Extracellular Vesicles in ME

[Consul]

I think Prusty says there is upregulated igM in patients to compensate for dysfunctional complement system. Maybe CAMP is upregulated for the same reason.

 

[Osaca]

The Charite are conducting a study on extracellular vesicles in ME/CFS. Their goal is to find a potential biomarker of endothelial dysfunction in ME/CFS. The study is lead by Martina Seifert (yay, a new researcher with ME/CFS interest!). The study is funded by the German association of ME/CFS. See here for more info: https://www.mecfs.de/forschungsfoerderung-2022/.

 

[Consul]

New preprint from Maureen Hanson

https://www.biorxiv.org/content/10.1101/2023.08.28.555033v1

 

[mariovitali]

LXR (discussed in the paper) has been identified since 2017 (second image)



https://forums.phoenixrising.me/threads/machine-learning-assisted-research-on-cfs.51283/

 

[Osaca]

Could you please provide some additional information? Quoting one of the many thing that appears in one of the many different studies and linking it to something without any pathobiological relations or understanding gives me absolutely no additional knowledge. Does LXR appears in your algorithm since you place a focus on the liver or are the conclusions far more involved? I read through your older threads and saw that you managed to set up a collaboration with researchers, is that still running?

 

[Violeta]

Some info about LXR. I do not know if Maureen Hanson's info includes anything from this study.

LXR Alpha Restricts Gammaherpesvirus Reactivation from Latently Infected Peritoneal Cells​

Liver X receptors (LXRs) are nuclear receptors that mediate cholesterol and fatty acid homeostasis. Importantly, as ligand-activated transcription factors, LXRs represent potential targets for the treatment of hypercholesterolemia and atherosclerosis. Here, we demonstrate that LXRα, one of the two LXR isoforms, restricts reactivation of latent gammaherpesvirus from peritoneal cells. As gammaherpesviruses are ubiquitous oncogenic agents, LXRs may represent a targetable host factor for the treatment of poorly controlled gammaherpesvirus infection and associated lymphomagenesis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401431/

You can see LXR and RXR at the bottom of the mevalonate pathway. I don't know exactly what that infers yet.

 

[Violeta]

This article is more helpful for basics.

Ligands of Therapeutic Utility for the Liver X Receptors​

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions.

https://www.mdpi.com/1420-3049/22/1/88

 

[Violeta]

"These data provide mechanistic details on LXR and PPARδ activation in efferocytotic human macrophages."

"While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material."

Is this not happening? Why not?

​

Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages​

https://pubmed.ncbi.nlm.nih.gov/34025647/

 

[mariovitali]

@Violeta As discussed on my Twitter thread, the system suggests that LXR along with Phagocytosis, apoptotic cell clearance and possibly ABCA1 should be looked at.

Could you please provide some additional information? Quoting one of the many thing that appears in one of the many different studies and linking it to something without any pathobiological relations or understanding gives me absolutely no additional knowledge. Does LXR appears in your algorithm since you place a focus on the liver or are the conclusions far more involved? I read through your older threads

@Osaca For the record , Artificial Intelligence methods have identified many medical concepts as being important prior any work by humans.

Regarding your question : I am not a medical researcher so I cannot answer your question unfortunately. The tool identifies certain associations (see my answer to @Violeta earlier in this post. It is the experts that need to give potential explanations and mechanisms as they have the necessary knowledge to do so.