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Water Structure, Osmolytes And Cancer

Discussion in 'Cancer' started by LLight, Aug 23, 2019.

  1. OP
    LLight

    LLight Member

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    Water in malignant tissue, measured by cell refractometry and nuclear magnetic resonance. - PubMed - NCBI:

    "Under these conditions the average water content of the cytoplasm of normal liver cells is calculated to be 87%. The cytoplasm of the liver tumour cells, on the other hand, have an average water content of over 92.5% and the cytoplasm of the cells of the ‘host liver tissue’ (tissue immediately adjacent to the tumour tissue) has an average water content of 89%."

    "This meant that just over one third of all the intact living tumour cells examined had cytoplasmic refractive indices below 1.350, and consequently contained significantly more than 93% water. And as the cytoplasm of some of these cells appeared quite markedly bright in this mounting medium it seems likely that the upper end of the range of their water contents was at least 94% and probably nearer to 95%. This serves to indicate just how ‘watery’ these spherical cancer cells had become-very considerably more aqueous than any normal animal cells ever so far encountered. It also means that the averge refractive index of the cytoplasm of these cells is most unlikely to have been higher than 1.351, which implies that, at its very lowest, their average water content was in the region of 92.5%."

    "One may legitimately ask, however, how much of the total water in the tissue is intracellular and how much is extracellular. In our present state of knowledge no answer is forthcoming. It could be that the NMR relaxation time measurements almost exclusively measure intracellular water; and the striking resemblance of Figs. 3A and 3B would seem to support this view; but this is in fact most unlikely because all the specimens removed from the livers for testing were ‘wet’ with extracellular fluid. Unquestionably some of their water was derived from the cellular environment. Extracellular liquid might be expected to be particularly in evidence in the tumour- bearing tissue since it always becomes to a greater or lesser degree inflamed. So probably both the cells comprising a tissue and their external environment become hydrated when a tumour develops in that tissue."

    "What causes the increase in intracellular and extracellular water in these tumours and in the immediately adjacent tissues, which we have been able to demonstrate ? One possible cause can definitely be ruled out; it cannot be due to a change in the tonicity of the extracellular fluids causing the cells to swell and their contents to become more diluted. If this were so, removing the cells from the tissue and isolating them in isotonic media would cause them to contract again, and no difference between the refractive indices of the cytoplasm of the tumour cells and the normal cells from which they were ultimately derived would be apparent. Among the widely divergent views held on the aetiology of cancer there seems to be a certain measure of consensus that the cell membranes of malignant cells are probably abnormal with respect to their permeability properties, and the findings reported here could be interpreted as providing some additional support for this view."
     
  2. OP
    LLight

    LLight Member

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    Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

    "This paper postulates that water structure is altered by biomolecules as well as by disease-enabling entities such as certain solvated ions, and in turn water dynamics and structure affect the function of biomolecular interactions. Although the structural and dynamical alterations are subtle, they perturb a well-balanced system sufficiently to facilitate disease. We propose that the disruption of water dynamics between and within cells underlies many disease conditions. We survey recent advances in magnetobiology, nanobiology, and colloid and interface science that point compellingly to the crucial role played by the unique physical properties of quantum coherent nanomolecular clusters of magnetized water in enabling life at the cellular level by solving the “problems” of thermal diffusion, intracellular crowding, and molecular self-assembly. Interphase water and cellular surface tension, normally maintained by biological sulfates at membrane surfaces, are compromised by exogenous interfacial water stressors such as cationic aluminum, with consequences that include greater local water hydrophobicity, increased water tension, and interphase stretching. The ultimate result is greater “stiffness” in the extracellular matrix and either the “soft” cancerous state or the “soft” neurodegenerative state within cells. Our hypothesis provides a basis for understanding why so many idiopathic diseases of today are highly stereotyped and pluricausal."

    "The vast medical research literature contains extensive documentation of dysfunctional changes in biomacromolecular structure and activity seen in chronic and infectious diseases. Molecular-level phenomena described include inappropriate gene activation and protein synthesis driving uncontrolled division of cancer cells, diversion of this same gene expression process to proliferate infectious viruses, and beta-amyloid protein tangles characteristic of Alzheimer’s disease, to name just a few. Details for individual diseases vary, but the common feature of molecular mechanisms offered for all of them is emphasis on the roles of macromolecules and their non-aqueous substrates or ligands, with little or no attention given to water, the most abundant molecule in the body and the most essential for all forms of life. In this paper, we present an alternative view of disease etiology that places water at the center of the stage. We propose that a major cause of inflammation and disease is disruption of normal water structures between and within cells, which then gives rise to the pathological macromolecular changes reported in the literature."
     
  3. OP
    LLight

    LLight Member

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    Just saw this book has been published recently, Seems to be in the pure spirit of this post: Cancer and the New Biology of Water (https://www.amazon.com/Cancer-Biology-Water-Thomas-Cowan/dp/1603588817)

    "In Cancer and the New Biology of Water, Thomas Cowan, MD, argues that this failure was inevitable because the oncogene theory is incorrect―or at least incomplete―and based on a flawed concept of biology in which DNA controls our cellular function and therefore our health. Instead, Dr. Cowan tells us, the somatic mutations seen in cancer cells are the result of a cellular deterioration that has little to do with oncogenes, DNA, or even the nucleus. The root cause is metabolic dysfunction that deteriorates the structured water that forms the basis of cytoplasmic―and therefore, cellular―health."

    “An eye-opening book. With insights developed from years of medical practice and original thinking, Dr. Cowan presents evidence for an unsuspected protagonist in the development of cancer: water. He not only argues that the gel-like state of the cell, created by water’s structure, serves as the basis of cellular organization and function, but also that any compromise of that gel-like state can trigger the development of cancer. He connects well with readers, weaving threads of sensitivity and humanity through the fabric of the book. At the same time, he is not shy to criticize the cancer establishment for its narrow focus on genetics—which has arguably produced few gains over many decades. Highly recommended, not only for those interested in cancer—who isn’t?—but also for anyone interested in logical thinking in science.” —GERALD H. POLLACK, PhD, professor, University of Washington; author of The Fourth Phase of Water
     
  4. OP
    LLight

    LLight Member

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    Kosmotropes and Chaotropes:

    "Chaotropes break down the hydrogen-bonded network of water, so allowing macromolecules more structural freedom and encouraging protein extension and denaturation. Kosmotropes are stabilizing solutes which increase the order of water (such as polyhydric alcohols [307], trehalose, trimethylamine N-oxide, glycine betaine, ectoine, proline, taurine [3185], and various other zwitterions) whereas chaotropes create weaker hydrogen-bonding, decreasing the order of water, increasing its surface tension (but see anomaly) and destabilizing macromolecular structures (such as guanidinium chloride and urea at high concentrations).

    Glucose clearly acts as a kosmotrope, enhancing both hydrogen-bonding and hydrophobic interactions [283]."
     
  5. OP
    LLight

    LLight Member

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    Warburg effect-damping of electromagnetic oscillations. - PubMed - NCBI

    "Disorder in cancer cells and tissues in comparison with healthy cells and tissues suggests that the organization mechanism is disturbed, the acting forces changed and their coherence weakened. The coherent electromagnetic field is a fundamental component of the action forces, and its disturbance can condition cancer development. We present a physical model of transformation of the ordered water layer connected with mitochondrial function and dysfunction, based on published experimental data. Reduced oxidative ATP production and transfer of hydrogen ions from the matrix of dysfunctional mitochondria to the cytosol and a diminished membrane potential result in transfer of the working point to a higher pH region and reorganization of the ordered water layer connected with a potential barrier formed by a charge layer on the inner membrane. The reorganized ordered water layer releases electrons which are transferred to its outer rim at the cytosol. The electrons form a conductive region which damps electric oscillations of microtubules. Lowered power and disturbed coherence of electromagnetic oscillations result in a disorder of cellular organization—the final effect of mitochondrial dysfunction. Warburg’s reference to “more structure” is provided by functional mitochondria in healthy cells with the actual inner membrane potential higher than certain critical value. In a healthy cell, the absolute value of the apparent potential of the mitochondrial inner membrane is lower than that in a Warburg effect cancer cell. The differences between the apparent and actual potential are caused by the potential of the ordered water layers. In a Warburg effect cancer cell, the ordered water layer is reorganized and the water layer releases electrons, efficiently damping electromagnetic activity. The electromagnetic organization forces are weak, and coherence is disturbed. In the reverse Warburg effect cancers, the mitochondrial dysfunction and damped electromagnetic field occur in associated fibroblasts transporting energy-rich metabolites to the cancer cell whose electromagnetic field exhibits high energy with fluctuating power level and low coherence."

    Structure of water is connected to mitochondria disfunction.
     
  6. Inaut

    Inaut Member

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    Error - Cookies Turned Off

    Can we put a list together of naturally occurring osmoltes? I was listening to an old Ray Peat/KMUD interview where he was discussing the the watery nature of cancer cells and tumors and it once again peaked my interest here.

    Taken from the paper above...

    Naturally Occurring Osmolyes:
    Trehalose
    Sorbitol
    Taurine
    Glycine betaine
    Sarcosine
    Raffinose
    TMAO
    Glycerol
    Proline
    Glycine
     
  7. yerrag

    yerrag Member

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    That's a long list. I'm using taurine now, but I'm thinking of getting glycine betaine, aka TMG (trimethylglycine).

    Have been thinking of going back to dry fasting once my blood sugar issues go back to normal. Then I could hope to trigger NFAT5 transcription and be able to effect LL-37 so that it would be able to neutralize LPS without triggering a TLR4 inflammatory response. @LLight it's finally sinking into my thick skull what you've been telling me about how this would help me deal with lowering my blood pressure.

    I'm already using taurine as I'm hoping its use to keep albumin from being excreted can be realized as I have to boost my serum albumin to increase blood volume. LL-37 may also help as it neutralizes LPS, and this would keep albumin from having to bind with LPS as a way to transport LPS into the liver on the way to being excreted. And to cover all my bases, I'd have to lessen the use of albumin as an anti-oxidant by supplementing with anti-oxidants such as vitamin C and vitamin E. Taurine in itself has some anti-oxidant properties, particularly with the ROS involved in phagocytic activity involving renal cells.

    I'm also taking more gelatin now from pork and beef tendons, as I consider it a more endotoxin-free source of gelatin, whih would provide some glycine and proline.

    What else of the osmolytes should I add that wouldn't be superfluous?
     
  8. OP
    LLight

    LLight Member

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    There are also : carnitine (Carnitine: an osmolyte that plays a metabolic role. - PubMed - NCBI), and (Intracellular Organic Osmolytes: Function and Regulation), ectoine (produced by bacteria), inositol, choline, creatine.

    I also suspect that boron and thiamine are involved in the hyperosmotic stress response. Thiamine transporters seem to be upregulated in such situation and boron seems to be helpful with respect to dehydration/high salt stress for plants (and seems to induce the immune system in the same way than NFAT5, but in the case of RA, NFAT5 is "pathologically" associated while boron seems to be therapeutic. We might infer that boron is used in the immune response for the resolution of RA). There might be more.

    Also, abscisic acid, a retinol analogue, see e.g. Abscisic acid is a toxic retinoid aka Poison/"Vitamin A" compound lol, is involved in the response to dehydration (for example, Increased Abscisic Acid Biosynthesis during Plant Dehydration Requires Transcription).
     
  9. Inaut

    Inaut Member

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    Camphor too :) right

    osmo@llight :)
     
  10. OP
    LLight

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    Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells

    "
    Background
    Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence.

    Results
    A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection. We show that desiccation increased ecdysone synthesis in MTs, while inhibition of ecdysone synthesis or ecdysone receptor expression, specifically within MTs, prevented induction of PGRP-LC and reduced protection from bacterial infection. Additionally, aged flies are constitutively water-stressed and have elevated levels of ecdysone and PGRP-LC. Conversely, adults aged at high relative humidity show less water loss and have reduced expression of PGRP-LC and AMPs.

    Conclusions
    The Drosophila renal system is an important contributor to host defense and can modulate immune responses in an organ autonomous manner, responding to environmental changes such as desiccation. Desiccation primes immune responsiveness by elevating PGRP-LC expression specifically in MTs. In response to desiccation, ecdysone is produced in MTs and acts in a paracrine fashion to increase PGRP-LC expression, immune responsiveness, and improve host defense. This activity of the renal system may contribute to the immunosenescence observed in Drosophila."

    Maybe if it's combined with fasting, there is no immunosenescence: Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence
    "In contrast, FMD cycles followed by refeeding are emerging as both an effective and feasible intervention with the potential for long-term and wide use. They are also emerging as potentially powerful interventions in the treatment of other age-related diseases and conditions including immunosenescence."
     
  11. OP
    LLight

    LLight Member

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    At this point, should change my username for that :):

    Camphor is an osmolyte too?
     
  12. Inaut

    Inaut Member

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    Maybe I just made that up.... I though I read it ... apologies for misguiding :(

    I know it has effects on the structure of the cell so maybe it’s a semi-osmolyte

    No more jumping to conclusions, I get too excited some times
     
  13. OP
    LLight

    LLight Member

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    No problem man :):

    If you find back what gave you this idea, do not hesitate to post it!
     
  14. OP
    LLight

    LLight Member

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    Shower thoughts:

    I know the Randle cycle opposes fat and carb metabolism but wouldn't the issue be more a fundamental incompatibility between carbs and proteins? Carbs allow to spare proteins, and vice versa via gluconeogenesis. They seem to be able to be interchanged, so they might also have antagonist metabolisms?

    If I understand well what the Randle cycle implies: if you eat fat and carbs at the same time, your body not being able to use it simultaneously should secrete insulin such that fat remains locked in adipocytes. When you're low in glucose, your insulin decreases so that free fatty acids replace carbs for fuel. So the Randle cycle is more about the body needing to use insulin to regulate between glucose and fat metabolism, because you should be burning one fuel at a time. Randle cycle is not really telling whether your insulin secretion will be problematic, which is governed more by your insulin sensitivity. Maybe if you are insulin sensitive, Randle cycle is not a problem in and of itself. Hyperinsulinemia/insulin resistance seem to be implied in all major diseases, and I don't know if too high levels of insulin is the real cause or just a correlation, but it's a fact, too much insulin is associated with major chronic diseases.

    People seem to regain their health, at least in the short term, with vegan/low fat (Ray Peat promotes relatively high amount of proteins but I think it's generally not the case with other version of low fat, for example with Kempner's diet?) or carnivore/low carb diets. These diets tend to be either rather low protein (and low fat but not always, some vegans eat fats like olive or coconut oils, avocado or cocoa fats, not sure whether they have the same health improvements than low fat vegans, maybe not) or rather low carb. Not saying that you cannot be healthy otherwise, but these interventions seems to feature such specificities in general. And I believe these interventions are associated with less insulin secretions. Of course they allow to escape the Randle cycle, which should explain a major part of the insulin decrease, but there might be more because usually, insulin sensitivity (measured with glucose loading test or the Trig/HDL ratio) is restored or greatly improved (and even if there is no weight loss). Some people explain that by the fact that hyperinsulinemia (which is reversed) is causing insulin resistance, because too much of an hormone causes resistance of the receptor, but I'm not sure if it's really the case, it's more logical to think that the reverse is true, that it's insulin resistance that creates hyperinsulinemia.

    So there might also have an effect of not consuming too much proteins and carbs at the same time when it comes to insulin sensitivity.

    What I find interesting is that, if I'm not mistaken, osmolytes (if I understand well, they allow structuring the water in the cell, which could be an important condition for a proper cell functioning and thus oxidative metabolism and insulin sensitivity) seem to come from rather the carbs or the protein "kingdoms" (but not fat), some seem to derive from glucose while other seem to be amino acids. So I was thinking that maybe, an incompatibility between glucose and proteins metabolism could stem from that two different origines of osmolytes. Maybe osmolytes can be classified in two parts and these are not able to be used in a cell at the same time.
     
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