Micro-RNA's in ME

[Pyrrhus]

Since 2020 brought us four new publications on micro-RNA's (miRNA), I thought I'd start a thread to collect together the various discussions on micro-RNA's.

Hopefully this will aid in the comparison of studies. Please feel free to add more studies or discussions as needed.

The basics of Micro-RNA's:

1. Normally, the cell makes messenger RNA (mRNA) which then makes proteins for the cell.
2. But sometimes, the cell makes micro-RNA (miRNA) which blocks the mRNA from making the proteins.
3. We don't fully understand why the cell makes miRNA to block its own mRNA, but it's probably just another way that the cell fine-tunes the production of proteins.
4. The cell can also "share" its micro-RNA (miRNA) with neighboring cells, in order to block neighboring cells from making certain proteins.
5. Researchers are trying to see if specific micro-RNAs (miRNA) are correlated with specific diagnoses. If they are, the correlation might lead to a diagnostic test for that diagnosis.

 

[Pyrrhus]

Cytotoxic lymphocyte microRNAs as prospective biomarkers for CFS/ME (Brenu et al., 2012)
(from the group of Staines and Marshall-Gradisnik)

Discussion:
https://forums.phoenixrising.me/threads/new-phanu-study-on-microrna-markers.17324/

Main points:

• This study looked at the micro-RNA's inside Natural Killer (NK) and CD8+ T cells of people with ME.
• Nineteen micro-RNA's were investigated.
• 9 of those micro-RNA's were decreased in NK cells.
• 1 of those micro-RNA's was decreased in CD8+ T cells.
• The authors state that these miRNAs have been associated with apoptosis, cell cycle, development and immune function.

 

[Pyrrhus]

Identification of a MicroRNA Signature for the Diagnosis of Fibromyalgia (Cerdá-Olmedo et al., 2015)
(from the group of Elisa Oltra)

Discussion:
https://forums.phoenixrising.me/thr...ture-for-the-diagnosis-of-fibromyalgia.36480/

Main points:

• The study looked at all micro-RNA's in blood cells from 11 fibromyalgia patients and 10 controls.
• The authors propose a signature of five "strikingly downregulated" micro-RNA's as a potential biomarker test for fibromyalgia.

 

[Pyrrhus]

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in ME/CFS (Almenar-Perez et al. 2020)
(from the group of Elisa Oltra)

Discussion:
https://forums.phoenixrising.me/thr...les-in-me-cfs-almenar-perez-et-al-2020.79140/

Main points:

• Blood samples of 15 severely affected ME patients and 15 healthy controls were obtained from the UK ME Biobank.
• The study looked at all micro-RNA's inside blood cells, as well as micro-RNA's inside extracellular vesicles.
• Patients appeared to have more extracellular vesicles, but of a smaller size, than controls.
• Micro-RNA’s in extracellular vesicles and inside blood cells were significantly different in ME compared to controls.
• The authors suggest that these results, in combination with related measurements, could be used as a potential biomarker test for ME.

 

[Pyrrhus]

Profile of circulating microRNAs in ME and their relation to symptom severity, and disease pathophysiology (Nepotchatykh et al., 2020)
(from the group of Alain Moreau)

Discussion:
https://forums.phoenixrising.me/thr...-disease-pathophysiology-12th-nov-2020.82009/

Main points:

• This study aimed to investigate circulating microRNA expression in severely ill ME/CFS patients before and after an innovative stress challenge that stimulates PEM.
• Their findings highlight the differential expression of eleven microRNAs associated with a physiological response to PEM.

 

[Pyrrhus]

Informatics Inference of Exercise-Induced Modulation of Brain Pathways Based on Cerebrospinal Fluid Micro-RNAs in ME/CFS (Narayan et al. 2020)
(from the group of James Baraniuk)

Discussion:
https://forums.phoenixrising.me/thr...icro-rnas-in-me-cfs-narayan-et-al-2020.83195/

Main points:

• This study looked at micro-RNA's in the cerebrospinal fluid.
• This study evaluated micro-RNA's both before and after an exercise test.
• They found that some micro-RNA's were decreased in the cerebrospinal fluid after exercise.

 

[Pyrrhus]

Unravelling ME/CFS: Gender‐specific changes in the microRNA expression profiling in ME/CFS (Cheema et al., 2020)
(from a coalition of U.S. and Spanish researchers)

Discussion:
https://forums.phoenixrising.me/thr...-profiling-in-me-cfs-cheema-et-al-2020.83184/

Main points:

• This study looked at micro-RNA's in blood cells after an exercise challenge.
• The authors note a difference in micro-RNA's based on gender.
• The authors also note a difference in micro-RNA's based on nutritional status.

 

[Judee]

The basics of Micro-RNA's:

1. Normally, the cell makes messenger RNA (mRNA) which then makes proteins for the cell.
2. But sometimes, the cell makes micro-RNA (miRNA) which blocks the mRNA from making the proteins.
3. We don't fully understand why the cell makes miRNA to block its own mRNA, but it's probably just another way that the cell fine-tunes the production of proteins.
4. The cell can also "share" its micro-RNA (miRNA) with neighboring cells, in order to block neighboring cells from making certain proteins.
5. Researchers are trying to see if specific micro-RNAs (miRNA) are correlated with specific diagnoses. If they are, the correlation might lead to a diagnostic test for that diagnosis.

Wow, you make me feel smarter. I actually think I understand all of that...at least mostly.

But that first post is as far as I got this late at night. Will go to the next one tomorrow. I don't want to overwhelm my brain cells too much.

Thanks for posting this. It also makes me feel hopeful that they will find a diagnostic test for us soon.

 

[Pyrrhus]

Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients (Blauensteiner et al., 2021)
J. Blauensteiner, R. Bertinat, L. E. León, M. Riederer, N. Sepúlveda & F. Westermeier
Published: 19 May 2021
https://www.nature.com/articles/s41598-021-89834-9

Main points:

• This study compared a few selected micro-RNA's in the blood of ME patients to that of controls.
• The study found that five micro-RNA's are increased in ME patients compared to controls.
• The authors suggest that these micro-RNA's are biomarkers for the ability of endothelial cells to release nitric oxide (NO) when necessary.

Excerpt:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by unexplained debilitating fatigue. Although the etiology is unknown, evidence supports immunological abnormalities, such as persistent inflammation and immune-cell activation, in a subset of patients.

Since the interplay between inflammation and vascular alterations is well-established in other diseases, endothelial dysfunction has emerged as another player in ME/CFS pathogenesis. Endothelial nitric oxide synthase (eNOS) generates nitric oxide (NO) that maintains endothelial homeostasis. eNOS is activated by silent information regulator 1 (Sirt1), an anti-inflammatory protein. Despite its relevance, no study has addressed the Sirt1/eNOS axis in ME/CFS.

The interest in circulating microRNAs (miRs) as potential biomarkers in ME/CFS has increased in recent years. Accordingly, we analyze a set of miRs reported to modulate the Sirt1/eNOS axis using plasma from ME/CFS patients.

Our results show that miR-21, miR-34a, miR-92a, miR-126, and miR-200c are jointly increased in ME/CFS patients compared to healthy controls. A similar finding was obtained when analyzing public miR data on peripheral blood mononuclear cells. Bioinformatics analysis shows that endothelial function-related signaling pathways are associated with these miRs, including oxidative stress and oxygen regulation. Interestingly, histone deacetylase 1, a protein responsible for epigenetic regulations, represented the most relevant node within the network.

In conclusion, our study provides a basis to find endothelial dysfunction-related biomarkers and explore novel targets in ME/CFS.

(spacing added for readability)

 

[YippeeKi YOW !!]

@Pyrrhus

Brilliant of you to make each study a separate post. All together, they would have been overwhelming, but as separate posts, they were far less intimidating ....

 

[Pyrrhus]

Diagnosis of ME/CFS With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles (González-Cebrián et al., 2022)

Discussion:
https://forums.phoenixrising.me/thr...nalysis-relevanc-gonzalez-cebrian-2022.87476/

From abstract:

A Partial Least Squares-Discriminant Analysis (PLS-DA) model initially based on 817 variables: two demographic, 34 blood analytic, 136 PBMC miRNAs, 639 Extracellular Vesicle (EV) miRNAs, and six EV features, selected an optimal number of five components, and a subset of 32 regressors showing statistically significant discriminant power. The presence of four EV-features (size and z-values of EVs prepared with or without proteinase K treatment) among the 32 regressors, suggested that blood vesicles carry relevant disease information.

From author Karl Morten on Twitter:

We can separate severe ME/CFS patients from Healthy controls with 100% accuracy.

 

[GlassCannonLife]

Good stuff @Pyrrhus! Unfortunate to see so little progress (?) in the field over the 10 years of studies though.. Hopefully it will speed up in the future..

 

[Alvin2]

From author Karl Morten on Twitter:
We can separate severe ME/CFS patients from Healthy controls with 100% accuracy.

 

[Loomcgoo]

@Pyrrhus thank you