INT165530

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Context Info
Confidence 0.69
First Reported 2010
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 4
Total Number 18
Disease Relevance 1.21
Pain Relevance 1.05

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

anatomical structure formation involved in morphogenesis (Shh) Golgi apparatus (Shh) endoplasmic reticulum (Shh)
embryo development (Shh) cell-cell signaling (Shh) signal transducer activity (Shh)
Anatomy Link Frequency
tube 1
blood vessels 1
heart 1
Shh (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Chronic pancreatitis 9 99.48 Very High Very High Very High
cytokine 45 97.64 Very High Very High Very High
Inflammation 15 97.60 Very High Very High Very High
fibrosis 15 93.60 High High
Neuronal nitric oxide synthase 15 87.60 High High
anesthesia 15 79.88 Quite High
Central nervous system 15 70.32 Quite High
metalloproteinase 15 40.12 Quite Low
ischemia 15 5.00 Very Low Very Low Very Low
Inflammatory response 15 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Pancreatitis 9 99.48 Very High Very High Very High
INFLAMMATION 30 97.60 Very High Very High Very High
Fibrosis 15 93.60 High High
Increased Venous Pressure Under Development 15 84.56 Quite High
Myocardial Infarction 90 82.88 Quite High
Apoptosis 15 42.96 Quite Low
Infarction 60 39.56 Quite Low
Injury 30 12.32 Low Low
Hemangioma 15 5.00 Very Low Very Low Very Low
Death 15 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
OBJECTIVE: To establish a rat model of chronic pancreatitis, and to prove the activation of sonic hedgehog (SHH) signaling pathways in chronic pancreatitis.
Positive_regulation (activation) of SHH associated with chronic pancreatitis
1) Confidence 0.69 Published 2010 Journal Saudi Med J Section Abstract Doc Link 20062892 Disease Relevance 0.27 Pain Relevance 0.27
OBJECTIVE: To establish a rat model of chronic pancreatitis, and to prove the activation of sonic hedgehog (SHH) signaling pathways in chronic pancreatitis.
Positive_regulation (activation) of sonic hedgehog associated with chronic pancreatitis
2) Confidence 0.69 Published 2010 Journal Saudi Med J Section Abstract Doc Link 20062892 Disease Relevance 0.27 Pain Relevance 0.27
iNOS gene expression was significantly increased in ShhMSCs as compared to EmpMSCs (Figure 3A) which was confirmed by Western blot (Figure 3B).
Positive_regulation (increased) of ShhMSCs
3) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
We further observed that PKM was upregulated in ShhMSCs and was sensitive to cyclopamine and chel pretreatment of the cells.


Positive_regulation (upregulated) of ShhMSCs
4) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
The salient findings of the study are: 1- Genetic modification of MSCs with Shh transgene results in multifold increased iNOS upregulation and NO production, an effect which was associated with higher level of angiogenic growth factor expression including VEGF, Ang-1 and netrin-1. 2- The induction of iNOS in ShhMSCs occurred in PKC dependent manner. 3- ShhCM mediated increased angiogenic response was abrogated in the presence of Shh and netrin-1 specific antibodies. 4- Intramyocardial engraftment of ShhMSC induced significant angiogenesis, improved regional blood flow and significantly preserved global heart function.
Positive_regulation (induction) of ShhMSCs in heart
5) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.08 Pain Relevance 0
Our results showed that netrin-1 expression increased significantly in ShhMSCs both at the protein and RNA levels in PKC (PKM) dependent fashion.
Positive_regulation (increased) of ShhMSCs
6) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.08 Pain Relevance 0.04
The SHH signaling pathway is activated in rats with chronic pancreatitis.


Positive_regulation (activated) of SHH
7) Confidence 0.50 Published 2010 Journal Saudi Med J Section Body Doc Link 20062892 Disease Relevance 0.05 Pain Relevance 0
In vitro angiogenic response of HUVECs to ShhCM was determined by tube formation assay on matrigel which showed that morphological changes were most obvious at 6-h after incubation of the cells with ShhCM as compared with conditioned medium from empty vector transfected MSCs (EmpCM) (Figure 2C).
Positive_regulation (response) of ShhCM in tube
8) Confidence 0.48 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
In our present study, treatment of ShhMSCs with both the PKC inhibitor chel and Shh inhibitor cyclopamine abolished PKM fragment which indicated that PKM was downstream of Shh and that PKC was essential for its upregulation.
Positive_regulation (treatment) of Shh
9) Confidence 0.48 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.06 Pain Relevance 0
Fluorescent immunostaining showed that more than 65% cells stained positive for Shh transgene overexpression (Figure 1C).
Positive_regulation (positive) of Shh transgene
10) Confidence 0.45 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0.08
Activation of Shh pathway upregulates the expression of multiple angiogenic cytokines, including VEGF, angiopoietins, SDF-1?
Positive_regulation (Activation) of Shh associated with cytokine
11) Confidence 0.45 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.09 Pain Relevance 0.13
In our present study, treatment of ShhMSCs with both the PKC inhibitor chel and Shh inhibitor cyclopamine abolished PKM fragment which indicated that PKM was downstream of Shh and that PKC was essential for its upregulation.
Positive_regulation (treatment) of ShhMSCs
12) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.06 Pain Relevance 0
The cytoprotective effects were accompanied by a significant increase in capillary density and a higher number of mature blood vessels (smooth muscle actin positive cells) in ShhMSCs group.
Positive_regulation (increase) of ShhMSCs in blood vessels
13) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0.04
We also found that Shh overexpression also induced panPKC fragment PKM (45 kd; a proteolytic subunit of PKC) in ShhMSCs which was completely abolished by pretreatment of the cells with 2.5 µM chel or 1 µM cyclopamine (Figure 3E).
Positive_regulation (induced) of ShhMSCs
14) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
Pretreatment of ShhMSCs with these inhibitors abrogated PKM with concurrent abrogation of iNOS and netrin-1.
Positive_regulation (Pretreatment) of ShhMSCs
15) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
Measurement of NO activity by using a colorimetric NO assay kit showed that Shh overexpression was associated with a concomitant increase in NO production in ShhMSCs (Figure 3C).
Positive_regulation (increase) of ShhMSCs
16) Confidence 0.39 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0 Pain Relevance 0
Put together, these molecular changes lead to a significant increase in biologically active NO production in ShhMSCs.
Positive_regulation (increase) of ShhMSCs
17) Confidence 0.39 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.17 Pain Relevance 0.21
The results from the present study also indicated that genetically engineered ShhMSCs promoted migration of endothelial progenitor cells which may be attributed to the dramatic upregulation of MMP-9 (4-fold) in ShhMSCs.
Positive_regulation (upregulation) of ShhMSCs
18) Confidence 0.39 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2797399 Disease Relevance 0.06 Pain Relevance 0

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