California Dreaming - Why would an Endotoxin and Brain Disease Expert fail to mention the known Amyloid Fibrin Catalyst in the Journal Nature ?
Lead authors in Nature papers are usually positioned because they made a major contribution to the work. Then we check for supervising authors conflicts of interest and flawed methodology.
Many have written about a recent paper in Nature1 here on Substack.
The paper by Jae Kyu Ryu et al. claims to show that Fibrin drives thromboinflammation and neuropathology in COVID-19.
I found that quite interesting until I downloaded the article, quickly skimmed through and spotted major problems. For example, I responded to my friend Moriarty2 thus:
As I said with some relevant references I have subsequently tagged,
the paper by Ryu et al. should not have been published in its present form because it fails to reference, in relation to Blood Clots, endotoxin, lps or lipopolysaccharide and the effects that would have if present.
They say "Recombinant spike was produced by transient transfection in CHO (Chinese Hamster Ovary) cells by Celltheon. Spike was purified by Ni2+-NTA affinity chromatography, eluted in phosphate-buffered saline (PBS) containing imidazole, buffer exchanged into 1× PBS and purified by size-exclusion chromatography (Superdex 200 column)."
Resia Pretorius3 only gets a passing mention at reference 23.
The authors also fail to mention the work of Ganna Petruk.4
Nickel contamination a possibility
Ni2+-NTA affinity chromatography runs the risk of Nickel contamination of the Recombinant spike.5
Readers will recall that Nickel attacks the same receptors as Endotoxin, causing thromboinflammation and neuropathology including Stroke.6
Apart from the Nickel problem, affinity chromatography tends to be non-specific, allowing other macromolecules through.
Jae Kyu Ryu the Endotoxin Expert
Back to lead author of what is now being called the “California Study” in some circles, especially devotees of “Spikeopathy”.
In 2002, while working in Canada, he investigated Endotoxin damage to Human Microglia and worked on drugs that might ameliorate the effects and clarified some of the pathways involved.7
In 2007 he was looking at Endotoxin induced Microglial Activation and Neuronal Damage in Inflamed Brain in Rats.8
In 2012, while working in Canada, he demonstrated that microglial activation with chronic peripheral Endotoxin challenge “was paralleled with vascular remodeling including dilatation, increased vessel wall thickness, increased Blood Brain Barrier (BBB) permeability and Fibrinogen deposition in YAC128 Mice.9 He used a dose of 1 mg/kg once per week from 8 months of age until the mice were sacrificed at 12 months of age one week post Endotoxin (LPS) injection.
In 2014 he was investigating Neuroinflammation after Tibia Fracture and Endotoxemia in Mice.10
Of course this list is not exhaustive.
Declared Interests
The “California Study” quite properly includes this section.
K.A. is listed as an inventor on US patents 7,807,645, 8,569,242, 8,877,195and 8,980,836, covering fibrin antibodies, submitted by the University of California. K.A. and J.K.R. are listed as co-inventors on US patent 9,669,112 covering fibrin in vivo models, and US patents 10,451,611 and 11,573,222 covering in vitro fibrin assays submitted by Gladstone Institutes. K.A., J.K.R., M.M. and W.C.G. are listed as co-inventors on US patent 12,016,934 covering the COVID-induced thromboinflammation model and US patent application 18/267,710 for use of fibrin immunotherapy in COVID-19 submitted by Gladstone Institutes. K.A. is a co-founder and scientific advisor of Therini Bio. K.A. has served as a consultant for F. Hoffman-La Roche not related to this study. W.C.G. is a co-founder and shareholder in InvisiShield Technologies, but work in this company has no overlap with the topic or findings presented in this paper. M.O. is a founder of DirectBio and is on the scientific advisory board of InvisiShield, but both are scientifically unrelated to this study. The Krogan Laboratory has received research support from Vir Biotechnology, F. Hoffmann-La Roche and Rezo Therapeutics unrelated to this study. N.J.K. has a financially compensated consulting agreement with Maze Therapeutics, is the president and is on the board of directors of Rezo Therapeutics, and is a shareholder in Tenaya Therapeutics, Maze Therapeutics, Rezo Therapeutics, GEn1E Lifesciences and Interline Therapeutics, but all are unrelated to this study. Their interests are managed in accordance with their respective institutions’ conflict of interest policies. The other authors declare no competing interests.
See also the interesting coverage by an anonymous Substacker.11
Conclusion
Jae Kyu Ryu the Endotoxin Expert has demonstrated over 20 years of research related to various Brain Diseases and I stand by my comments re serious omissions and probable confounders in this latest paper.
Email length limit reached. Please tell me about other critiques.
Jae Kyu Ryu, Zhaoqi Yan, Mauricio Montano, Elif G. Sozmen, Karuna Dixit, RahulK. Suryawanshi, Yusuke Matsui, Ekram Helmy, Prashant Kaushal, Sara K. Makanani, Thomas J. Deerinck, Anke Meyer-Franke, Pamela E. Rios Coronado, Troy N. Trevino, Min-Gyoung Shin, Reshmi Tognatta, Yixin Liu, Renaud Schuck, Lucas Le, Hisao Miyajima, Andrew S. Mendiola, Nikhita Arun, Brandon Guo, Taha Y. Taha, Ayushi Agrawal, Eilidh MacDonald, Oliver Aries, Aaron Yan, Olivia Weaver, Mark A. Petersen, Rosa Meza Acevedo, MariadelPilar S. Alzamora, Reuben Thomas, Michela Traglia, Valentina L. Kouznetsova, Igor F. Tsigelny, Alexander R. Pico, Kristy Red-Horse, Mark H. Ellisman, NevanJ. Krogan, Mehdi Bouhaddou, Melanie Ott, Warner C. Greene, and Katerina Akassoglou. 28 August 2024. Fibrin drives thromboinflammation and neuropathology in COVID-19. https://www.nature.com/articles/s41586-024-07873-4
Joshua A. Bornhorst and Joseph J. Falke. 2010. Purification of Proteins Using Polyhistidine Affinity Tags. https://www.sciencedirect.com/science/article/abs/pii/S0076687900260588
Hyan B Choi , C Khoo, Jae K Ryu, Edo van Breemen, Seung U Kim, James G McLarnon. 2002. Inhibition of lipopolysaccharide-induced cyclooxygenase-2, tumor necrosis factor-α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195. https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1471-4159.2002.01122.x
Hyun B. Choi, Jae K. Ryu, Seung U. Kim and James G. McLarnon. 2007. Modulation of the Purinergic P2X7 Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain. https://www.jneurosci.org/content/27/18/4957.long
Sonia Franciosi, Jae K. Ryu, Yaein Shim, Austin Hill, Colum Connolly, Michael R. Hayden, James G. McLarnon, Blair R. Leavitt. 2012. Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease. Neurobiology of Disease 45:438-449.
Niccolò Terrando, Ting Yang, Jae Kyu Ryu, Phillip T. Newton, Claudia Monaco, Marc Feldmann, Daqing Ma, Katerina Akassoglou and Mervyn Maze. 2014. Stimulation of the α7 Nicotinic Acetylcholine Receptor Protects against Neuroinflammation after Tibia Fracture and Endotoxemia in Mice. https://molmed.biomedcentral.com/articles/10.2119/molmed.2014.00143
I can't comment on the details of this article and prior research. Here is a slightly improved version of what I wrote about this article in a comment at: https://petermcculloughmd.substack.com/p/most-variation-in-all-cause-mortality/comment/67438047. This concerns the article's dismissive approach to the possibility that the spike replica proteins the body produces in response to mRNA and adenovirus vector so-called "vaccines" would also interact with fibrin and so cause excessive clotting AKA coagulopathy.
An article which I haven't seen discussed much is Ryu et al. 2024-08-28 "Fibrin drives thromboinflammation and neuropathology in COVID-19" https://www.nature.com/articles/s41586-024-07873-4.
"Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection."
The mRNA and adenovirus vector gene-therapy injections falsely marketed as "vaccines" cause a massive cellular production of proteins closely modeled on SARS-CoV-2 spike proteins. The amount of such spike proteins produced is surely massive compared to most or perhaps all infections, since the mRNA or adenoviruses program cells all over the body to produce these proteins, many of which would go into circulation, with the remainder bound to the outside of their cell membrane until the immune system destroys these cell. The immune system can't do anything else to stop the production of these spike proteins.
There's every reason to believe that these gene-therapy-produced spike proteins, free-moving and bound to cells' plasma membranes, would have the same interactions with fibrin, so causing excessive coagulation and so clots. However, the authors deny this:
"In general, COVID-19 RNA vaccines lead to small amounts of spike protein accumulating locally and within draining lymph nodes where the immune response is initiated and the protein is eliminated[37]. Consistent with the safety of the spike mRNA vaccines, mRNA vaccines prevent post-COVID-19 thromboembolic complications[38] and a cohort study in 99 million COVID-vaccinated individuals showed no safety signals for haematological conditions[39]."
I don't believe this at all.
Their ref [37] is https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30292-8, from March 2020, and so does not tell us anything about mRNA "vaccines" in general, or those for COVID-19.
Their ref [38] https://heart.bmj.com/content/110/9/635.long only looks at those who contracted COVID-19, not those who suffered coagulation and perhaps died because of this following the gene therapy injections.
Their ref [39] https://www.sciencedirect.com/science/article/pii/S0264410X24001270 looked for adverse events only up to 42 days after the Pfizer, Moderna and AstraZeneca injections: "This multi-country analysis confirmed pre-established safety signals [increased rates of these pathologies in people who accepted the injections] for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis." So the article's statement that this "cohort study in 99 million COVID-vaccinated individuals showed no safety signals for haematological conditions" is obviously incorrect.
Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/. The immune system needs at least 50 ng/mL 125 nmol/L circulating 25-hydroxyvitamin D to function properly. This is twice or more what most people have, at least in winter, if they are not supplementing vitamin D3 properly and have not recently had a lot of UV-B exposure of ideally white skin.
Self-destructive, indiscriminate cell-destroying, inflammatory responses, even with healthy 25-hydroxyvitamin D, drive sepsis, severe COVID-19, Kawasaki disease, MIS-C etc. and surely disrupt neurogenesis, and so neurodevelopment. This is due to our ancestors evolving excessively strong inflammatory responses, which are directed at multicellular parasites, such as helminths (intestinal worms), due to ubiquitous helminth infections, with those helminths emitting one or more compounds which down-regulate these responses which target them. Now that we - and our companion and agricultural animals - are dewormed, we have generally excessive inflammatory responses, with a great deal of individual variation due to genetic differences and exposure to triggering compounds and pathogens.
Both helminthic therapy (introducing a relatively benign helminth infestation) and medically supervised extra-high 25-hydroxyvitamin D protocols (Coimbra) can be used to suppress a wide range of inflammatory autoimmune disorders, including multiple sclerosis, psoriasis, cluster headaches and migraine: https://vitamindstopscovid.info/06-adv/.