Active thrombin produced by the intestinal epithelium controls mucosal biofilms

LLight

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Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.
Could vitamin K deficiency be a cause of gut issues?

I believe an association with inflammatory bowel diseases has already been found.
 
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@yerrag
I'm not sure you are "at risk" of vitamin K deficiency (probably not) or if this has anything to do with your issue but these scientists seem to have discovered a new role for thrombin in control of biofilm and planktonic bacteria around mucosa. I wondered if you might be interested.
 

yerrag

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@yerrag
I'm not sure you are "at risk" of vitamin K deficiency (probably not) or if this has anything to do with your issue but these scientists seem to have discovered a new role for thrombin in control of biofilm and planktonic bacteria around mucosa. I wondered if you might be interested.
Thanks for sharing. I'm not sure what I can do with this information though. My epithelium has long been invaded, and Zim beyond the point of Prevention but at the point of chasing out the invaders that have already institutionalized much like the US deep state has.
 
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I'm not sure what I can do with this information though.
Indeed, it's the same for me.

I wonder if K1 is more effective at inducing thrombin production than K2, and if it's a good thing even considering the information given in the publication above (and the one below).

Here is an hypothesis about another interesting supposed role of thrombin:

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

Well, clots are not really desirable but tissue repair, more interesting though. Maybe it can be a good thing if it's a totally controlled process.
 
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This book has been written by the author of the last publication:
Amazon product ASIN 0578822601View: https://www.amazon.com/Years-Lost-Medical-Advance-discovery/dp/0578822601/


And the only review:
This is a book to be carefully studied. A background in medicine or physiology would be very helpful but the author explains difficult concepts for the lay reader. Professor Hans Selye," the father of stress medicine,” made the observation that people with widely varying diagnoses exhibited similar symptoms. He founded a new physiology based on a lifetime of research but there wasn’t sufficient science in his day to finish the task replacing putative concepts with known facts. Nevertheless, based on Selye’s work everyone knows about stress although few understand it. Finally, 50 years after Selye and based on nearly 30 years of his own research, Lewis Coleman, MD, FAIS has figured out what happens in those gaps in our understanding of physiology, as well as why so many of our current working hypotheses are wrong. Dr. Coleman has now perfected the stress mechanism, the unified theory of disease that Selye envisioned. All the time, money and human toll invested in attempting to cure cancer and so many other diseases made little progress because it was all based on an incomplete and often flawed physiology. Now if medical schools, researchers and governments embrace and shift resources along the way Dr. Coleman informs us, healthcare in the near future will not only be far more effective, but it will also be kinder, more gentle, working with our bodies rather than overpowering us. So called “modern medicine” will languish in history in the way we think of medieval medicine now. This book is the new bible of medicine and requires and deserves intense study and adoption in every field of healthcare. Dr. Lewis S. Coleman is truly the father of 21st century medicine.
 
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Clearly, I'm not sure I would buy it. And we cannot even know its quality level.

Some of his publications are available for download on his research gate page.
 
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If Dr. Coleman is that good, I would be much more interested in reading him given his bona fides.

I wish we have a blacklist of authors that write garbage studies so we don't waste our time on them.

And have a list of authors that are highly recommended.
 
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Another comment for the book:

The major obstacle for this book is the price, but it's probably worth it if you want to really understand the body. The clearest way for me to evaluate how good or significant I think a book is without the immediate afterglow following the completion is to simply count the number of times I’ve re-read the book. I am continuously re-reading and taking notes on this book - I’m perhaps on my sixth time. This is very rare for me. It’s not just good, it’s a bombshell. Saying that I am mostly evaluating the quality of ideas expressed. Yet I can also say that the book is overall well written with a bias towards details which I prefer. I believe anyone with a highschool biology or physiology background would be able to sufficiently engage the material, but anyone can sort of test themselves by looking at his website: stressmechanism.com and then go to YouTube presentations. I happened to have found the website first and then was directed to the book. The core theory with mechanisms and some practical applications are extremely insightful and should not be missed by anyone interested in their own health or in how our medical and research system is searching in unhelpful domains and applying less than helpful theoretical applications. This book and its theory need to find their way into the minds of our current thought leaders and funding recipients and anyone actually trying to reduce human diseases. The core of Dr. Coleman’s argument has us looking at haemodynamics as the keystone in the human experience of health and disease. I have been focused on physiology of aging for a number of years and the most promising results are also focused on blood modification, but in general they lack the theory provided here. We should all be paying much more attention to carbon dioxide, nitric oxide, metabolism, blood viscosity, thrombin and thrombin inhibition to be able to cure most modern diseases. Before reading this book I was already convinced by epidemiology that all diseases have very similar mechanisms, and this book explains a or perhaps the major part of those mechanisms. Perhaps you’ve heard that aspirin reduces the risk of heart disease and cancer, this book explains the mechanism. If you’re paying attention to the anti-aging space you know that metformin is being tested as an all around anti-aging medicine...this book explains why and Why we should expect that berberine might also be a reliable alternative. If you are curious how we could better treat COVID patients or any patients on a ventilator this book explains it. Why is vitamin D seemingly therapeutic for most modern diseases? Why does therapeutic plasma exchange work to reduce the phenotype of age and why might leeches and blood donation be something we should all consider much more often. This book has THE mechanistic explanation. Hint: all answers are related to your blood and the stress response systems which dictates how viscous, or fluid, the blood is as well as how dilated the vasculature is and thus which cells get oxygen and nutrients. I recommend this book highly and hope others can also see the value put forth in it. If you want to have a better understanding of how to approach all; major diseases: cardiovascular disease, cancer, Alzheimers and many more conditions you need to read this book!
 
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@yerrag

Dr Coleman seems to be making an hypothesis about a connection between amyloid deposition and some diseases (among which hypertension and atherosclerosis).

To quote him:
Amyloid accumulation damages capillaries, which exaggerates blood flow resistance that manifests as essential hypertension.
Amyloid accumulates on the inner walls of arteries and induces tissue repair activity that causes atherosclerosis.
Amyloid causes atherosclerosis by accelerating capillary senescence, which undermines the pulsatile turbulence that mobilizes particulates from the inner walls of arteries. The particulate deposits incite inflammatory tissue repair activity that produces atheroscletoci plaques.

Could the enzymes you took have degraded some of these amyloid deposits (if this is the case), while the product of its degradation would have caused other issues?

Proteolytic enzymes are known to be involved in the formation and degradation of various monomeric proteins, but the effect of proteases on the ordered protein aggregates, amyloid fibrils, which are considered to be extremely stable, remains poorly understood. In this work we study resistance to proteolytic degradation of lysozyme amyloid fibrils with two different types of morphology and beta-2-microglobulun amyloids. We showed that the proteolytic enzyme of the
pancreas, trypsin, induced degradation of amyloid fibrils, and the mechanism of this process was qualitatively the same for all investigated amyloids.
[...] Another intriguing result of the work is that the cytotoxicity of amyloids treated with trypsin was not only failing to decline, but even increasing in the case of beta-2-microglobulin fibrils.

Not the same enzymes but we can wonder.
 

yerrag

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Thanks. The article is too deep for me, and long at 22 pages. But it reinforces my fear of using protease enzymes to lyse plaque.

I rathe degrade the necrotic core in the medit layer of blood vessels using vitamin E slowly.

I feel the use of proteolytic enzymes is a brute force approach to the problem of plaques. Since these enzymes do many things, it likely will do things we were.not expecting it to do. Whatever it does that wasn't intended, it is likely not noticed by the person taking it.

But if I were to take enzymes for plaque, I wouldn't take a large dose aimed at getting quick results but smaller doses that takes time to have an effect.

Having said that, I wonder if the study used a heavy dose of trypsin.
 
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LLight

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But if I were to take enzymes for plaque, I wouldn't take a large dose aimed at getting quick results but smaller doses that takes time to have an effect.
Indeed, it seems to be a more cautious way to go.
 

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