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Dysregulation of extracellular vesicle protein cargo in female ME/CFS cases & sedentary controls in response to maximal exercise, 2023 Giloteaux et al

Discussion in 'ME/CFS research' started by Andy, Aug 30, 2023.

  1. Andy

    Andy Committee Member

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    Preprint. Now published - see post #18

    This is from Maureen Hanson's group.

    Abstract

    In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue, and reduces risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance.

    We hypothesized that altered extracellular vesicle (EV) signaling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 minutes, and 24 hours after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics.

    The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients vs. controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system, and brain signaling.

    https://www.biorxiv.org/content/10.1101/2023.08.28.555033v1
     
    Last edited by a moderator: Jan 5, 2024
  2. mariovitali

    mariovitali Senior Member (Voting Rights)

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    alktipping and Ash like this.
  3. Ash

    Ash Senior Member (Voting Rights)

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  4. mariovitali

    mariovitali Senior Member (Voting Rights)

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    I am describing one more example on how advanced analytical techniques (available since 2015) have been outperforming findings from conventional researchers. LXR (Liver X receptor) is the latest example which was identified as being important in 2017 by a method called Network Analysis in the link I provided.

    Also you can see on the second snapshot that LXR/RXR activation were significantly inhibited 24 hours post-exercise.
     
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  5. Ash

    Ash Senior Member (Voting Rights)

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    Thanks @mariovitali!

    I wasn’t able to read the paper at top of thread due to exhaustion and was trying to work out if it’s findings were promising or not from the comments section.
     
    alktipping, Binkie4 and mariovitali like this.
  6. mariovitali

    mariovitali Senior Member (Voting Rights)

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    For the record, I believe that what Dr hanson found is related to impaired apoptotic cell clearance. I submit 2 slides from a presentation I made in 2018. Observe where LXR/RXR is situated in the graphs : Screen Shot 2023-08-30 at 16.06.56.png

    LXR Prezzo1.png
     
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  7. rvallee

    rvallee Senior Member (Voting Rights)

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    This is far above my meager understanding of biology. Which I like. It's so unimpressive looking at BPS "research" and it's basically high school level, both the study and the paper.

    Took a few screenshots of some key results:

     
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  8. Fizzlou

    Fizzlou Senior Member (Voting Rights)

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  9. DMissa

    DMissa Established Member (Voting Rights)

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    A text mining model once pointed at one thing (amongst many things), that also popped up in this study (as one of many things) and this coincidence strengthens your belief in besmirching biologists?
     
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  10. Hutan

    Hutan Moderator Staff Member

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    There's a nice summary of work done on EVs in ME/CFS in the paper:

    Eguchi study link: Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers...ME/CFS 2019, Eguchi et al. Edit - having just read through the thread for that study, the conclusions on EV proteins in the Eguchi study were based on very small samples.

    I think work on difference in the numbers and size of EVs is less interesting than what is actually in the EVs - possibly numbers and size are affected by exercise. It sounds from this as though only one study so far has looked at proteins in the EVs (the Eguchi study). This Giloteaux study looks at the effect of an exercise challenge, which is great. Also great to have a replication of the Eguchi study.
     
    Last edited: Aug 31, 2023
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  11. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    From first read through, I would say the findings are likely valid and useful. Others may have an opinion on methodological weaknesses that I haven't realised though.

    I hope the next paper in the series will be looking at the microRNA content of EVs, similar to Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in ME/CFS (2020)
     
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  12. DMissa

    DMissa Established Member (Voting Rights)

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    Okay having read it this is a cool paper. We have EV people in the building where I work, if I find money for it, it could be a fun side project to see how EV proteomes from patient primary cells or cell lines compare to a) whole cell proteomes and b) the published plasma EV proteomes.
     
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  13. mariovitali

    mariovitali Senior Member (Voting Rights)

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    The following have been identified before conventional research using Artificial Intelligence methods : pyruvate dehydrogenase complex, phospholipid metabolism dysregulation, peroxisomal dysfunction,bile acid metabolism dysregulation, endoplasmic reticulum stress (latest NIH study),LXR (there may be more, I will have to go thhrough the results)

    If you consider how many millions of possible concepts exist in medicine and also that there was no help from biologists, I would say that this is quite good for a result.
     
    Last edited: Aug 31, 2023
    obeat, Fizzlou and Sean like this.
  14. Hutan

    Hutan Moderator Staff Member

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    There's lots to think about in this paper.

    One is how variable exosome contents are before, during and after exercise (see Figure 5). It means that any study of them has to really carefully control for exertion. I wonder how long exosomes last and if there is variation diurnally and also with menstrual cycle.

    I wonder if cognitive exertion (as opposed to physical exertion) affects exosome composition - I'd love to see a study of that.

    It's interesting to look at the pathways that are upregulated or down regulated in ME/CFS compared to the controls - many normalise straight after exercise, but then either revert to the baseline level of abnormality or become even more abnormal. Those ones that become more abnormal might tell us something about PEM, pathways like
    LXR/RXR Activation (down)
    RHOGDI Signalling (down)
    PAK signalling (up)
    RAC signalling (up)
    Ephrin receptor signalling (up)​

    as well as those that become very different immediately after exercise that might cause some downstream impact on cells, pathways like
    coagulation system (down)
    acute phase response signalling (down)
    ERK5 signalling (up)
    14-3-3 mediated signalling (up)
    actin cytoskeleton signalling (down)
    RHOA signalling (down)​


    Figure 5
    Screen Shot 2023-08-31 at 6.41.42 pm.png
     
    Last edited: Aug 31, 2023
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  15. mariovitali

    mariovitali Senior Member (Voting Rights)

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    @Hutan I think we need better enrichment analysis . Phagocytosis should be among the results and also apoptotic cell clearance
     
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  16. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    I'm uncertain whether this might relate, but just to note that freely circulating FN1 was high in serum in Prusty's preprint (and IgM-FN1 was low), and that HSPA5 is aka Binding immunoglobulin protein (BiP) aka 78 kDa glucose-regulated protein (GRP-78). BiP was abnormally low in the recent WASF3 paper, when it should be upregulated in response to ER stress.
     
    Last edited: Aug 31, 2023
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  17. mariovitali

    mariovitali Senior Member (Voting Rights)

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    I just realised something regarding RHOGDI. RHOGDI is associated according to Wikipedia with RhOA :

    https://en.wikipedia.org/wiki/Low-affinity_nerve_growth_factor_receptor#RhoGDI_and_RhoA


    Now observe the following slide and you will see RhoA-GTP along with LXR/RXR.Also, next to the red annotation (on the left) you can see TSP-1 , this is Thrombospondin which OMF is looking at :


    https://www.omf.ngo/study-of-thrombospondin-1/


    We also have the following post where C1Q is mentioned from a spanish study :

    https://mecfsskeptic.com/2021-looking-back-at-a-year-of-me-cfs-research/


    It gets more interesting : Next to the red annotation we read MFGE8 also known as Lactadherin. Lactadherin could be ibvestigated for its use in order to avoid fibrin formation :

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794502/


    Could all of this be a coincidence?


    [​IMG]
     
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  18. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Published as —

    Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise
    Ludovic Giloteaux; Katherine A. Glass; Arnaud Germain; Carl J. Franconi; Sheng Zhang; Maureen R. Hanson

    In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise).

    EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 min, and 24 h after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics.

    The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients versus controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system and brain signalling.

    Link | PDF (Journal of Extracellular Vesicles)
     
  19. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Increased clusterin abundance post-exercise positively correlates with pain and fatigue

     
    obeat, Michelle, MeSci and 3 others like this.
  20. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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