Biomolecules: Special Issue "Biomarkers in Chronic Fatigue Syndrome (ME/CFS)" (2021)

Pyrrhus

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The journal Biomolecules has started a special issue entitled "Biomarkers in Chronic Fatigue Syndrome (ME/CFS)"
https://www.mdpi.com/journal/biomolecules/special_issues/Biomarkers_in_CFS

Biomolecules said:
Guest Editor Dr. Bhupesh K. Prusty

Dear Colleagues,

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a systemic disease that affects the central nervous system, the immune system, cell energy metabolism, the autonomic nervous system, etc. The main clinical sign is persistent chronic fatigue that is not relieved by rest and lasts for more than six months. Up to 75% of patients are completely unable to work and remain wheelchair-dependent, and at least 25% are permanently housebound or even bedbound. Accordingly, the socio-economic impact of the disease is huge.

At present, no curative treatment options are available. Therefore, patients have practically no prospect of recovery or at least of returning to work. Etiological factors for ME/CFS include genetic predisposition, stress, trauma, exposure to toxins, the ratio of physical activity to rest, and a recent history of infectious disease. ME/CFS can affect individuals from all races, genders, age groups, and social statuses. The pathogenesis of ME/CFS is likely multi-factorial and various microbial and viral infections can serve as possible triggers for ME/CFS.

However, to date, no single biomarker has been identified that can be generalized to the entire patient population. Considering the heterogeneity of ME/CFS, it is plausible that a specific set of biomarkers might enable us to define disease subtypes. Identification of biomarkers will allow for prognosis of the disease’s development and promote the development of a specific definition for diagnostics and a treatment plan. Hence, I encourage researchers from diverse backgrounds (clinics, systems medicine, genetics, molecular biology, epidemiology) to contribute original research and review articles on any aspect of biomarker identification, biomarker characterization, or translational approaches of clinical relevance to this Special Issue, which aims to bring ideas from different fields of science to one common platform that may stimulate further research and solve a modern day clinical mystery.

Dr. Bhupesh K. Prusty
Guest Editor
(spacing added for readability)
 
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Pyrrhus

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Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study (Fernandez Guerra et al., 2021)
https://www.mdpi.com/2218-273X/11/7/961

Excerpt:
Fernandez et al 2021 said:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction.

Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls. We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being.

This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels. Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.
 

Pyrrhus

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I'm confused- is this an issue that has yet to come out?

We heard about this last winter from Dr. Prusty I seem to recall.
The first paper in this issue has just been published.

I believe they will be accepting submissions for more papers through September.

Since everyone wants their paper published as soon as possible, it appears that publishers no longer wait until they have a full issue to begin publishing the papers.
 

pattismith

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Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study (Fernandez Guerra et al., 2021)
https://www.mdpi.com/2218-273X/11/7/961

Excerpt:

PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels.
does it mean they found PDH inhibition in PBMC?

Did they check lactates in blood?
I suppose that if PDH was inhibited in other cells and especially in muscles, we should have hyperlactatemia.

Some acquired PDH inhibition are known to occur

-Thiamine deficiency
-sepsis (endotoxines)
-cytokines (TNF alpha, IL-1alpha)
-fungal toxines, pesticides
-arsenic


PDH is also inhibited by the products of its activity by negative feedback (acetyl coA, NADH, ATP)


RMS_idPAS_D_ISBN_pu2013-43s_sa05_art05.pdf (revmed.ch)

(PDF) Inhibition of pyruvate dehydrogenase complex by moniliformin (researchgate.net)

Chronic toxic effects of the carbamate pesticide sevin on carbohydrate metabolism in a freshwater snakehead fish, Channa punctatus - ScienceDirect
 

pattismith

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According to the graphical abstract, it looks like that is what they are saying:

Interestingly, reduced activation of the PDH has been reported in other studies, but by upregulation of the PDH kinase instead of downregulation of the PDH phosphatase [29]. Recent studies in muscle cells from ME/CFS patients point to a PDH dysfunction as a potential cause of mitochondrial dysfunction [67].
Here the 2020 study cited, showing the same issue in muscle as in immune cells:

Substrate utilisation of cultured skeletal muscle cells in patients with CFS | Scientific Reports (nature.com)
 

junkcrap50

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Interestingly, reduced activation of the PDH has been reported in other studies, but by upregulation of the PDH kinase instead of downregulation of the PDH phosphatase [29].
Can those two findings be compared like that and conclude different causations when used different measurement techniques, looking at different things?

Fluge et al study method used amino acid and mRNA analysis. Fluge et al found "increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells." The Tomas et al study method used "extracellular flux analysis and proteomics." Tomas et al study found "a significantly decreased level of PDPR."
 
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The journal Biomolecules has started a special issue entitled "Biomarkers in Chronic Fatigue Syndrome (ME/CFS)"
https://www.mdpi.com/journal/biomolecules/special_issues/Biomarkers_in_CFS
the paper above concludes that dichloroacetate (DCA) may work to reduce these symptoms in about 30-40 % of the patients (cites two 2018 pilot trials).

https://pubmed.ncbi.nlm.nih.gov/29602463/

This paper:

https://pubmed.ncbi.nlm.nih.gov/30220343/

discusses differences between responders and non responders relative to DCA....

Its only the abstract. So I wonder what these differences are?

(I have 3 jars of DCA in the cabinet, purchased for COVID avoidance, at great expense).
 
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You can download the full paper, in PDF form here.
thank you.....

I have read thru this info and determined I am unable to make sense out of this. I will hope for greater clarity some other day. I did actually try.

It does seem odd there seem to be so few who have tried this substance that might work in 30-40% of us.

I don't experiment well, so I understand why i have yet to try it. Where are the DCA experimenters?
 

Pyrrhus

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Potential of Activin B as a Clinical Biomarker in ME/CFS (Gravelsina et al., 2021)
https://www.mdpi.com/2218-273X/11/8/1189

Excerpt:
Gravelsina et al 2021 said:
Reliable serum biomarkers are of immense need for diagnostic purposes of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—a disabling and complex disease for which diagnosis is mainly based on clinical symptoms.

The aim of this study was to evaluate a possible diagnostic potential of activin B by directly comparing 134 cases of ME/CFS with 54 healthy controls. Analyses of human activin B level in plasma samples were performed using a validated human activin B ELISA assay.

The results of the study show that activin B levels did not differ statistically significantly between ME/CFS patients and healthy controls (p = 0.6511). No gender or age-related differences in activin B levels were observed in the ME/CFS group and healthy controls. The level of activin B tended to decrease with increasing visual analogue scale score (r = −0.2004; p = 0.5085) nevertheless the results obtained so far does not support the clinical utility of activin B as a biomarker for ME/CFS.