Anti-Inflammatory Diet

Anti-Inflammatory Diet and Lifestyle.
more articles by Prof. Ayers on Suite101 .

Thursday, April 30, 2009

Extreme Flu Remedies

Experimental Therapies for ARDS, Cytokine Storms



Cytokine Storms Are Out of Control




Silence the Storms


HSPGs Mediate Cytokine Signaling

Heparin Can Block Cytokine Signaling


Berberine Binds to HSPG

Curcumin Blocks NFkB

Anti-Inflammatory Diet

Monday, April 27, 2009

Inflammatory Protection from Swine Flu

Inflammation causes allergies, autoimmune and degenerative diseases, and is the foundation for cancer, but it does provide protection against infection.

One of the reasons that older people are less prone to infectious diseases, is that their immune systems have already been exposed to earlier versions of pathogens. Another reason for the relative good health of the parents of baby boomers, is that chronic inflammation increases with age and protection against pathogens is the adaptive advantage of inflammation.

As of now, the new swine flu pre-epidemic is very scary in Mexico City, but doesn’t pack much of a punch north of the border. Maybe it is too early to be optimistic, but it is tantalizing to speculate that the diet-based chronic inflammation that stuffs the coffins in the US, may be good for something besides stuffing the coffers of agribusiness.

One of the symptoms of high chronic inflammation is many years without a day of sick leave. It is hard for a pathogen to get a foothold when the immune system is already provoked by inflammation. Even food and harmless pollen is attacked with vigor and lots of sneezing.

Swine flu is attacking the young and healthy in Mexico. King Corn has already wiped out those targets in the US. Obesity fed by starch, vegetable oils and corn-fed meat, produces chronic inflammation and a potential resistance to swine flu. The US diet provides the inflammatory benefits of old age for the young.

This explains why I live in Idaho. Here it is easy to maintain an island of health in a sea of inflammation. Few visitors with infectious diseases can travel from healthy countries fast enough to transmit the diseases before they show symptoms. Everyone else who reads my advice, lowers their inflammation and lives longer, healthier lives free of chronic diseases, had better start washing their hands and wearing face masks.

Friday, April 24, 2009

Stem Cells Using HSPG Uptake of Recombinant Transcription Factors

Stem Cells from Adult Cells using Transcription Factor Genes
Stem cells have been produced from adult cells using transformation with genes for transcription factors. The problem with this approach was that the embryonic transcription factors had a tendency to promote cancer-like proliferation. What was needed was a temporary push toward embryonic gene expression by temporarily introducing a dose of embryonic transcription factors to dominate gene expression long enough to convert adult, differentiated cells into pluripotent stem cells.

Transcription Factors Synthesized by Recombinant Bacteria
The technical solution was tested and successful results were announced in a prior to publication paper in the journal Cell Stem Cell. Four transcription factors successfully used in prior experiments to induce stem cell transformation were synthesized using recombinant bacteria. The problem was getting the proteins into skin cells that were already growing in cell culture.

Protein Uptake via Triplets of Basic Amino Acids (Heparin-Binding Domains, NLS)
Transcription factors bind to DNA via basic amino acids and many of those basic amino acids are parts of the nuclear localization signals (NLS, quartet or two neighboring pairs of basic amino acids) that bind to importin and transport transcription factors from the cytoplasm to the nucleus.

HSPG Circulation Should Take in Transcription Factors
By inspection, I have demonstrated that proteins observed to be taken up by cells, without specific receptors, e.g. HIV-TAT, lactoferrin, heparanase, allergens, autoantigens, have triplets (or neighboring pairs) or basic amino acids, and this uptake is inhibited by heparin. One would expect that transcription factors would be naturally taken into cells by HSPG circulation. Just adding recombinant transcription factors to cultured skin cells should transform them into stem cells. I don’t believe that this was tested. Instead, more powerful heparin-binding domains were added.

Poly Arginine was used for Uptake of Transcription Factors
The investigators ensured a high efficiency of uptake by adding potent poly arginine sequences to the ends of the transcription factors and synthesized them in recombinant bacteria. The recombinant, arg-tailed transcription factors were taken up by the cultured skin cells and changed the pattern of gene expression in the skin cells. The cultured cells reverted to embryonic patterns of gene expression of pluripotent stem cells. The recombinant proteins were eventually metabolized, but the stem cells had been stably transformed.

Zhou, H. et al., Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins, Cell Stem Cell (2009), ahead of publication 04.005

Thursday, April 23, 2009

Allergy, Asthma, Autoimmunity Start the Same Way

Inflammation is the current medical buzzword. Name the disease and inflammation is there.

Reproduction Requires Controlled Inflammation
Aspirin blocks many of the steps in triggering inflammation and thus, aspirin administration can be used to reveal a role of inflammation in many unexpected places. Aspirin is effective in blocking some forms of infertility, inhibiting miscarriages and ameliorating postpartum depression. So inflammation is a critical part of reproduction. But, also notice that depression is a symptom of chronic inflammation.

Cancer Requires Inflammation
High dose (IV) aspirin has been successfully used to treat cancer. Inflammation is required for cancer growth, because both use the same transcription factor, NFkB. The aberrant signaling of cancer cells would normally lead to programed cell death, apoptosis, but inflammation blocks apoptosis. Aspirin can in turn block NFkB and in the absence of inflammation, cancer cells die by apoptosis.

Inflammation is Self-Limiting
Aspirin also transforms the COX/lipoxidase system to produce anti-inflammatory prostaglandins/eicosinoids. Inflammation normally progresses into anti-inflammation. Blocking this progression leads to chronic inflammation and a shift from local to systemic inflammation with the rise of inflammatory interleukins in the blood stream.

Immune Response Requires Inflammation
The signal molecules (IL-1, IL-6, TNF) and transcription factor, NFkB, associated with inflammation were all initially identified in the development of lymphocytes. Hence, IL stands for interleukin, a hormone that triggers leukocyte (literally white blood cells or cells associated with the lymphatic immune system, i.e. lymphocytes) development. The nuclear factor, i.e. transcription factor, involved in expression of the large chain, kappa, of immunoglobulins in B cells, was called NFkB.

Genes Expressed by NFkB Cause Symptoms of Inflammation
About five dozen genes are under control of NFkB. Among these are COX-2, the enzyme that converts omega-6 arachidonic acid to inflammatory prostaglandins; iNOS, the enzyme that produces nitric oxide that dilates blood vessels to produce hot, red skin; and the inflammatory interleukins, IL-1, IL-6 and TNF, associated with autoimmune disease, fatigue and cachexia (wasting).

Autoimmunity and Allergy Start with Inflammation
Medical treatments focus on symptom abatement and ignore cause. What causes obesity, allergy or autoimmune disease? The answer appears to be chronic systemic inflammation plus exposure to unusual proteins. The unusual proteins are immunogenic, i.e. interact with the immune system to produce antibodies or reactive T-cell receptors, and are subsequently recognized as autoantigens or allergens, that are the targets for immune attack. Inspection of these autoantigens and allergens shows that they all have one thing in common, they bind to heparin via a strong heparin-binding protein domain that is typically a triplet of adjacent basic amino acids.

Heparin is a Short, Highly Sulfated Fragment of Heparan Sulfate
Commercial heparin is purified from the intestines of hogs and cattle. Heparin is released from mast cells (made fluorescent for microscopy using berberine) along with histamine and is released into the intestines to block pathogens from binding to the heparan sulfate that is part of the intestine surface. The heparin is anti-inflammatory and it contributes to minimizing the inflammatory response of the intestines to food.

Inflammation Reduces Heparan Sulfate Production
Pathogen-generated inflammation of the intestines reduces heparan sulfate production and increases immune response to food antigens. NFkB activation by inflammation turns off the production of some genes needed for heparan sulfate proteoglycan (HSPG) synthesis. Since HSPG is a major component of the basement membrane that holds tissues together, the reduction of HSPG results in protein loss (proteinuria) from kidneys, leaking of intestines, and disruption of the blood/brain barrier.

Reduction of HSPG Results in Immunological Presentation of Autoantigens/Allergens
Proteins are brought into cells by specific binding to protein receptors. In many cases, particularly involving signaling or growth factors, both the signal molecules and the receptors bind to heparin. In addition, there is a robust circulation of HSPG, which is secreted and internalized with a half-life of approximately six hours. The sweep of the HSPGs take heparin-binding proteins with them for internalization, e.g. HIV-TAT, heparanase, tissue transglutaminase. I think that this HSPG sweep under inflammatory conditions also internalizes basic autoantigens and allergens with strong heparin-binding domains. This internalization is the first step toward immunological presentation and the immune response to autoantigens and allergens.

Autoantigen/autoantibody/HSPG Complexes Kill Cells
Antibodies against self-antigens, autoantigens form antigen/antibody complexes that also bind to and cross-link HSPGs, because of the heparin-binding domains of the autoantigens. The large complexes may disrupt HSPG circulation and trigger apoptosis or abnormal physiology. There are many other examples of heparin-based complexes that are toxic, e.g. Alzheimer’s amyloid plaque, diabetic beta cell antibody complexes, celiac gluten/tRG antibody complexes, multiple sclerosis myelin antibody complexes, atherosclerotic plaque.

Anti-Inflammatory Diet and Lifestyle Protects
Dietary and lifestyle adjustments that minimize inflammation, e.g. low starch, no HFCS, low vegetable oil (except olive) and supplements of vitamins D & C, fish oil (omega-3) and glucosamine, reduce the risk of allergies/asthma, degenerative diseases and cancers. Simple, high level supplements with fish oil reduce numerous mental disorders, e.g. depression, ADHD; infertility, pre-eclampsia and postpartum depression; allergies, asthma; arthritis, atherosclerosis; burn recovery, septicemia and head injury.

Reducing Inflammation is a Panacea for Modern Diseases
Most modern diseases have an inflammatory component, because modern diets are rich in inflammatory components, e.g. starch/sugar, corn/soy oil, HFCS, trans fats, and exercise is minimal. The medical industry has not successfully promoted healthy eating and exercise; and in fact has promoted the devastating replacement of saturated fats with inflammatory polyunsaturated vegetable oils. Meat production has moved away from grazing on omega-3-rich plant vegetation to omega-6-rich corn and soy. Replacement of the corn/soy based agricultural economy would have predictably immense beneficial impact in reducing inflammation-based degenerative autoimmune diseases and cancers.

Friday, April 10, 2009

Cure for Cancer, Autoimmunity, Allergies, etc.







