Two old OMF ideas are progressing: nanoneedle and RBC deformability.

[Murph]

1. Money is flowing in the UK for some researchers to detect electrical impedance from ME/CFS white blood cells and see what is causing it. This picks up the old "nano-needle" research that appeared to fizzle out when Efsandyarpour left Ron's lab.
https://www.meresearch.org.uk/me-re...-aims-to-create-a-diagnostic-test-for-me-cfs/

What's good here is they're not using some fragile bespoke technology. The link says:

The UK researchers have already used a more robust approach to identify statistically significant differences between the electrical properties in blood from people with ME/CFS compared to healthy and multiple sclerosis (MS) controls (using samples from the UK ME/CFS Biobank).

2. UC Davis is studying red blood cell deformability and has not only confirmed it is worse in mecfs patients, they have also started looking at drugs that fix the problem. This comes from the recent NIH webinar on circulation, around the 2h44min mark.
The slide shows that before any drugs are brought in rbc velocity doesn't change much in mecfs patients even when oxygen levels change (they should!). This can be fixed using xanomeline, which hits muscarinic receptors and is likely to be fda approved later this year (for schizophrenia, in a combination drug format).

It's wonderful to see ideas you thought were done for being actually explored. The new post-covid environment of money and energy is working so much better for us than the pre-2020 situation.

 

[datadragon]

Hi @Murph. What davis put out in 2018 said Taken together, this data shows that RBCs from ME/CFS patients have reduced deformability. Taken together, our data demonstrates that the significant decrease in deformability of RBCs from ME/CFS patients may have origins in oxidative stress, and suggests that altered microvascular perfusion can be a possible cause for ME/CFS symptoms. Link

So I took a look: Of note, both of NF-κB and NLRP3 inflammasome persuade asymmetry of erythrocyte membrane with decrease of erythrocyte deformability in normal and sickle erythrocytes. The release of pro-inflammatory cytokines via activation of the nuclear factor kappa B (NF-κB) and nod-like receptor pyrin 3 (NLRP3) inflammasomes both contribute to increased blood viscosity. Increased pro-inflammatory cytokines promote elevation of blood viscosity in part by inducing expression of fibrinogen with a reduction of erythrocyte deformability.
https://pubmed.ncbi.nlm.nih.gov/33145778
https://pubmed.ncbi.nlm.nih.gov/32231672/

The activation of the NF-κB pathway by ROS not only mediates the assembly of the NLRP3 inflammasome but also directly promotes the expression of tumor necrosis factor-α (TNF-α), pro-IL-1β, IL-6, and other inflammatory factors
https://cmbl.biomedcentral.com/articles/10.1186/s11658-023-00462-9
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00085/full

The Zinc Finger Protein Gfi1 Controls TLR4-Mediated Inflammatory Response by Directly Antagonizing NF-κB Transcription Factor
https://www.sciencedirect.com/science/article/pii/S0006497119477677

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Zinc inhibits iNOS-dependent nitrite accumulation in endothelial cells. Zinc decreases cytokine-induced iNOS expression in endothelial cells. Zinc inhibits iNOS promoter activity. NF-kB silencing abolishes cytokine-induced iNOS expression. Zinc inhibits the transactivation activity of NFκB. https://www.sciencedirect.com/science/article/pii/S2213231714000834 from: https://forums.phoenixrising.me/threads/is-there-bh4-supplement-medicine.22480/post-2452006

Interferon-y (intensive exercise also is ifn-y), Interferon-α (IFN-a) and inflammatory cytokines IL-1β, IL-6 and TNF-a, have all been shown to induce metallothioneins in the research, which can all reduce zinc availability and then further reduce its uptake/absorption in the gut. NLRP3 activation also leads to IL-1b (and Il-6) and IL-18. Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma (IFN-y) production, and expansion of natural killer cells.
https://forums.phoenixrising.me/threads/eating-sweets-exhausts-me.91481/post-2452529

 

[Murph]

Hi @Murph. What davis put out in 2018 said Taken together, this data shows that RBCs from ME/CFS patients have reduced deformability. Taken together, our data demonstrates that the significant decrease in deformability of RBCs from ME/CFS patients may have origins in oxidative stress, and suggests that altered microvascular perfusion can be a possible cause for ME/CFS symptoms. Link

So I took a look: Of note, both of NF-κB and NLRP3 inflammasome persuade asymmetry of erythrocyte membrane with decrease of erythrocyte deformability in normal and sickle erythrocytes. The release of pro-inflammatory cytokines via activation of the nuclear factor kappa B (NF-κB) and nod-like receptor pyrin 3 (NLRP3) inflammasomes both contribute to increased blood viscosity. Increased pro-inflammatory cytokines promote elevation of blood viscosity in part by inducing expression of fibrinogen with a reduction of erythrocyte deformability.
https://pubmed.ncbi.nlm.nih.gov/33145778
https://pubmed.ncbi.nlm.nih.gov/32231672/

The activation of the NF-κB pathway by ROS not only mediates the assembly of the NLRP3 inflammasome but also directly promotes the expression of tumor necrosis factor-α (TNF-α), pro-IL-1β, IL-6, and other inflammatory factors
https://cmbl.biomedcentral.com/articles/10.1186/s11658-023-00462-9
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00085/full

The Zinc Finger Protein Gfi1 Controls TLR4-Mediated Inflammatory Response by Directly Antagonizing NF-κB Transcription Factor
https://www.sciencedirect.com/science/article/pii/S0006497119477677

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Zinc inhibits iNOS-dependent nitrite accumulation in endothelial cells. Zinc decreases cytokine-induced iNOS expression in endothelial cells. Zinc inhibits iNOS promoter activity. NF-kB silencing abolishes cytokine-induced iNOS expression. Zinc inhibits the transactivation activity of NFκB. https://www.sciencedirect.com/science/article/pii/S2213231714000834 from: https://forums.phoenixrising.me/threads/is-there-bh4-supplement-medicine.22480/post-2452006

Interferon-y (intensive exercise also is ifn-y), Interferon-α (IFN-a) and inflammatory cytokines IL-1β, IL-6 and TNF-a, have all been shown to induce metallothioneins in the research, which can all reduce zinc availability and then further reduce its uptake/absorption in the gut. NLRP3 activation also leads to IL-1b (and Il-6) and IL-18. Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma (IFN-y) production, and expansion of natural killer cells.
https://forums.phoenixrising.me/threads/eating-sweets-exhausts-me.91481/post-2452529

All roads lead to zinc for you.

I remember when I was the same with mTor. If a molecule is well studied and has many roles in the body you can find references to it in relation to any biological process, and vivid descriptions of what problems its failures can cause. Researchers love to describe things as "a key regulator of". This can create confirmation bias - whenever anything comes up you can find a paper that links the new thing to your pet idea.

I'm not saying it's not zinc. but i am saying that some meta-cognition might help you think about whether zinc is profoundly involved in mecfs or just profoundly involved in biological processes.