Entries by tag: immunology
EPIGENETICS OF DM2: GLUCOCORTICOID AND VIT D RECEPTORS MEDIATE
ALSO TNF ALPHA OR DEXAMETHASONE INDUCES IR
http://www.nature.com/ncb/journal/v17/n1/full/ncb3080.html
Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis
Sona Kang, Linus T. Tsai, Yiming Zhou, Adam Evertts, Su Xu, Michael J. Griffin, Robbyn Issner, Holly J. Whitton, Benjamin A. Garcia, Charles B. Epstein, Tarjei S. Mikkelsen & Evan D. Rosen
Nature Cell Biology 17, 44–56 (2015) doi:10.1038/ncb3080
Received 06 August 2014 Accepted Nov 2014 Published online 15 Dec 2014
Abstract
Insulin resistance is a cardinal feature of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, ageing and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumour necrosis factor-α or by the steroid dexamethasone to construct detailed transcriptional and epigenomic maps associated with cellular insulin resistance. These data predict that the glucocorticoid receptor and vitamin D receptor are common mediators of insulin resistance, which we validate using gain- and loss-of-function studies. These studies define a common transcriptional and epigenomic signature in cellular insulin resistance enabling the identification of pathogenic mechanisms.
ALSO TNF ALPHA OR DEXAMETHASONE INDUCES IR
http://www.nature.com/ncb/journal/v17/n1/full/ncb3080.html
Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis
Sona Kang, Linus T. Tsai, Yiming Zhou, Adam Evertts, Su Xu, Michael J. Griffin, Robbyn Issner, Holly J. Whitton, Benjamin A. Garcia, Charles B. Epstein, Tarjei S. Mikkelsen & Evan D. Rosen
Nature Cell Biology 17, 44–56 (2015) doi:10.1038/ncb3080
Received 06 August 2014 Accepted Nov 2014 Published online 15 Dec 2014
Abstract
Insulin resistance is a cardinal feature of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, ageing and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumour necrosis factor-α or by the steroid dexamethasone to construct detailed transcriptional and epigenomic maps associated with cellular insulin resistance. These data predict that the glucocorticoid receptor and vitamin D receptor are common mediators of insulin resistance, which we validate using gain- and loss-of-function studies. These studies define a common transcriptional and epigenomic signature in cellular insulin resistance enabling the identification of pathogenic mechanisms.
Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation.
Baek SY1, Lee J1, Lee DG1, Park MK1, Lee J2, Kwok SK2, Cho ML1, Park SH2.
Abstract
AIM:
Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects.
METHODS:
CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies.
RESULTS:
UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro.
CONCLUSION:
UA treatment significantly ameliorates CIA in mice via suppression of Th17 and differentiation. By targeting pathogenic Th17 cells and autoantibody production, UA may be useful for the treatment of autoimmune arthritis and other Th17-related diseases.
PMID: 25087995 [PubMed - in process] PMCID: PMC4155530
SOURCE
http://www.ncbi.nlm.nih.gov/pubmed/25087995
Acta Pharmacol Sin. 2014 Sep;35(9):1177-87. doi: 10.1038/aps.2014.58. Epub 2014 Aug 4.
Baek SY1, Lee J1, Lee DG1, Park MK1, Lee J2, Kwok SK2, Cho ML1, Park SH2.
Abstract
AIM:
Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects.
METHODS:
CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies.
RESULTS:
UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro.
CONCLUSION:
UA treatment significantly ameliorates CIA in mice via suppression of Th17 and differentiation. By targeting pathogenic Th17 cells and autoantibody production, UA may be useful for the treatment of autoimmune arthritis and other Th17-related diseases.
PMID: 25087995 [PubMed - in process] PMCID: PMC4155530
SOURCE
http://www.ncbi.nlm.nih.gov/pubmed/25087995
Acta Pharmacol Sin. 2014 Sep;35(9):1177-87. doi: 10.1038/aps.2014.58. Epub 2014 Aug 4.
Modulation of autoimmune rheumatic diseases by oestrogen and progesterone
• Grant C. Hughes & Divaker Choubey
Nature Reviews Rheumatology 10, 740–751 (2014) doi:10.1038/nrrheum.2014.144
Published online 26 August 2014
http://www.nature.com/nrrheum/journal/v10/n12/full/nrrheum.2014.144.html
Abstract
Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4+ T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health—a newly announced directive of the NIH.
• Grant C. Hughes & Divaker Choubey
Nature Reviews Rheumatology 10, 740–751 (2014) doi:10.1038/nrrheum.2014.144
Published online 26 August 2014
http://www.nature.com/nrrheum/journal/v10/n12/full/nrrheum.2014.144.html
Abstract
Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4+ T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health—a newly announced directive of the NIH.
First time I've heard of IgD: 11/26/14. From Dr D'Adamo. =-]
QUICK REFERENCE RANDOM ASSOCIATIONS IN semi-ALPHABETICAL ORDER
( This list is brought forward and updated with new information.Collapse )
QUICK REFERENCE RANDOM ASSOCIATIONS IN semi-ALPHABETICAL ORDER
( This list is brought forward and updated with new information.Collapse )
- Current Mood:
amused
Designs for Health Research & Education Blog
Breathe Easier with Bromelain
Posted on Thu, Oct 09, 2014 @ 09:30 AM
Here: http://info.designsforhealth.com/blog/breathe-easier-with-bromelain accessed 10/10/14
( NotesCollapse )
Breathe Easier with Bromelain
Posted on Thu, Oct 09, 2014 @ 09:30 AM
Here: http://info.designsforhealth.com/blog/breathe-easier-with-bromelain accessed 10/10/14
( NotesCollapse )
Just ran across a nice southern article about eating the leaves as salad, and painting the skin with the toxic berry juice. I have been taught to use an alcohol extract of the root as a "lymphogogue" meaning it is supposed to stimulate lymph movement, or at least a strong immune response. Far as I know there is no science to support this use. The juices of the root are very strong and caustic, and it should not be handled with bare hands.
The National Institutes of Health, 10 large drug companies and seven nonprofit organizations announced an unconventional partnership on Tuesday intended to speed up development of drugs to treat Alzheimer’s disease, Type 2 diabetes, rheumatoid arthritis and lupus.
During the course of a five-year, $230 million effort, the participants will share data in regular conference calls and meetings, working together to determine which findings are likely to lead to effective treatments. They will make their findings and data publicly available.
...What concerns me about this is the emphasis on drugs. There are better ways to adjust physiology than taking in foreign substances. And there are more useful things we could study. Like food, and exercise, and how to they affect our biochemical and electrical mileau. Sex, we should throw more money at studying sex and how it affects neurotransmitters. On the effects of chewing gum and on understanding the endocrinology of sexual preference. And on why our hearts slow down as we age, and a million other questions. I'm just curious: I really want to know the answers. I wish that the money spent on medical research was directed more by altruism and less by profit motive.
SOURCE
http://www.nytimes.com/2014/02/05/health/nih-joins-drug-makers-and-nonprofits-on-stubborn-diseases.html
During the course of a five-year, $230 million effort, the participants will share data in regular conference calls and meetings, working together to determine which findings are likely to lead to effective treatments. They will make their findings and data publicly available.
...What concerns me about this is the emphasis on drugs. There are better ways to adjust physiology than taking in foreign substances. And there are more useful things we could study. Like food, and exercise, and how to they affect our biochemical and electrical mileau. Sex, we should throw more money at studying sex and how it affects neurotransmitters. On the effects of chewing gum and on understanding the endocrinology of sexual preference. And on why our hearts slow down as we age, and a million other questions. I'm just curious: I really want to know the answers. I wish that the money spent on medical research was directed more by altruism and less by profit motive.
SOURCE
http://www.nytimes.com/2014/02/05/health/nih-joins-drug-makers-and-nonprofits-on-stubborn-diseases.html
In the field, some practitioners will pack an open wound with black soil to help it heal. You can get black peat that is used for this purpose and others. It is not pasteurized or sterilized in any way; it is full of living organisms. After the battle of Shiloh in the US civil war, soldiers whose wounds glowed in the dark had better survival. The organism (Photorhabdus luminescens) that was growing in their wounds came from the guts of nematodes living in the soil. Presumably this organism outcompeted the pathogenic ones. This kind of antibiotic mechanism cannot be ignored when antibiotic drugs are increasing ineffective.
( More about the biology, and the source, behind cut.Collapse )
( More about the biology, and the source, behind cut.Collapse )
The Russians have known about phages and used them to treat severe infections since the 1930's. New research shows that lots of phages live in mucus. Wherever there is mucus there is likely to be a large population of phages--including mucus produced by other species such as sea coral, plants, etc.
Phages are viruses that use bacterial cells to replicate in. They can also insert new DNA into bacteria, and they are able to evolve quickly enough to keep up with changing resistance patterns. Big Pharma is not putting any money toward phage research because phage therapy would compete with antibiotic sales, and as we know, for them, the bottom line IS the bottom line. They want us to think that phages are dangerous. But according to Dr Mercola a normal human produces approximately a quart of mucus (snot) daily in the upper respiratory tract, most of which we swallow. So we are phage central already.
( notes from Mercola's new article on phagesCollapse )
Phages are viruses that use bacterial cells to replicate in. They can also insert new DNA into bacteria, and they are able to evolve quickly enough to keep up with changing resistance patterns. Big Pharma is not putting any money toward phage research because phage therapy would compete with antibiotic sales, and as we know, for them, the bottom line IS the bottom line. They want us to think that phages are dangerous. But according to Dr Mercola a normal human produces approximately a quart of mucus (snot) daily in the upper respiratory tract, most of which we swallow. So we are phage central already.
( notes from Mercola's new article on phagesCollapse )
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