Volunteer opportunity: Organizing Phoenix Rising articles
This section contains all the articles that have been published by Phoenix Rising over the years. As you will see if you browse here, some of the articles are outdated--either the research has been superseded or retracted or the article features an event or campaign that is now in...
Discuss the article on the Forums.

Search for biomarkers in ME/CFS using Raman spectroscopy - ME Association (UK)

Discussion in 'Latest ME/CFS Research' started by Moof, Sep 6, 2018.

  1. Moof

    Moof Senior Member

    Messages:
    215
    Likes:
    545
    UK
    FMMM1, Dolphin, percyval577 and 7 others like this.
  2. WestOzGirl

    WestOzGirl

    Messages:
    35
    Likes:
    8
    Western Australia
    Interesting. I know glyphosate’s mechanism of action in plants is the disruption of the shikimate pathway, which is involved with the synthesis of the essential aromatic amino acids, phenylalanine, tyrosine, and tryptophan. It is purported to be safe in humans because humans do not possess the shikemate pathway. However, humans are made up of more bacterial cells than our own cells.

    Early stages, but some food for thought.
     
  3. Belbyr

    Belbyr

    Messages:
    91
    Likes:
    171
    https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j#!divAbstract

    Phenylalanine can be used as a potential biomarker for diagnosis of CFS by SCRM. A machine learning classification model achieved an accuracy rate of 98% correctly assigning Raman spectra to either the CFS group or the control group. SCRM combined with machine learning algorithm therefore has the potential to become a diagnostic tool for CFS.
     
    Mary, Murph, alkt and 6 others like this.
  4. Dechi

    Dechi Senior Member

    Messages:
    1,166
    Likes:
    2,246
    I am not sure I understand this. 0 cells, what do they mean ? And what’s the date on this article ?
     
  5. ljimbo423

    ljimbo423 Senior Member

    Messages:
    1,135
    Likes:
    2,181
    United States, New Hampshire
    I don't know what 0 cells are but I found this about halfway down the page-

    link
     
    Last edited: Sep 9, 2018
    Murph, RobR, Gemini and 1 other person like this.
  6. pattismith

    pattismith Senior Member

    Messages:
    1,518
    Likes:
    2,297
    really interesting! Thanks!

    "The experimental results show that Raman bands associated with phenylalanine in 0 cells and CFS patient PBMCs were significantly higher than wild type model and healthy controls."
    "As similar changes were observed in the 0 cell model with a known deficiency in the mitochondrial respiratory chain as well as in CFS patients, our results suggest that the increase in cellular phenylalanine may relate to mitochondrial/energetic dysfunction in both systems."

    My understanding is that 0 cells is a model of mutant cells (which I'd like to know more about)

    intracellular Phenylalanine accumulation in both cells or CFS cells could be either a cause or a consequence of respiratory chain dysfunction.

    Phenylalanine accumulation is already known as a cause of dysfunction of respiratory chain:


    "The results showed a reduction of SuccinateDHase and complex I + III activity in brain cortex of rats subjected to HyperPhenylAlaninemia . We also verified that Phenylalanine inhibited the in vitro activity of complexes I + III, possibly by competition with NADH. Considering the importance of SDH and RCC for the maintenance of energy supply to brain, our results suggest that energy deficit may contribute to the Phe neurotoxicity in PhenylKetonUria (PKU)."

    "Bioenergetics

    Brain energy metabolism alterations play an important role in the pathophysiology of many inborn errors of metabolism [80-83]. In this context, energy metabolism impairment was reported in HPA animal models and patients. Significant decrease of succinate dehydrogenase (EC # 1.3.5.1) and mitochondrial respiratory chain complexes I-III activities were detected in cerebral cortex of rats subjected to experimental HPA [84], as well as decreased serum ubiquinone-10 (Coenzyme Q) concentrations in phenylketonuric patients [85]. On the other hand, Kyprianou and colleagues [86] showed no significant difference in mitochondrial respiratory chain complex I (EC # 1.6.5.3) activity in astrocytoma cells between PKU patients with or without tremor, suggesting that Phe neurotoxicity towards PKU patients does not involve the parameter of mitochondrial respiratory function. Respiratory chain complex II-III activity was also not altered in blood mononuclear cells from phenylketonuric patients [87].

    Creatine kinase (CK; EC #2.7.3.2) activity, a key enzyme for maintenance of ATP homeostasis [88], is significantly inhibited in vitro by Phe and in cerebral cortex of rats subjected to experimental HPA. These results suggest another putative pathological mechanism through which Phe induces neurometabolic alterations in PKU patients [89].

    Berti and colleagues [90] showed that bilateral administration of creatine or pyruvate into hippocampus significantly prevented the cognitive impairment triggered by Phe administration in rats in the open field apparatus, indicating that cognitive impairment found in phenylketonuric patients might be secondary to energy failure. Significant beneficial effect of creatine and pyruvate administration was confirmed by the prevention of adenylate kinase (EC # 2.7.4.3), mitochondrial and cytosolic CK activities impairment in cerebral cortex and hippocampus from pregnant and lactating rats receiving high Phe administration, corroborating the hypothesis of impaired energy metabolism on Phe neurotoxicity [91].

    Phe and its metabolites also interfere on ketone bodies metabolism through inhibition of 3-hydroxybutyrate dehydrogenase (EC # 1.1.1.30) and 3-oxo-acid CoA-transferase (EC # 2.8.3.5) activities in brain of suckling rats [92]. In addition, PPA inhibited pyruvate plus malate oxidation in human and rat skeletal muscle possible due to inhibition of pyruvate dehydrogenase complex (EC # 1.2. 4.1, EC # 2.3.1.12, EC # 1.8.1.4) activity, which could collaborate to the increased lactate levels found in PKU patients [93]. Furthermore, Phe and PPA inhibited pyruvate kinase (EC # 2.7.1.40) and hexokinase (EC # 2.7.1.1) activities in adult human and fetal brain samples [94], as well as in brain of rats submitted to HPA experimental model [95,96].

    Considering that metal ions (e.g. zinc, iron, and magnesium) are key components of metabolic enzymes [97], acting as regulatory entities on such proteins [15,98], and that they are deficient in PKU patients (as already mentioned), it cannot be ruled that the energy dysfunction observed in PKU may be ascribed to metal ion imbalances that disturb the activity of crucial enzymes of intermediary metabolism. Taken together, these data indicate that disturbances in cell bioenergetics homeostasis may contribute to Phe neurotoxicity observed in PKU."

    [​IMG]
     
    Last edited: Sep 9, 2018
    percyval577, Mary, Gemini and 2 others like this.
  7. Judee

    Judee Senior Member

    Messages:
    249
    Likes:
    495
    Wisconsin
    We need to ask one of the more scientific among us what 0 is the symbol for.
     
    Learner1 likes this.
  8. wigglethemouse

    wigglethemouse Senior Member

    Messages:
    105
    Likes:
    245
  9. pattismith

    pattismith Senior Member

    Messages:
    1,518
    Likes:
    2,297
    ok, so this is the answer to what is a 0 cell (a cell with 0 mtDNA)
    "Dr Morten and Prof Wei Huang (De artment of Engineering) from Oxford University, attempted to link mitochondrial dysfunction and ME/CFS pathogenesis by comparing the ‘fingerprint’ of a cell model containing no mitochondrial DNA (known as ‘ρ0’) to the ‘fingerprint’ of molecules from the blood cells of ME/CFS patients…"

    A Newly Established Neuronal ρ-0 Cell Line Highly Susceptible to Oxidative Stress Accumulates Iron and Other Metals

    RELEVANCE TO THE ORIGIN OF METAL ION DEPOSITS IN BRAINS WITH NEURODEGENERATIVE DISORDERS*



    Abstract
    From human neuroblastoma-derived SILA cells we have established a ρ-0 cell line that is deficient in both respiration and mitochondrial DNA. Lactate dehydrogenase activity, lactate production, and growth in the medium without glucose indicate that these cells shift from aerobic to anaerobic metabolism. Electron microscopic observations revealed abnormal mitochondria with unique cristae structures. Staining with MitoTracker dye showed that the mitochondrial transmembrane potential was reduced by 30–40% from the parent cell levels. These cells were markedly susceptible to H2O2 and died apparently by a necrotic mechanism, a process blocked by deferoxamine in the parent cells but not ρ-0 cells. Analysis by inductively coupled plasma-mass spectrometry revealed an approximately 3-fold accumulation of iron in the ρ-0 cells at confluence (n = 4–6, three clones, *p < 0.05). Iron and four other metals were all elevated in the cells of one of the ρ-0 clones and were similar to control levels in the control cybrid cells, which were replenished with normal mitochondrial DNA. Their sensitivity to H2O2 was also similar to that of the parent cells. These results indicate that a newly established neuronal related ρ-0 cell line is highly susceptible to active oxygen species and that these toxicity effects appear to be related to an accumulation of transition metals, which probably occurs through the respiratory impairment.

    Iron and other transition metals exacerbate and in some cases initiate the degeneration of neurons (e.g. 1–3) through the Fenton reaction (4). In the brain of patients with Alzheimer's disease (AD),1an increase in the content of iron (5-9) and aluminum (4, 7) has been reported, and treatment of AD patients with iron chelators has been discussed (10). In the brain of patients with Parkinson's disease and Huntington's disease, iron and other metals also appear to accumulate (8, 11). It is important to note that all of these diseases show mitochondrial abnormalities to some extent (12-19), suggesting a coupling of metal accumulation with mitochondrial deficiency. More direct evidence of mitochondrial and iron association in neurodegenerative disorders comes from an increase in mitochondrial iron in the fibroblasts of patients with Friedreich's ataxia, whose responsible gene is the mitochondrial frataxin (3, 20, 21). It would also be intriguing to uncover an association of mitochondrial respiratory deficiency and cell death with an accumulation of metals because a new, pivotal, regulatory role for mitochondria in cell survival and death has emerged from a growing body of evidence (for a review, see Ref. 22).
     
    Last edited: Sep 9, 2018
  10. Wishful

    Wishful Senior Member

    Messages:
    818
    Likes:
    1,178
    If phenylalanine was a cause of symptoms, then consuming aspartame should increase symptoms severity. I've had aspartame and notice no such effects. Of course, taking normal quantities of aspartame may not be enough to increase levels in cerebral cells significantly.
     
    alkt and pattismith like this.
  11. Belbyr

    Belbyr

    Messages:
    91
    Likes:
    171
    Even though this could be a biomarker, it might not be the cause. Just like many other illnesses...
     
    Lisa108 likes this.
  12. Lisa108

    Lisa108 Senior Member

    Messages:
    197
    Likes:
    617
    The authors of the study hypothesize that as phenylalanine was low in patient's sera and urine in previous studies,
    the elevated intracellular concentration of phenylalanine found here 'may be due to a secondary rescue mechanism (...) to maintain a normal ATP production in the metabolically dysfunctional patients' cells' (page 9 of the accepted manuscript).

    A bigger study to confirm their findings is 'under preparation' (p. 10).
     
    pattismith, Murph, Mary and 3 others like this.
  13. M Paine

    M Paine Senior Member

    Messages:
    327
    Likes:
    914
    Auckland, New Zealand
    Raman spectroscopy... mmmm... I feel like some asian noodles all of a sudden.
     
    Mary, Eve18, Lisa108 and 1 other person like this.
  14. Murph

    Murph :)

    Messages:
    944
    Likes:
    4,499
    Here's what they've published. Looks like they found high levels of one amino acid, called phenylalanine. Which is a phenomenon that occurs in a known metabolic defect.

     
    Last edited: Sep 9, 2018
    Mary, veganmua and Mel9 like this.
  15. Murph

    Murph :)

    Messages:
    944
    Likes:
    4,499
    I checked Fluge and Mella's work. They found phenylalanine levels at 95% of healthy controls in serum. This rsearch is in the cell though.

    Armstrong et al (2015)
    found a big reduction in phenyalanine in a study that looked at blood and urine.

    (That was the paper that proposed the body is using amino acids as fuel. Apparently the Phenylalanine is a clue to that. The doctor who runs the practice I go to here in Melbourne is an author on the 2015 paper, and this no doubt informed him recommending me the whey supplementation that has been so helpful to me.)
     
    Mary, pattismith, percyval577 and 3 others like this.
  16. wigglethemouse

    wigglethemouse Senior Member

    Messages:
    105
    Likes:
    245
    Given the phenyalanine finding I really enjoyed watching Chris Armstrongs Oct 2016 presentation again where he discusses this and other findings.
     
    Mary and Murph like this.
  17. Murph

    Murph :)

    Messages:
    944
    Likes:
    4,499
  18. Murph

    Murph :)

    Messages:
    944
    Likes:
    4,499
  19. Mary

    Mary Moderator

    Messages:
    4,201
    Likes:
    9,165
    Southern California
    You're right, they're the same study. This thread will be merged into this one which you noted, which was started last Thursday.

    Thanks for catching this. I just happened across your post here. A better thing to do is to hit the report button under say the initial post and that will alert the moderators that something needs attention. And then there will be a box to state the reason for the report, and you just say something like duplicate threads, need to be merged.
     
    Gemini and Murph like this.
  20. boolybooly

    boolybooly Senior Member

    Messages:
    120
    Likes:
    315
    UK
    If replicable it suggests CFS involves blood cells (PBMCs) importing phenylalanine, accumulating it internally while lowering its concentration in the plasma.

    The $64k question is ... why? Also is it just PBMCs or are other cell types doing the same?
     
    Mary and cigana like this.

See more popular forum discussions.

Share This Page