TSOI lung strategies

This forum is to discuss general things concerning TSOI.
Codycrusher
Posts: 85
Joined: Sat Feb 13, 2021 2:29 pm

Re: TSOI lung strategies

Post by Codycrusher »

Nonetheless if a pharma comes to you offering 15-25 billy licensing deal or something really good, it would be worth completely taking it into consideration because that puts the share price and the future of the company in a really bright spot if accepted once offered, I’m sure there’s room for negotiation possibly.
Also if you get a big licensing pharma deal in the big Billy’s, than you could fund all of TSOI’s ventures and make something crazy out of this company, you could spend extra money to expedite the research on stemcells and everything and get them through the FDA process a lot faster. Plus you could start up like 4-5 phase 1s all at once if you have the science to backup different category’s. There really is so much you could do with the proper funding.
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TimGDixon
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Joined: Fri Jun 26, 2020 4:36 am

Re: TSOI lung strategies

Post by TimGDixon »

We would consider any reasonable offer but we are also not desperate - our only early interest would be to 1) license the US Govt to make and have made, cells to treat all americans with lung injury due to covid-19 or 2) license pharma to do same. All the other lung pathologies we're not giving up anytime soon but we do think the americans are priority with lung injury from covid.
4realz
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Joined: Wed Jan 20, 2021 6:49 am

Re: TSOI lung strategies

Post by 4realz »

“my sense is we become too big of a threat to those other pharma giants when i can produce all the cells neccessary to treat all those patients while sitting on your river in Idaho”

So. Tim, what are the plans moving forward with a facility in Idaho? Obviously the move there was strategic and I remember reading some about the legal reasons why you chose Idaho but would love a brief update; talking plans of a full cGMP Manufacturing facility focused on producing ‘off the shelf’ Jadicell and nutraceuticals ‘in house’ on a larger scale for world use? :D :!: :!: :!: Purely conceptual or plans on paper and in the works? Estimated time frame to groundbreaking..? 😉

Know, if this is even a potential direction, it all would hinge on what unfolds in the near future with JadiCell lung and StemVacs V, funding; however, just a little more insight into the long term (loose) agenda might help us justify a LONG haul mentality as a whole. I have this vision of a TSOI facility comparable to that of IBIO’s cGMP Manufacturing facility; but brought into reality VERY quickly, and possibly with govt backing, to meet a stateside and possibly even world demand. How far left field is my train of thought?

Just where my mind goes ... Also .. will fishing be allowed from the walking bridge? 😆

Won’t be offended if you don’t or can’t answer; for the record are just my late night musing. I don’t believe these ideas were actually implied at all that I can recall. production facilities; it’s just how my mind works. Production to meet demand is what it’s all about. Create the need/ market and make it happen!! 👍
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TimGDixon
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Re: TSOI lung strategies

Post by TimGDixon »

Nothing wrong with having a surge of thoughts and ideas in the middle of the night - its what i do most nights hahahahah

Our move to Idaho was a corporate move to escape fines being levied against public co's for not complying with new laws that are completely unconstitutional - it is in essence a minority take-over of boards by the State and homey don't play that shit... so first and foremost was to buy a piece of land outright and change our physical corporate address - DONE!

Next up is to build some infrastructure to support our future and even though the river property is 15 acres, its obviously not enough and we are pursuing much larger land tracks without saying too much... The future of that is less about manufacturing and more about end care - think stem cell clinic, think cancer clinic.

We don't currently have a bridge and if you want to get across the American ou have to wade like i just did and man that water is cold - pure snow melt right now - however we are going to build a bridge and you can fish off it all you like... 4realz
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curncman
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Joined: Fri Jun 26, 2020 8:27 am

Re: TSOI lung strategies

Post by curncman »

Tim. You are right California is going in a downward spiral and heading towards socialism and killing inventions in field of software, Drugs and automotive industry. Hence companies like apple google Tesla and TSOI have moved out of California to keep the tradition of invention and trade.

I am glad TSOI has already aligned its products with changing trends in future of medicine. Cancer immunotherapy and stem cell clinic are most high growth sectors in pharma industry and i am glad this can be accomplished with no heavy chemical based manufacturing facility and zero pollution to the environment.

Post pandemic no reason to have huge glass door offices in downtowns when everything can be done from any remote location with the advent of e-commerce companies like Amazon. TSOI can have millions of JADICELLS vials ready in cryogenic freezers at the stemcell lab facilities all over USA and all hospital providers can place online orders for JADICELLS they shall have in less than 48 hours to revive the severely lung damaged patients due to sars-cov2,ARDS, vaping, asthma, pneumonia and possibly lung cancer .

Or better yet come down to TSOI STEMCELL clinic in Elk City IDAHO offering quality care under the guidance of world class doctors offering worlds most personalized &advanced cancer immunotherapy to save lives of many cancer patients who otherwise are dying anyways despite taking chemotherapy drugs offered by the BIGPHARMA. It’s time for a change for all patients suffering from cancer, arthritis, CTE/tbi , cardiac problems to adopt TSOIs novel personalized Stemcell therapy for a better life and prosperity!
trader32176
Posts: 2696
Joined: Fri Jun 26, 2020 5:22 am

Re: TSOI lung strategies

Post by trader32176 »

Metformin is in the news again / TSOI & Metformin

Metformin a drug that diabetics use is in the news again :

Metformin potently inhibits SARS-CoV-2-induced cytokine release in monocytes

6/6/21


https://www.news-medical.net/news/20210 ... cytes.aspx


During the ongoing coronavirus disease 2019 (COVID-19) pandemic, it has become clear that hyperactive inflammation is sometimes induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via its spike antigen. This is mediated by cytokines released by inflammatory cells, such as monocytes.

An interesting new bioRxiv* preprint reports the suppression of monocyte glycolysis and cytokine production when exposed to the virus, following pretreatment with the commonly used drug, metformin.

Background


The hyper-inflammatory reaction induced by SARS-CoV-2 is believed to be largely responsible for much of the organ damage and respiratory distress associated with COVID-19. Various anti-inflammatory drugs have been used to treat this disease with inconsistent success.

The drugs’ lack of success is likely due to the limited understanding of the mechanisms that are responsible for the intense inflammation seen in COVID-19.

To this end, no common pattern of cytokine release has been identified among patients with severe or critical COVID-19. This has led to a diverse nomenclature for this syndrome, including cytokine storm, multisystem inflammatory syndrome, or macrophage activation syndrome.

Monocytes are innate immune cells that are classified as a subtype of mononuclear phagocytes. In COVID-19, monocytes reflect changes such as low human leukocyte antigen DR (HLA-DR) expression, high levels of CD16 expression, and cytokine production, all of which indicate a hyperinflammatory state.

Monocytes give rise to macrophages, which engulf pathogens and cellular debris, including SARS-CoV-2. However, this virus does not actually infect monocytes.

Immune cells in inflammation

In conditions that favor inflammation, as is the case in the SARS-CoV-2 infection, immune cells become metabolically active to promote inflammation and respond to the pathogenic stimulus.

To sustain such high rates of metabolism, immune cells will typically switch to aerobic glucose pathways that yield abundant adenosine triphosphate (ATP) molecules. As a result, these cells increase their production of pro-inflammatory mediators.

SARS-CoV-2 also reprograms lipid metabolism in the monocyte, which leads to the formation of lipid droplets that precede the production of inflammatory cytokines.


HIF-1a-mediated switch to glycolysis



The current study describes the phenomenon that occurs when monocytes bind with the SARS-CoV-2 spike S1 protein. This binding resets the metabolism of monocytes back to anaerobic glycolysis in a dose-dependent manner.

This increase in glycolysis is associated with an increased release of pro-inflammatory cytokines, notably interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a). These cytokines are closely linked to the COVID-19-related cytokine storm.

This switch to anaerobic metabolism is due to the presence of hypoxia-inducible factor-1a (HIF-1a). If this reprogramming could be inhibited, the onset of inflammation could likely be prevented.

Indeed, the HIF-1a inhibitor chetomin, when used to pretreat the macrophage before exposure to S1, led to the suppression of glycolysis and cytokine release.

“HIF-1a appears to be a master regulator of both glycolytic reprogramming and inflammatory activation of monocytes under S1 stimulation.”

Glycolysis suppression linked to cytokine reduction


Pre-treatment of monocytes with the glycolysis inhibitor 2-deoxyglucose (2-DG) also led to a drastic fall in cytokine levels. However, this molecule is also capable of broadly inhibiting mitochondrial metabolism.

Therefore, a control experiment was performed in which monocytes were deprived of glucose. When exposed to S1, the glucose-deprived monocytes experienced an increase in oxidative phosphorylation using fatty acid oxidation, which led to a rise in cytokines despite the inhibition of glycolysis. This was not seen with the use of 2-DG, which suppressed both glycolysis and mitochondrial metabolic pathways.

Though both chetomin and 2-DG inhibited glycolysis and cytokine release from monocytes following exposure to the spike antigen, they are not suitable for clinical administration. Conversely, metformin, which decreases glucose production, is already approved and widely used for the treatment of diabetes as well as for geriatric patients.

Pre-treatment of the monocytes with metformin before exposure to the spike antigen led to the suppression of glycolysis and mitochondrial respiration within the cells. Simultaneously, metformin pre-treatment was also found to prevent cytokine production in response to S1 exposure.

Further, pre-treatment with metformin led to the inhibition of cytokine release from monocytes following their exposure to wild-type SARS-CoV-2. This indicates that metformin is also able to block the effect of other pro-inflammatory proteins besides the spike protein.

What are the implications?

The current study identifies a possible mechanism responsible for hyperactive cytokine release during the early phase of the innate immune response to the virus. Since active infection with the virus does not occur within monocytes, this inflammation appears to be activated by either the viral spike protein, other structural viral proteins, or viral genomic material.

The exposure of the monocytes to viral proteins may be due to viral antigenemia and/or a result of the direct binding of the virus to macrophages. This S1-monocyte/macrophage recognition may also underlie the local inflammation of muscle tissue that is widely reported following COVID-19 vaccination.

Monocytes have low angiotensin-converting enzyme 2 (ACE2) levels, which is the best-known receptor for the SARS-CoV-2. However, the spike protein also binds to C-type lectins, which are signaling molecules on myeloid cells, as well as to the CD147 receptor that is present at high levels on monocytes and macrophages.

The finding that metformin regulates immunometabolic pathways triggered by SARS-CoV-2 is significant, as it offers a potential therapeutic approach to suppress inflammation in COVID-19. As an inexpensive, safe, and widely available drug, metformin offers an excellent avenue for further investigation.

“In summary, the SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin, and metformin likewise suppresses inflammatory responses to live SARS-CoV-2. This has potential implications for the treatment of hyperinflammation during COVID-19.”

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:


Cory, T. J., Emmons, R. S., Yarbro, J. R., et al. (2021). Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 and Spike Protein Subunit 1. bioRxiv preprint. doi:10.1101/2021.05.27.445991. https://www.biorxiv.org/content/10.1101 ... 7.445991v1


$TSOI Metformin PRs

Therapeutic Solutions up big on patent filing for QuadraMune in COVID-19

https://seekingalpha.com/news/3593647-t ... idminus-19

7/22/20

Nano cap Therapeutic Solutions International (OTCPK:TSOI +50.0%) jumps on 32% higher volume in reaction to its announcement that is has filed a patent application with the USPTO covering the use of QuadraMune and type 2 diabetes med metformin to treat COVID-19-associated lung damage.
It says QuadraMune, a nutritional supplement, protects the lung from inflammation and the effect is "markedly amplified" by concurrent administration of metformin.


QuadraMune(TM) Synergizes with Metformin to Stimulate Anti-Viral Defenses in Pilot Clinical Trial

Nutraceutical Currently under Investigation for COVID-19 Prevention Stimulates Natural Killer Cell activity in Diabetics Taking Metformin


https://www.wfmz.com/news/pr_newswire/p ... 5ad59.html
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