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Reduced glycolytic reserve in isolated natural killer cells from ME/CFS patients: A preliminary investigation, Nguyen et al, 2018

Discussion in 'BioMedical ME/CFS Research' started by Indigophoton, Jul 10, 2018.

  1. Indigophoton

    Indigophoton Senior Member (Voting Rights)

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    https://www.ncbi.nlm.nih.gov/pubmed/29981562

    The DOI (digital object identifier, aka ID number) for this doesn't seem to work, so I'm not sure anything beyond the abstract has been published yet.
     
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  2. Trish

    Trish Moderator Staff Member

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    Hmm. So they took 6 ME/CFS patients and 6 healthy controls, measured lots of things to do with NK cells and energy, but are only reporting statistical significance for one of those things. So it's very much a tiny preliminary study.
     
  3. Hutan

    Hutan Moderator Staff Member

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    Yes.

    But that looks like quite a big difference in glycolytic reserve in this sample - the standard deviations suggest discrete results. I think a number of researchers are using the Seahorse tool to research ME. This is something to keep an eye out for as they report their results.

    I don't know what a glycolytic reserve is or its relevance, of course.
     
    Last edited: Jul 10, 2018
  4. Indigophoton

    Indigophoton Senior Member (Voting Rights)

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    According to the instruction manual for the Seahorse test used in this paper,
    So the reduced glycolytic reserve seen in these preliminary results suggests the ME patients' NK cells have a significantly reduced ability to respond to energetic demand.

    Eta: I wonder if some of this might possibly intersect with Booth and Myhill's work on mitochondrial ATP production.
     
    Last edited: Jul 10, 2018
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  5. Trish

    Trish Moderator Staff Member

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    So it looks like it's basically saying glycolysis, which is the low energy producing anaerobic first stage of energy production in the cells is going too slowly, so not producing enough substrate for the higher energy producing aerobic stage that happens next in the mitochondria. So the cells can't produce energy fast enough to meet demand. I think...
     
  6. Amw66

    Amw66 Senior Member (Voting Rights)

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    Uncoupling of supply and demand ?
    There could be a number of potential mechanisms?
     
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  7. Rossy191276

    Rossy191276 Established Member (Voting Rights)

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    I had ‘moderately reduced glycogen levels’ on my muscle biopsy even though I eat quite a bit of carbs. I am wondering whether this might be a common finding in ME in muscle tissue as well...
     
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  8. Simone

    Simone Senior Member (Voting Rights)

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    With the millions in funding this group has, it’s so frustrating that they often publish such tiny studies.
     
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  9. Sean

    Sean Senior Member (Voting Rights)

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    I think the goings on in the extra-cellular matrix will tell us a lot, possibly including mechanically too.
     
  10. Milo

    Milo Senior Member (Voting Rights)

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    Pilot studies are meant to be small. It is designed so they can explore hypothesis without too much financial and human ressource investment. Since they seem to have found something, it will give them power to apply for some grants to either expand on a bigger cohort, or try the same experiment on other cell type, or compare to other similar diseases.

    I am thankful that this team is exploring avenues that haven’t been researched through scientific experiments, through hypotheses and they are also teaching health science students about the disease. We need and deserve so much more research.
     
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  11. Trish

    Trish Moderator Staff Member

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    Perhaps the point is that this research group seem to have done lots of small studies and got them published, and got lots of funding, but don't seem to have done any large studies.
     
  12. Simone

    Simone Senior Member (Voting Rights)

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    Yes, that’s the point I was wanting to make, but didn’t! Thanks, @Trish :)
     
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  13. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The problem is success on a pilot study isn't actually statistically valid to justify further research, it simply shows that such an experimental design is possible.
     
  14. Londinium

    Londinium Senior Member (Voting Rights)

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  15. Amw66

    Amw66 Senior Member (Voting Rights)

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    I think there is a definite intersection. They too found an uncoupling of supply and demand; more interestingly, for some they found that ATP was being flung out of the mitochondria faster than it could be replenished ( ostensibly due to substrate issues)- this could be ATP as puringenic signalling, instigating AMPK activation and downregulation ...
     
  16. FMMM1

    FMMM1 New Member

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    Jumbled thoughts:

    Prof Don Staines presented data, at the Invest in ME Research International ME Conference 2018, indicating problems with calcium regulation. I assumed that they would/had published that data. I assume that the energy problems demonstrated in this paper are proposed to be a consequence of the calcium regulation problem.

    This glycolysis study looks similar to other studies i.e. those referred to above (C Tomas etc); therefore, I'm not clear what's new. However, a study in effect confirming problems is still useful i.e. it increases confidence in the finding of energy/metabolic problems.

    Ron Davis presented data at the Invest in ME Conference showing that you could potentially use the Seahorse analyser to diagnose ME/CFS.

    Interestingly Ron Davis (in one of his talks - December 2017 OMF site?) said that ME/CFS did look like diabetes. Staines, at the Invest in ME Conference, said that TRIP receptors had a role in insulin regulation (diabetes). So possibly the calcium regulation (TRIP) theory Staines etc. are working on would explain the observed metabolic effects observed in ME/CFS.

    I would like to see the calcium regulation data resented at the Invest in ME Conference published.
     
  17. sea

    sea Senior Member (Voting Rights)

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    I think part of the problem is that this is a university where multiple PhD students need a novel hypothesis to research and report on and that is probably the main focus. I suspect finding answers to ME/CFS is probably a secondary goal.
     
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  18. JaimeS

    JaimeS Senior Member (Voting Rights)

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    Someone has to write the next grant -- and someone else has to approve it. Yes to the tiny PhD students trying to publish a thing -- and then moving on to the next thing, which may have nothing to do with ME.

    At least theoretically, this is all you're supposed to need to apply for an R-level grant: show the experimental design works out, and show some promising results on a limited sample size.

    I don't think Ron would mind if I pointed out that I mentioned if we called it "Type III Diabetes" that's when we'd get some real funding. ;) I was only half-joking.
     
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  19. Tom Kindlon

    Tom Kindlon Senior Member (Voting Rights)

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  20. strategist

    strategist Senior Member (Voting Rights)

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    Hi Jaime, can you tell me more about how it looks like diabetes?
     
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