaluated in this study.
Positive_regulation (induced) of Gene_expression (expression) of NOS3 associated with neuropathic pain
17) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 0.86 Pain Relevance 0.75
Several works have demonstrated that nerve injury after sciatic nerve ligation evoked an increased NOS1 and NOS2, but not of NOS3, protein expression in the ipsilateral site of the dorsal root ganglia and the sciatic nerve [4], [6]–[11].
Neg (not) Positive_regulation (increased) of Gene_expression (expression) of NOS3 in sciatic nerve associated with nervous system injury and sciatic nerve
18) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.55 Pain Relevance 1.22
Theoretically, increased eNOS levels produce an increase in S-nitrosylated proteins.
Positive_regulation (increase) of Gene_expression (produce) of eNOS
19) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2982841 Disease Relevance 0.45 Pain Relevance 0
However, the possible changes in the expression of NOS1, NOS2 and NOS3 isoforms that might occurs in the spinal cord of NOS1 and NOS2 knockout mice after total sciatic nerve ligation remains unknown.
Positive_regulation (occurs) of Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption, sciatic nerve and spinal cord
20) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.03 Pain Relevance 0.94

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