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Presentation at EUROMENE, London UK

On September 13th, 2018 i had the opportunity to present to Members of the EUROMENE Group for 60 minutes the hypothesis on specific mechanisms behind ME/CFS and several other Syndromes such as Post-Finasteride Syndrome, Post-Accutane Syndrome and more.

Before continuing i would like to Thank Professor Modra Murovska for giving me the opportunity to present this work for which advanced analytical techniques (Machine Learning , Network Analysis, Natural Language Processing / Understanding) were been used since 2011.  I would also like to thank Dr Luis Nacul and everyone at the CureME Team at London School of Hygiene and Tropical Medicine for their hard work, commitment and for being such great hosts.

The presentation consisted of 71 slides and since i have many requests from -mainly- ME/CFS Patients to present this hypothesis in a simplistic way, i decided to write this post.

Here are the main elements of the hypothesis. Please note that it is not suggested that the following holds for…
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The multiple roles of PTPN11

It is time to look at Gene named PTPN11 (also known as SHP-2), Tyrosine-Protein Phosphatase non-receptor type 11. Network Analysis suggests that it may have an important role to the syndromes discussed in this Blog so it is time to hypothesize why this is so.
As previously discussed, the techniques being used have identified specific Pathways / Biological functions and Conditions that require further investigation. These are :
-Vitamin K metabolism -Bile Acid Metabolism -Phagocytosis/Endocytosis -Endoplasmic Reticulum (ER) Stress -Liver Disease -Gut Dysbiosis
According to [1], PTPN11/SHP-2 coordinates Carbohydrate, Lipid and  Bile Acid synthesis in the Liver and Pancreas as well as Gut Dysbiosis.
As also stated in [2] :
"The Shp2hep−/− mice exhibited early onset hepatobiliary defects, including enlarged gallbladder, elevation of systemic BA levels, and ductal cell proliferation (Figures 1 and 3). Furthermore, Shp2hep−/− animals were more susceptible to biliary obstruction (Figur…

Gut Microbiome, Bile Acids and Butyric Acid

As previously discussed, Machine Learning and Network Analysis have suggested the possible role of Bile Acids in ME/CFS and several other syndromes such as Post-Finasteride Syndrome, Post-Accutane Syndrome and Gulf War Ilness Syndrome .
It is time to look at one more reason on why Bile Acid metabolism and Liver pathology (e.g Hemochromatosis, WIlson's Disease, Gilbert's Syndrome) should be further investigated :

The reason is the association of Bile Acids (BAs) with the Gut Microbiome.

As discussed in [1] :

"the gut microbiota closely interact and modulate each other; BAs exert direct control on the intestinal microbiota. By binding to FXR, they induce production of antimicrobial peptides (AMPs) such as angiogenin 1 and RNase family member 4, which are directly involved in inhibiting gut microbial overgrowth and subsequent gut barrier dysfunction"

Professors Derya Unutmaz (Jackson laboratories) and W. Ian Lipkin (Columbia University) are investigating the importance…

Milk Fat Globule-EGF Factor 8 and MFGM

Moving forward to Medical Topics most likely related to ME/CFS and all syndromes discussed in the first post of this blog, it is now time to focus on Milk-Fat Globule Membrane (MFGM), Gene name MFGE8.

According to Wikipedia [1] :

Milk fat globule membrane (MFGM) is a complex and unique structure composed primarily of lipids and proteins that surrounds milk fat globule secreted from the milk producing cells of humans and other mammals. It is a source of multiple bioactive compounds, including phospholipids, glycolipids, glycoproteins, and carbohydrates that have important functional roles within the brain and gut.
Machine Learning suggests a very high importance of Milk-Fat Globule Membrane and MFGE8. I believe there are a number of reasons for this. It appears that MFGE8  has several positive qualities that are beneficial for Phagocytosis and apoptotic cell clearance, Inflammation, Autoimmunity and Intestinal Barrier Integrity to name a few. Here are some excerpts from [2,3] :

Extracellular Vesicles

It was quite interesting to see more from the work of Maureen Hanson , Professor at University of Cornell [1]. In her Webpage -at the moment of Writing- Extracellular Vesicles (EVs) are being mentioned as one of her Current Research projects. More specifically it is stated that :
"Another project aims to identify differences in gene expression and cargo of extracellular vesicles at baseline and following exercise in healthy and in subjects diagnosed with ME/CFS"

I will visit EVs later in the post.

 A paper of great interest by Professor Hanson is [2]. In this paper we read the following :

"Primary bile acids such as sulfoglycolithocholate (13) are synthesized in the liver and the major bile salts result from its conjugation with taurine (28) and glycine, forming taurochenodeoxycholate and glycochenodeoxycholate (21), respectively, which are all numbered metabolites found to be significantly reduced in ME/CFS patients. Reduction in these compounds is suggestive of damage …

Latest Network Analysis Results

I would like now to present the latest results as these where found using Network Analysis. The Network Analysis graph that has been presented so far was generated on April 2017. Since then many more topics were added and considered using both Network Analysis and Machine Learning Techniques.
Before continuing, please read the following Disclaimer :

The information discussed in this Blog and this Post is purely informational and does not constitute any Medical Advice of any Kind. If you are a patient do not take any chances with your Health. Talk to a Certified Health Professional.

The Network Analysis Graph (of which a specific area is shown) looks as follows :

From the Network Analysis we may hypothesise the following :

-The potentially  important roles of NAD (Nicotinamide Adenine Dinucleotide)  and Tocotrienol. The reason for which Tocotrienol is considered important requires further Research.
-The central roles of Flavoproteins and particularly FMN (Flavin Mononucleotide)
-The impor…