SPED meets Retinoid Toxicity - round one.
Endothelial and epithelial cell differentiation will be the location for the meet-up.
Walter M. Chestnut has been talking a lot about what he has termed Spike Protein Endothelial Disease (SPED) - endothelial destruction by the chimeric spike protein. SARS-CoV-2 infections seem to like endothelial cells that line blood vessels a lot, and it leads to autoimmune like tissue destruction of our body vascular membranes.
Flow chart of SPED meets Retinoid Toxicity:
SARS-CoV-2/chimeric spike causes damage to endothelial cells lining blood vessels.
LongCovid symptoms ensue. Tissue destruction doesn’t feel good.
LongCovid can also include ME/CFS symptoms.
ME/CFS symptoms may be seen following Epstein-Barr infection (mononucleosis is another name for the flu like infection).
The Epstein-Barr virus (EBV) affects the DHRS9 gene of the person infected in a way that leads to more activation of Retinoic Acid from retinol. The Retinoic Acid then can cause epithelial cell differentiation, which the EBV virus can then enter and colonize. The EBV virus cannot infect undifferentiated cells.
“Abstract: Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBV-positive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1.” (Jones, et al, 2007) (2)
Question for the search engine - Can Retinoic Acid cause the differentiation of endothelial cells. Answer - Yes. (Chen, et al, 2015)(1)
Theory - ME/CFS is being seen in LongCovid in some people because their genes were changed in a way that is causing overactivation of Retinoic Acid to support more differentiation of endothelial cells in order for SARS-CoV-2 to be able to infect them.
What if SARS-CoV-2 or spike is promoting the activation of Retinoic Acid in order to promote differentiation of cells into endothelial cells which it can infect?
What if that is leading to chronic overactivation of Retinoic Acid and the myriad symptoms that can occur with Retinoid Toxicity? And which seems to include ME/CFS but that isn’t on the Retinoid Toxicity symptom list officially (no peer review journal reference that I have found other than the EBV link, (Jones, et al, 2007). (2)
Related post of mine re symptoms of Retinoid Toxicity: Retinoic acid & toxicity - dosing - how much is too much for normal health? (substack.com)
Walter has also been stressing the similarity of CoV symptoms with radiation damage - yes, I agree, they both cause inflammation which can escalate into a hyperinflammation positive feedback loop - self-sustaining rather than with normal negative feedback controls.
Radiation and other stimuli can open TRP channels and cause excess entry of calcium into cells where it can cause overactivity and may even lead to cell death. The spike protein disables TRP channels at the ankyrin repeat domains so it is hard to know exactly how much dysfunction is occurring due to disrupted TRP channels. It would reduce magnesium absorption in the gut. Chelated magnesium supplements may bypass the problem, or I take Epsom salt soaks about once a week. Twice a week might be better, less than once a week is worse - I start getting mood and muscle cramp symptoms if I wait too long for a magnesium sulfate (MgS) soak. The sulfate is also protective for cardiovascular and membrane health.
“The Spike Protein causes the exact same damage to the endothelium as if it had been irradiated.” - Walter M Chestnut *
True. Hyperinflammation is hyperinflammation whatever the cause was and hyperinflammation will lead to cancer of other chronic degenerative conditions, no matter what the cause of the inflammation was. *That title is linked in a more recent post of Walter’s:
(https://wmcresearch.substack.com/p/the-spike-proteins-mimicking-of-endothelial)
Addition - Spartacus explains the endothelial dysfunction risk in detail and understandable for non-scientists, maybe. He talks fast, pause and relisten. Anyone with Metabolic Syndrome type risk factors would be more at risk, and he says ethnic blacks may also be more at risk due to lower Nitric Oxide levels as a general tendency/genetic difference. The BHMT gene allele that I have is also more frequent in blacks or whites than Asians.
Spartacus mentions what would help - “activating the Nrf2 pathway”. Inflammation whether spike, or EMF, or a stressful day, will all inhibit Nrf2. Pomegranate peel, quercetin, delphinidin, sulfarophane, etc - many fruits and vegetables, herbs and spices, will help protect against the hyperinflammation caused by spike and/or modern life and/or genetic differences in detox ability.
My first major Substack post was about Nrf2 and NF-kB. They are critically important to know about if your goal is to reduce hyperinflammation and prevent degenerative changes.
Potential list of causes of hyperinflammation. *note EMF = a source of radiation, basically. 5G is likely making us sicker.
We have no shortage of potential causes of inflammation in modern life. Radiation, EMF, or a bad sunburn are causes of inflammation. Spike is too.
Endothelial dysfunction is the standard medical term.
What does endothelial damage look like?
The endothelial cells line the internal layer of blood vessels so we wouldn’t see it. It can cause hypertension - high blood pressure, stiffer blood vessels. (*Most of this post was written last night and I have added some updates this morning.)
The Linus Pauling website (Endothelial dysfunction) has useful reference pages for nutrients, minerals, and some conditions. Endothelial dysfunction is an early sign of heart disease, and it can be reversible. Worsening inflammation could lead to atherosclerosis and increased stroke risk. Endothelial dysfunction involves “an "activated endothelium" that is in a state of inflammation, growth, and thrombosis (blood clotting).”
That might suggest bruising too easily could be a later symptom of endothelial breakdown. Like from crossing your legs or wresting your elbows on your knees?
Why are my knees bruised on top? Pressure seems to occur from crossing my legs. Another person, a male, mentioned on Twitter pre-my-suspension having a similar bruised top of the knee problem after CoV. I have had similar bruised knees at times since CoV but currently these bruises are fairly new and I have no idea what I might have done to cause them. Lifting a big heavy box might leave a bruise from resting the lower edge on my legs when paused a momet, but I haven’t done much heavy lifting since my sunburn pox got bad (which are better now, basically all healed, mostly). Sitting with my laptop on my lap tends to increase edema/warmth/puffiness in my thighs. Using a large wooden cutting board under the laptop seems to insulate the effect somewhat but I try not to sit with a laptop on my lap much anymore.
Other symptoms I have currently that suggest internal membrane break down: My right leg is also a little swollen looking in the photo from edema. I have an old bruise that never healed correctly on the back of that leg and it gets worse without nightly elevation and serrapeptase. Sitting too much and harder edged chairs make it worse (the old wound is right where the edge of a chair is). It hurts chronically now, aches like a bruise. If the edema throughout the leg gets worse that hurts too and can affect my walking when more severe.
I ran out of serrapeptase and nattokinase briefly and it got worse. Bromelain does not seem to help as much, though it is good for respiratory congestion. I take one serrapeptase in the middle of the night when I wake up at some point - on an empty stomach is better for cardiovascular benefits; with food aids digestion of that meal. Serrapeptase without food may be helping keep fibrotic build up within the body in check.
Nutrients and flavonoids that may be needed to reverse endothelial dysfunction:
The Linus Pauling website (Endothelial dysfunction) has some nutrient guidance: Deficiency of nitric oxide is a factor. Vitamin C is recommended and certain flavonoids to increase nitric oxide (like pomegranate, more on that next). Skipping my magnesium bath for too many days may also be part of my bruised knee issue and I smoke too much - true. I have noticed symptoms related to smoking in the past (scalp eczema) worsening.
I should try the lower heat vape again (*it worked pretty good this morning, just where is the correct USB cord for recharging?) and stop the toxins part of medical marijuana use. Inhaled cannabinoids are needed for the mast cell inhibition which helps the histamine excess tendency immensely (better than pomegranate juice). Digestion changes the cannabinoid molecules enough to matter for histamine symptom relief.
I am not getting my cheerful juice in daily either or my pomegranate/other herbals tea - slacking on my complex self-care routine. I have been trying to get the methyl B group in daily the niacin and melatonin and some of my other supplements. It is hard to do so many things every day - true. But health is better than pain. (*The Cheerful Juice is kind of acidic on my sensitive gut now, made some first thing this morning. I need to modify the recipe more or just sip smaller amounts.)
I guess I should make myself some tea, STAT:
The mechanism by which pomegranate may widen your blood vessels is possibly its effect on nitric oxide synthase enzymes. This family of enzymes increases the availability of nitric oxide, a vasodilator in your body.
Does Pomegranate Expand Your Veins? | Healthy Eating | SF Gate
I decided on pomegranate peel tea made with mango peel, thyme, and dandelion root (not much it is also a diuretic) too. The mango peel is anti-inflammatory also and adds a nice flavor. Thyme is a GABA promoter, calming, and has a nice flavor. But I added a spoon of pure maple syrup and so the flavor is predominantly maple. I make a small pot of tea and keep it in the fridge and use a little with hot water, so I don’t have to make fresh each time I have some. The dried peels and medicinal tea goal needs a longer steep, about 20-30 minutes.
The diuretic effect from the pomegranate peel and dandelion root will help clear the leg edema hopefully and promote nitric oxide production.
*Morning after update - success, the right calf is less edematous - price I paid - waking up in the middle of the night to pee and drink more water at least six or more times. I am exhausted. Always plan ahead and take your diuretic herbals in the morning with plenty of water throughout the day.
Potency check - one quart of tea was made with 4 1/8th inch pieces of dandelion root and 4 1/4-1/2 inch pieces of outer pomegranate peel. I don’t think the thyme or mango peel add more diuretic effects, but I am not sure. Pomegranate peel and dandelion are very potent. Dandelion leaf, flower, stem or root all have the medicinal phytonutrients. Eaten as springtime greens in a salad seems to have less of the diuretic effect though and was tasty, a little peppery rather than just bitter greens.
Membranes and Inflammation are so important that I have two webpages on the topic.
Membranes and Inflammation (jenniferdepew.com)
Membranes (and glyphosate) (jenniferdepew.com)
My webpages about TRP channels are on effectivecare.info, page G3. Relaxation and Stress, and G5. Pre-eclampsia and TRP channels. Page G4. Autoimmune disease and vitamin D provides some helpful background information for reducing risk of developing new autoimmune sensitivities from prenatal or other autoimmune risks such as chimeric spike protein issues.
NUTRIENTS ARE A TEAM!
To have adequate vitamin D we need to first have adequate magnesium and protein transport carriers to hold a back stock in the inactive form. In order to have adequate magnesium we need to be able to absorb it in the gut or use topical sources, and we also need adequate phospholipid and protein for transport carriers to keep a backstock of magnesium that is not electrically active - otherwise the body has to excrete it in urine.
This is an important post: To have optimal Magnesium needs Protein and Phospholipids too, (transcendingsquare.com).
Cardiovascular health is not possible without adequate magnesium.
Facts matter.
This post is somewhat of a summary of my Retinoid Toxicity theory
Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance. Please seek a functional health practitioner for individual health care guidance.
Reference List
(Chen, et al, 2015) Chen P, Chen JZ, Shao CY, Li CY, Zhang YD, Lu WJ, Fu Y, Gu P, Fan X. Treatment with retinoic acid and lens epithelial cell-conditioned medium in vitro directed the differentiation of pluripotent stem cells towards corneal endothelial cell-like cells. Exp Ther Med. 2015 Feb;9(2):351-360. doi: 10.3892/etm.2014.2103. Epub 2014 Dec 3. PMID: 25574197; PMCID: PMC4280952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280952/
(Jones, et al, 2007) 11. Jones RJ, Dickerson S, Bhende PM, Delecluse HJ, Kenney SC. Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9. J Biol Chem. 2007 Mar 16;282(11):8317-24. doi: 10.1074/jbc.M608667200. Epub 2007 Jan 22. PMID: 17244623. https://www.jbc.org/content/282/11/8317.long
(Marasciulo et al, 2006) Marasciulo FL, Montagnani M, Potenza MA. Endothelin-1: the yin and yang on vascular function. Curr Med Chem. 2006;13(14):1655-65. doi: 10.2174/092986706777441968. PMID: 16787211. https://pubmed.ncbi.nlm.nih.gov/16787211/
*The extra numbers 9- 11- 12- are the references in Retinoid Toxicity, my original blog series on this topic. https://docs.google.com/document/d/1vmLyBzx_joI2sT83YUfnWAKrZVd6UTXZhfUDZw-RoA8/edit?usp=sharing and a few were copied to this post: Retinoic acid & toxicity - dosing - how much is too much for normal health? (substack.com)
I've given this some thought. A few things:
-SARS-CoV-2's E and 3a proteins act as calcium ion channels. Intracellular calcium influx is an essential part of the life cycle of coronaviruses, and basically all severely-ill COVID-19 patients have noticeable hypocalcemia. This is very likely why Vitamin D repletion seems to help; it pumps calcium back out of cells. If Vitamin K is taken as well, it fixes the excess calcium in bone and teeth.
-SARS-CoV-2's disruption of ACE2 also disrupts the kallikrein-kinin system. ACE2 normally breaks down des-arg9-bradykinin (DABK). As SARS-CoV-2 fuses with ACE2, the DABK starts building up, and when it acts upon the bradykinin receptor, it promotes arachidonic acid release and intracellular calcium pathway activity, which leads to isoprostane formation, superoxide release, and severe oxidative stress.
-COVID-19 causes intussusceptive angiogenesis:
https://www.sciencedirect.com/science/article/pii/S2531043721001604
Look up how SARS-CoV-2 uses neuropilin-1 as a secondary host factor:
https://www.science.org/doi/10.1126/science.abd2985
Then, look at the relationship between neuropilin-1 and transforming growth factor beta, and the relationship between TGF-β and vascular endothelial growth factor (VEGF):
https://pubmed.ncbi.nlm.nih.gov/18436584/
https://www.nature.com/articles/s41467-021-22210-3
As for radiation injury, I have spoken with PhD biologists and virologists on this, including a guy who works for NASA, analyzing the effects of cosmic radiation on the health of astronauts, and he straight-up admitted to me, well over a year ago, that the pathways of COVID-19 injury, as I'd described them to him, resembled the effects of radiation injury. Walter is on the right track.
Basically everyone who suffers from severe COVID-19 has a noticeable dip in nitric oxide and an increase in nitrotyrosine:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106525/
Nitrotyrosine is mostly formed when peroxynitrite nitrates tyrosine to make it. It's basically proof positive that nitric oxide is being consumed in a reaction with superoxide. This has a very close relationship to what Martin L. Pall terms as "NO/ONOO- Disease":
https://www.clinicaleducation.org/resources/reviews/how-can-we-cure-noonoo-cycle-diseases-a-review/
This is a vicious cycle where peroxynitrite (ONOO-) uncouples endothelial nitric oxide synthase (eNOS) by destroying the BH4 cofactors needed for eNOS to synthesize nitric oxide. Uncoupled eNOS produces more superoxide instead of nitric oxide, which reacts with any available nitric oxide to form peroxynitrite, which uncouples more eNOS enzymes, which produce more superoxide. This goes in a loop until all the nitric oxide is gone.
In COVID-19, this is a bad thing, because SARS-CoV-2's replication is directly inhibited by nitric oxide. It is as if the virus is trying to force cells to form radicals to get the nitric oxide out of its way. This is also true of SARS-CoV:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111989/
Peroxynitrite has no beneficial effect against the Spike. As soon as the nitric oxide is all gone, the virus starts replicating even faster. This is the fundamental reason why SARS-CoV-2 affects people with pre-existing endothelial dysfunction (obese, diabetic, hypertensive, and/or aged, etc.) before everyone else. Their vascular endothelial tissue is already teetering on the edge. COVID-19 comes along and pushes them off the cliff.
To make matters worse, SARS-CoV-2 actively inhibits the Nrf2 pathway:
https://www.nature.com/articles/s41423-022-00887-w
When I had COVID-19, I took NAC, curcumin, resveratrol, quercetin, Vitamin D, Benadryl, and Pepcid. The latter two are not just histamine blockers, they're powerful antioxidants and inhibitors of the Fenton reaction. I'm basically fine.
There is a very significant rationale here for antioxidants and Nrf2 activators to be a standard part of every COVID-19 treatment regimen.
Do you have some recipes you'd like to share?
I'm trying to build a cookbook from different sources.