cGAS STING Interactions and Written Work
Part Four
All of these threads, and everything contained here, are a published work on Substack, and copyrighted, and protected under the Digital Millennium Copyright Act (DMCA). I do not give consent for the use of or republication of this material, under any format.
*****************************************
·
19/ A more general resource: The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer https://aacrjournals.org/cancerdiscovery/article/10/1/26/2314/The-Cytosolic-DNA-Sensing-cGAS-STING-Pathway-in…
1
2
·
20/
STING: a master regulator in the cancer-immunity cycle "The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway mediates anti-microbial innate immunity by inducing the production of type I interferons (IFNs) and inflammatory cytokines upon
1
2
·
21/ recognition of microbial DNA. Recent studies reveal that self-DNA from tumors and by-products of genomic instability also activates the cGAS–STING pathway and either promotes or inhibits tumor development
1
2
·
22/
this can kick in quickly, and does not require any kind of genetic mutation or modification by introduction of exogenous dsDNA into the body. If someone has a difference in this pathway genetically, this might contribute to differences in cancer susceptibility.
1
4
5
·
23/ An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer https://cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(18)30291-9…
1
1
7
·
24/ The Promoter Methylation Levels of MB21D1, TMEM173, TBK1, and IRF3 Are Variant in Different Types of Malignant Tumors
**********************************************************************************
the cardiomyocyte causing myocarditis (10:1 ratio positive lipids to nucleic acid molar ratio), and the positively charged lipids destroying bacteria, and forming adducts with RNA and DNA, frame shift caused by TWO mechanisms, mutations, STING path, cGAS, and other mutations
*********************************************************
·
5/ "Hot" tumors have T-cell infiltration and are more responsive to immunotherapy. "Cold" tumors lack T-cell infiltration and are less responsive to immunotherapy. The study focuses on converting "cold" TME into "hot" TME to enhance immunotherapy response.
1
·
6/ STING expression is crucial for appropriate type I interferon production and CD8 T-cell infiltration into tumors. The study reveals that, in GBM, the STING gene is epigenetically silenced by DNA methylation, specifically at the CpG site cg16983159 in the STING promoter region.
1
·
7/ (layman's terms at end, because holy eff) Treatment with DNMT inhibitor decitabine leads to demethylation at the cg16983159 site, increasing STING expression.Decitabine treatment activates the innate immune response and IFN-induced genes in previously unresponsive cell lines.
1
·
8/ GBM is resistant to standard treatments, and immunotherapy has shown limited success. The study suggests that DNMT inhibitors like decitabine may sensitize GBM to immunotherapies by reversing STING silencing.
1
·
9/ Concerns include the temporary effect of DNMT inhibitors and the need for therapies with lasting effects on demethylation. Efficacy in the tumor microenvironment, potential side effects of pan-DNMT inhibitors, and overcoming the blood-brain barrier are important considerations
1
·
10/ WTH did I just read simple terms analogy: Imagine your body is a city. Your immune system is a police force, always looking out for invaders. Your city, er, your body has a special alarm system, that is called the STING pathway. This STING pathway can detect specific
1
·
11/ threats, like dsDNA, and pathogens. However, in certain areas, the alarm does not work so well. one of these areas is where the glioblastoma hides out. In fact, the alarm system gets silenced, so the immune system, secondary alarm doesn't work so well.
1
1
·
12/ scientists have just discovered, that there is graffiti (wth!) this is actually molecular graffiti. Someone took a spray can of molecular graffiti, and shot it all over the alarm system's control panel, specifically at a spot called cg16983159. This graffiti, caused
1
1
·
13/ by a process called DNA methylation, makes the alarm system less sensitive and efficient in the GBM (glioblastoma ) neighborhood. This graffiti seems to be a common feature not only dangerous neighborhoods but also in normal areas during the city's development.
1
·
14/ A bunch of scientists thought they need to get rid of this molecular graffiti. They use a special cleaner called decitabine, which decimates that graffiti! When they clean up the graffiti in the GBM neighborhood, the alarm system kicks butt again, and the immune system,
1
1
·
15/ turns the previously "quiet" and immunosuppressive area into a place where the immune system is turned on again, and starts working again.
1
·
16/ now the immune system has a better chance of fighting off cancer after communication is turned back on between cancer cells and the immune system.
********************************************************************************
Brain Cancer:
STING cg16983159 methylation: a key factor for glioblastoma.
The same pathway activated by dsDNA🧬, the STING pathway, if "silenced" could reverse the progression of cancer and enhance the effectiveness of immunotherapy.
Unroll available on Thread Reader
https://twitter.com/_HeartofGrace_/status/1732169560839586043
2/ The article: STING cg16983159 methylation: a key factor for glioblastoma immunosuppression
nature.com/articles/s4139…
STING cg16983159 methylation: a key factor for glioblastoma immunosuppression - Signal Transduction and Targeted Therapyhttps://www.nature.com/articles/s41392-022-01093-w
3/ Background on cGAS–STING Pathway:
Cancer cells contain high levels of cytosolic DNA.
The cGAS–STING signaling axis is a major sensor of cytosolic DNA and triggers the innate immune response, leading to the production of pro-inflammatory cytokines, including type I interferons.
4/ (Agents of cancer immunosurveillance: HSPs and dsDNA)
cell.com/trends/immunol…
https://www.cell.com/trends/immunology/fulltext/S1471-4906%2822%2900053-9
5/ "Hot" tumors have T-cell infiltration and are more responsive to immunotherapy.
"Cold" tumors lack T-cell infiltration and are less responsive to immunotherapy.
The study focuses on converting "cold" TME into "hot" TME to enhance immunotherapy response.
6/ STING expression is crucial for appropriate type I interferon production and CD8 T-cell infiltration into tumors.
The study reveals that, in GBM, the STING gene is epigenetically silenced by DNA methylation, specifically at the CpG site cg16983159 in the STING promoter region.
7/ (layman's terms at end, because holy eff)
Treatment with DNMT inhibitor decitabine leads to demethylation at the cg16983159 site, increasing STING expression.Decitabine treatment activates the innate immune response and IFN-induced genes in previously unresponsive cell lines.
8/ GBM is resistant to standard treatments, and immunotherapy has shown limited success.
The study suggests that DNMT inhibitors like decitabine may sensitize GBM to immunotherapies by reversing STING silencing.
9/ Concerns include the temporary effect of DNMT inhibitors and the need for therapies with lasting effects on demethylation.
Efficacy in the tumor microenvironment, potential side effects of pan-DNMT inhibitors, and overcoming the blood-brain barrier are important considerations
10/ WTH did I just read simple terms analogy:
Imagine your body is a city. Your immune system is a police force, always looking out for invaders.
Your city, er, your body has a special alarm system, that is called the STING pathway.
This STING pathway can detect specific
11/ threats, like dsDNA, and pathogens. However, in certain areas, the alarm does not work so well. one of these areas is where the glioblastoma hides out. In fact, the alarm system gets silenced, so the immune system, secondary alarm doesn't work so well.
12/ scientists have just discovered, that there is graffiti (wth!)
this is actually molecular graffiti.
Someone took a spray can of molecular graffiti, and shot it all over the alarm system's control panel, specifically at a spot called cg16983159. This graffiti, caused
13/ by a process called DNA methylation, makes the alarm system less sensitive and efficient in the GBM (glioblastoma ) neighborhood. This graffiti seems to be a common feature not only dangerous neighborhoods but also in normal areas during the city's development.
14/ A bunch of scientists thought they need to get rid of this molecular graffiti. They use a special cleaner called decitabine, which decimates that graffiti!
When they clean up the graffiti in the GBM neighborhood, the alarm system kicks butt again, and the immune system,
15/ turns the previously "quiet" and immunosuppressive area into a place where the immune system is turned on again, and starts working again.
16/ now the immune system has a better chance of fighting off cancer after communication is turned back on between cancer cells and the immune system.
********************************************************************************
Second verse, same as the first.
Thyroid damage and auto immune is linked to dsDNA.
dsDNA is found in the current plasmid DNA contamination.
This is slightly different in the thyroid ( histone H2B)
Study + cases on 💉injury.
Unroll available on Thread Reader
2/ The Study: Fragments of Genomic DNA Released by Injured Cells Activate Innate Immunity and Suppress Endocrine Function in the Thyroid
Endocrinology, Volume 152, Issue 4, 1 April 2011, Pages 1702–1712,
https://doi.org/10.1210/en.2010-1132
3/ (this part is not in study, but I checked--same pathway to start as what happens in AAD in previous thread in the heart with aortic dissection and dsDNA)
Starting event: dsDNA from DNA plasmid contamination enters cells via a lipid nanoparticle from a modRNA "vaccine".
4/ fragments of plasmid DNA are recognized by cellular receptors cGAS (cyclic GMP-AMP synthase) and activate the STING pathway. This is the internal "sensors" of a cell that something is wrong. dsDNA does not belong in the cytoplasm of a cell. This triggers a cascade.
5/ leading to immune responses in the thyroid. The release of inflammatory cytokines and chemokines, and induction of MHC expression, leads to STING activation and the first immune system attack on the thyroid. Just like the heart study, we are looking at TWO immune responses.
6/ So, first the cell i the thyroid recognizes the fragments of dsDNA as bad, then it activates the STING pathway, which causes inflammation and damage to the tissue in the thyroid. This causes some damage, which is going to make the thyroid release its OWN dsDNA, just like
7/ in the heart study where the cells in the aorta did the same thing, leading to damage.
But in this case, it will lead to sustained autoimmune attack.
In this study. thyroid cells were "injured", thus causing the release of it's OWN genomic DNA into the cytosol.
8/ This release is associated with the production of type I interferons, inflammatory cytokines, and chemokines.
In the heart study (see linked previous thread), the presence of cytokines, and chemokines caused the aorta to rupture in the heart, rapidly. But that is not what
9/ happens to the thyroid. Something else occurs.
dsDNA strongly suppresses the expression of sodium/iodide symporter and radioiodine uptake in thyroid cells.
Histone H2B also binds to the dsDNA.
dsDNA derived from host cells can activate both immune and non-immune cells
10/ when introduced into the cytosol, activating a set of genes, including those encoding MHC, costimulatory molecules, TAP1, immunoproteasome subunits, STAT1, IRFs, and PKR.
11/Histone H2B recognizes extrachromosomal genomic DNA fragments in the cytosol, activating signal transduction pathways.
The release of histone H2B from the nucleosome and its recognition of extrachromosomal genomic DNA fragments activates inflammatory genes in thyroid cells.
12/ But here's the wild fact: thyroid cells are capable of activating innate and acquired immune responses without interacting with immune competent cells.
That's right.
ALSO lipopolysaccharide, dsDNA, and dsRNA, activate the same immune responses. If there was LPS from
13/ the E coli that the DNA plasmids were "grown in" that was not filtered out properly, this would also do this.
Then what occurs is aberrant MHC class II expression in thyroid cells create thyroid autoantigens (TPO antibodies), triggering autoimmune responses.
14/ so:
dsDNA plasmid contamination--> thyroid cells--->DNA recognition by cGAS-->STING pathway activation-->>immune system attacks thyroid--> thyroid releases its own dsDNA as a result of damage-->sustained auto immune reaction (hashimotos/graves) due to altered MHC expression
15/ Tl;DR (too long didn't read): the recognition of
plasmid DNA fragments by cGAS and subsequent activation of the STING pathway in the thyroid can indeed trigger immune responses, leads to inflammation and contributing to autoimmune reactions in the thyroid.
16/ additional info: Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves’ Disease: An Encrypted Message Sent by Animal Models
doi: 10.3389/fendo.2016.00144
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107990/
17/🚨 Graves’ Disease after mRNA COVID-19 Vaccination, with the Presence of Autoimmune Antibodies Even One Year Later
2023 May 3. doi: 10.3390/vaccines11050934
ncbi.nlm.nih.gov/pmc/articles/P…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222727/
18/ Graves' Disease Following COVID-19 Vaccination
DOI: 10.7759/cureus.24418
19/ SARS-CoV-2 vaccine may trigger thyroid autoimmunity: real-life experience and review of the literature
2022 Jul 12. doi: 10.1007/s40618-022-01863-x
ncbi.nlm.nih.gov/pmc/articles/P…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277984/
20/ COVID-19 vaccination and thyroiditis
doi: 10.1016/j.beem.2023.101759 [Epub ahead of print]
ncbi.nlm.nih.gov/pmc/articles/P…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981269/
21/
22/ 🚨🚨Enlargement of a metastatic lymph node from differentiated thyroid cancer after COVID-19 vaccination
doi: 10.1007/s12020-023-03367-x [
@P_J_Buckhaults ncbi.nlm.nih.gov/pmc/articles/P…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113119/
23/ 🚨!!!!! Hashimoto encephalopathy as a probable complication of vaccination against SARS-CoV-2,
(THAT IS AUTO IMMUNE ATTACK ON THE BRAIN!)
.
doi: 10.1016/j.nrleng.2022.09.005 [Epub ahead of print]
24/ 🚨🚨🚨🚨🚨🚨🚨🚨🚨🚨💉🧬🧬🧬!!!!!!!!!!!!!!!!!!!!!!!!!!!
COVID-19 mRNA vaccine-associated encephalopathy, myocarditis, and thrombocytopenia
@DrJBhattacharya @drdrew ncbi.nlm.nih.gov/pmc/articles/P…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080027/
*********************************************************************
11/ And if mutations occur in the cGAS STING pathway, or if it is continually activated, this can cause devastating human diseases. https://jbc.org/article/S0021-9258(23)01894-X/fulltext…
·
68
Views
1
1
Most relevant
Post your reply
Reply
·
12/ "Interestingly, genetic gain-of-function mutations in STING have been identified in humans with an autoinflammatory disease called STING-associated vasculopathy with onset in infancy (SAVI) (22). Patients with SAVI develop fever, skin lesions, digital ulcerations, and
1
1
2
·
13/ interstitial lung disease (pulmonary fibrosis) (22, 57, 58). Known SAVI-causing mutations include those found in the connector helix loop. STING activation can also induce autophagy. mutations in COPA cause COPA syndrome, a rare autoimmune disease by enhanced STING signaling
1
·
14/ mutations in STING cause inflammation and immunodeficiency. The cGAS-STING pathway can mutate through various mechanisms, and lead to human diseases. Somatic mutations are changes in DNA in non-germline cells. These mutations are not inherited but arise during an
1
·
15/ individual's lifetime. Exposure radiation, or mutations that occur via, I don;t know, something, MAY induce somatic mutations in the genes involved in the cGAS-STING pathway.
1
·
16/ Germline mutations occur in DNA of germ cells (sperm and egg cells) and can be passed on to offspring. Inherited mutations in genes related to the cGAS-STING pathway may predispose people to alterations in immune responses.
1
·
17/ cGAS STING can also be mutated via errors during DNA replication, leading to mutations. These errors may arise spontaneously or be influenced by various factors, including cellular stress or exposure to mutagenic agents--like plasmid DNA contamination.
1
·
18/ Changes in the epigenetic landscape in or around cGAS or STING genes may be a pathway to dysregulation. Mutations that drive oncogenic transformation in cells may affect the cGAS-STING pathway.
1
1
·
19/ Dystregulation by dsDNA can impact the cGAS STING pathway, and might possibly, mutate the cGAS, leading to multiple health concerns.
******************************************************************************
·
11/ And if mutations occur in the cGAS STING pathway, or if it is continually activated, this can cause devastating human diseases. https://jbc.org/article/S0021-9258(23)01894-X/fulltext…
1
1
·
12/ "Interestingly, genetic gain-of-function mutations in STING have been identified in humans with an autoinflammatory disease called STING-associated vasculopathy with onset in infancy (SAVI) (22). Patients with SAVI develop fever, skin lesions, digital ulcerations, and
1
1
2
·
13/ interstitial lung disease (pulmonary fibrosis) (22, 57, 58). Known SAVI-causing mutations include those found in the connector helix loop. STING activation can also induce autophagy. mutations in COPA cause COPA syndrome, a rare autoimmune disease by enhanced STING signaling
1
·
14/ mutations in STING cause inflammation and immunodeficiency. The cGAS-STING pathway can mutate through various mechanisms, and lead to human diseases. Somatic mutations are changes in DNA in non-germline cells. These mutations are not inherited but arise during an
1
·
15/ individual's lifetime. Exposure radiation, or mutations that occur via, I don;t know, something, MAY induce somatic mutations in the genes involved in the cGAS-STING pathway.
1
·
16/ Germline mutations occur in DNA of germ cells (sperm and egg cells) and can be passed on to offspring. Inherited mutations in genes related to the cGAS-STING pathway may predispose people to alterations in immune responses.
1
·
17/ cGAS STING can also be mutated via errors during DNA replication, leading to mutations. These errors may arise spontaneously or be influenced by various factors, including cellular stress or exposure to mutagenic agents--like plasmid DNA contamination.
1
·
18/ Changes in the epigenetic landscape in or around cGAS or STING genes may be a pathway to dysregulation. Mutations that drive oncogenic transformation in cells may affect the cGAS-STING pathway.
1
1
·
19/ Dystregulation by dsDNA can impact the cGAS STING pathway,
***************************************************************
his study comes in handy. The cGAS-STING pathway "sees" aberrant nucleic acids. The DNA plasmids are already aberrant in more than one way--it's bacterial, recombinant, has CpG motifs, AND, according to the study breakdown in the thread below, is being mutated inside the LNP!
Quote
Christie Laura Grace
@_HeartofGrace_
·
Sep 20, 2023
1/ Impurities in Positively Charged Lipids in the LNP, can MUTATE mRNA in LNP (Packer et al., 2021); potentially mutating other nucleic acids (RNA,DNA) that could lead to: -Point mutation -Aberrant Protein (toxic) -Noncoding (can be oncogenic) -Misfold that protein/aggregation
Show more
·
2,578
Views
3
26
45
4
Most relevant
Post your reply
Reply
·
2/
Quote
Christie Laura Grace
@_HeartofGrace_
·
Nov 16, 2023
The cGAS-STING pathway in humans, can detect and be activated by pieces of DNA, bacterial DNA, AND RNA (all are in the LNP!) If activated (which is outside of the nucleus), this can lead to multiple diseases, including autoimmune disease and cancer. https://ncbi.nlm.nih.gov/pmc/articles/PMC8851069/…
1
2
·
3/
Quote
Phillip Buckhaults
@P_J_Buckhaults
·
Nov 16, 2023
Replying to @_HeartofGrace_ @DrJBhattacharya and @drdrew
https://nature.com/articles/s41586-018-0629-6
best not be publishing my work
***********************************************************************
he cGAS-STING pathway in humans, can detect and be activated by pieces of DNA, bacterial DNA, AND RNA (all are in the LNP!) If activated (which is outside of the nucleus), this can lead to multiple diseases, including autoimmune disease and cancer. https://ncbi.nlm.nih.gov/pmc/articles/PMC8851069/…
·
12.8K
Views
6
89
168
46
Most relevant
Post your reply
Reply
·
https://epub.ub.uni-muenchen.de/75126/1/hopfner_hornung_2020.pdf…
1
12
·
2/ TN;DR (too nerdy;didn't read) Base pair requirements (size/length) to activate the cGAS-STING pathway: "The dimer structure suggests that ~16–18 bp of dsDNA should, in principle, be sufficient to fully activate cGAS. However, generic DNA <20 bp bound poorly to the cGAS
Show more
2
4
17
1.2K
****************************************************************************
DNA contamination found in c@vid vaccines IS dsDNA. Humans have a pathway called, cGAS–STING pathway. This pathway can be activated by dsDNA (PLASMID DNA), causing autoinflammatory, autoimmune, degenerative disease, and cancer. NO NUCLEUS NEEDED. https://nature.com/articles/s41577-021-00524-z
******************************************************************
DNA PLASMID CONTAMINATION in mod RNA "vaccines" does NOT have to enter the nucleus to cause cancer. Recent advances have now expanded the roles of cGAS-STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to drive tumorigenic behaviors. "The cytosolic DNA-sensing cGAS-STING pathway in cancer": can be activated by dsDNA outside of the nucleus, which can be in the form of DNA plasmid contamination, which was recently found by multiple scientists in the c@vid "vaccines", thus, causing aggressive, unstable cancer. https://ncbi.nlm.nih.gov/pmc/articles/PMC7151642/
*****************************************************
DsDNA (DNA plasmid contamination in c@vid "vaccines) would do this too. SAME PATHWAY (cGAS) Acute myocardial infarction is accompanied by massive cardiomyocyte necrosis and tissue inflammation. In multiple studies, it was reported this extensive cardiomyocyte necrosis is also associated with elevated circulating mtDNA https://ncbi.nlm.nih.gov/pmc/articles/PMC5840331/#:~:text=Acute%20myocardial%20infarction%20is%20accompanied,levels%20%5B91%E2%80%9393%5D….
*******************************************************************
DNA PLASMID CONTAMINATION in modRNA vaccines can cause STROKES Same pathway as CANCER. IT does NOT need to enter the nucleus. cGAS-STING pathway is mediator in response to dsDNA. DNA plasmid contamination is dsDNA.
*****************************************************
Frank can sue on this one too. We both can. Take our sh1T, and you will be served.
https://rumble.com/v58fgjp-the-pathway-to-save-the-world-ft-christie-laura-grace-72524.html
cGAS STING Pathway activation by DNA Plasmid Contamination, SPIKE, and LPS in modRNA "vaccines": AIDP, Myocarditis, Stroke, Aortic Dissection, and More: Overview, and Biopsy Methods for Detection. https://christiegrace.substack.com/p/cgas-sting-pathway-activation-by…
ANCER: "COMBINED" FEEDBACK LOOP of cGAS STING AND APOBEC: DNA plasmid in LNP +DS RNA triggers cGAS STING AND induction of DNA deaminase APOBEC3A + nuclear DNA damage: https://christiegrace.substack.com/p/cancer-combined-feedback-loop-of…
**********************************
https://threadreaderapp.com/thread/1825258055489188295.html