Ssri,Epigenetic Changes and Azicitidine(demethylating agent)

[zadig777]

Greeting fellow sufferers hope this is an active forum here )
as i hope many of u have seen already,that even after 10 yrs no treatment was found to be sufficent for pfs and pssd
many theories were tried with no to little success 0-10%

the latest study regarding ssri is that these drugs cause epigenetic changes hypo and hypermethylation,where turning ON and OFF of genes happen

The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

New study reveals the epigenetic effects of Citalopram
by nasibi » Sun Oct 21, 2018 8:56 am
The first study of its kind. Finally a step in the right direction.

The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

Riya R. Kanherkar, Bruk Getachew, [...], and Antonei B. Csoka

Abstract

"Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 μM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p < 0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFκB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugs can have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health."

"postmarketing clinical trials documented adverse effects mostly in terms of sexual dysfunction including anorgasmia, erectile dysfunction, genital anesthesia, and diminished libido in almost 75% of treated patients [6, 10–12]. Interestingly, these side effects appear to endure after treatment in some cases [13, 14], which is hard to explain using a standard pharmacological model.

"A plausible cause of these persistent side effects is changes to the epigenome [1–3]. The epigenome of a cell is a unique, dynamic entity consisting of distinct DNA methylation patterns across gene enhancers, promoters, and bodies along with histone modifications that do not involve any changes to the actual DNA sequence...
Epigenetic changes resulting from environmental effects such as traumatic life events can rewire neural circuits and alter neurotransmitter and endocrine systems resulting in stress-related psychiatric disorders such as major depression or posttraumatic stress disorder [15]. Based on this evidence, it can be posited that potential unknown mechanisms of action of SSRIs, as well as side effects, could be through epigenetic modification of genes [1, 2, 15]."

"Finally, top physiological systems affected by citalopram identified by IPA included nervous system development diseases and function with 24 genes involved in neurotransmission (p value = 1.25E − 02), 23 genes related to outgrowth of neurites (p value = 1.59E − 02), 9 genes related to excitatory postsynaptic potential (p value = 1.48E − 02), 6 genes related to quantity of synapse (p value = 1.21E − 02), and 3 genes related to loss of dendritic spines (p value = 1.42E − 02). Additionally, 47 genes related to morphology of the nervous system (p value = 1.95E − 02), 35 genes related to development of the central nervous system (p value = 1.45E − 02), 21 genes related to sensation (p value = 3.67E − 03), 11 genes related to development of the cerebral cortex (p value = 1.20E − 02), 8 genes related to abnormal morphology of the hippocampus (p value = 1.72E − 02), 7 genes related to abnormal morphology of the synapse (p value = 2.96E − 03), and 3 genes related to development of the hypothalamus (p value = 1.50E − 03) were identified (Supplement 8). These results, in particular, were interesting because of the known mechanism of citalopram action on the nervous system-based serotonin transporter, along with unknown targets affected by epigenetic mechanisms, that can be further delineated in the future."

Among the genes downregulated (turned off) are also those related to the neuroendocrine system. Like Gnrh, LH, FSH, the dopa pathway, Oxytocin etc.

"We have previously outlined a potential mechanism for understanding the direct and indirect effects of environmental factors, including pharmaceutical drugs [1, 15] on the epigenome. Here, we attempted to confirm the hypothesis that pharmacological agents can cause permanent changes via epigenetic reprogramming. The results show that our first test drug, citalopram, can cause genome-wide DNA methylation alterations as revealed by significant differential methylation in hundreds of genes, as well as predicted impact on signaling pathways and/or physiological systems"

"One potential limitation with this pilot study is that HEK-293 cells have not been shown to express high levels of the serotonin transporter, SERT, nor been shown to synthesize high amounts of serotonin in the extracellular medium, compared to neurons. Hence, in this case, we argue that the effects of citalopram seen on DNA methylation in these cells are more likely to be 5HT-independent. HEK-293 cells are known to abundantly express a diverse repertoire of receptors such as β2-adrenergic, muscarinic acetylcholine, sphingosine-1-phosphate, P2Y1 and P2Y2, corticotropin-releasing factor type 1, and somatostatin- and thyrotropin-releasing hormone receptors, and citalopram has been shown to interact strongly with some of these receptors, in the concentration range used in this study, so it may well be eliciting epigenetic effects through these pathways. Moreover, the data is consistent with our initial hypothesis that the epigenetic effects of chemicals could be both direct (acting directly on DNA or DNA-modifying enzymes) and indirect (acting through receptors or signaling pathways) [1, 15], in which case a direct effect on SERT is not necessary to induce epigenetic changes. It is also possible that in the presence of 5-HT and SERT, we may see different epigenetic effects of citalopram from those observed in the HEK-293 cells. In any case, we intend to repeat this experiment using primary human neurons as the target cells, rather than a proliferating cell line, in order to gain greater insights into potential in vivo effects."



Thats why we choose,Nasibi came to this idea originaly!,that we use azacitidine for reversing the silencing of the genes,to turn ON the genes that were turned OFF by ssri

Only one sufferer in the history of pfs and pssd together followed this routte

Reversing silenced AR signal with demethylating agents - A promising treatment option?

I contacted few people but they never heard of the guy who tried Aza for 5 days and got improvements
They speculate that its either hes dead or healed!

What are ur thoughts about this?

I will call nasibi to join the conversation since he know much more about the science of this matter


ALSO!!

If anyone know a site where i can order without prescribtion a legitime azacitidine plz pm me or refer me to that site

Regards

 

[Reverse]

Yep, that's the overall key factor. Epigenetics...

inhibit one and watch the others switch on or off...all depends

CRISPR now working on proteins and epigenetics instead of directly cutting and pasting genes...I think

can epigenetics be improved thru generations naturally idk maybe. but science wackos only want to edit using their tech which is probably more quackery like most of pharma.

some sources say it takes 5 generations for bad things to change but that's "old and mythical" texts, like tcm philosophy or bible ... idk...no lab tests. Can we speed up the epigene (cleansing) reset it naturally? idk...would only take a few years but there's no investors smh.

example: if parent had diabetes, then child is 3 x more likely to develop it...so more care is needed.

I do know that test booster ingestion by female when pregnant leads to male born with enlarged pistol....don't remember where the study is. return to normal after birth though.

could that be a epigenetics short term or long term affect or will child have Hyper testosterone level as adult? agai there is no follow up research.

Fak medicine, the scientists killed Jesus , aryuveda and tcm because they exposed their snake oil and sorcery.

 

[zadig777]

that was not the point obviously but whatever..

 

[bruschi11]

This thread is what makes people go insane.

All that happened to us is we got an imbalance which made us sick. Whether genes were turned on or off- who knows. But fixing genes is attainable without all the science so many are looking into.

You just need health to fix this stuff. What makes you healthy, will fix your genes

And sometimes a good diet and exercise isn’t enough. People got really sick from these drugs including myself. Sickest of the sick because of these evil companies.

But finding health where one balances system, pathogens removed, deficiencies filled up, heavy metals/ toxicities removed etc etc, there is nowhere for a person to go but up.

“Oh I did 10 liver flushes and didn’t get better.” Maybe liver flush isn’t key to getting your respective health back.

“Oh I fasted for 21 days and got worse after.” What did you eat and do for your body after the fast?

If I’ve done it to degree I got better with pure health itself, I’m sure anyone can do it.

 

[Helen]

@zadig777


I used sulphoraphane in my recovery.

Clomipramine <i>In Vitro</i> Reduces Glucocorticoid Receptor Function in Healthy Subjects but not in Patients with Major Depression SSRI upregulates GR receptor. SO demethylating agents like sulphoraphane destroy AR and GR.


Sulphoraphane is electrolytes protocol for this reason


Also I used valproic acid for POIS people 5 years ago. And high dose Vitamin C which is also demethylates.


the new demethylating agent decitibine can be used also.


People have different cases. for some these things made them very bad.


you need to understand that most of these hypomethylated or hypermethylated genes are the outcome of the present mineral balance in the body.

 

[Helen]

@zadig777 Also on our POIS forum, many people benefited from methylation protocol like Freddd

And were fully recovered with it.

So hypo and hypermethylation is def present in PSSD and PFS> low and high histamine cases


low and high copper.

This is why in case of overmethylation Hoffer, and Pfifer used 3 grams of niacin a day to lower brain copper.

 

[zadig777]

@Helen

we are going to use azacitidine
decitibine works on proliferating cells,and only on few cells like bone marrow etc..

azacitidine works on RNA level not DNA,so it affects all cells,demethylates all not only proliferating cells or bone marrow

i will try to get nasibi here so u can further discuss

regards

 

[Helen]

@zadig777 Also you need to undertstand that demethylation of genes are heavily dependant on glutathione. Since it is vitamin C which controls demthylation. process.

And in slow oxidizers in PFS and pssd people. vitamin C is zero, since most of them got a viral infection.


So the redox status, does not allow a person to methylate properly and demethylate properly. Regulation of the Epigenome by Vitamin C

this is why high dose vitamin C is used for cancer, and the effect is pretty much the same as using crazy demethylating drugs.

 

[Helen]

@zadig777 Vitamin C enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7

Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
.
Methylation is a copper based process, so demethylation will be done with anything that chelates copper.


SSRI cause serotonin to go up and this forces the body to retain a lot of copper into the brain. to promote MAO A. this causes overmethylation and low HISTAMINE.


I wrote about this many times. thus TEI and ARL says that slow oxidizers are copper toxic.


So I think it is high low copper problem

 

[Rid]

I was listening to some jordan peterson today and I thought something he mentioned was very interesting and relevant to us, and even this thread:

he mentioned how we recently discovered that epigenetic changes happen when you put yourself in new places and new situations. your brain reacts and flips some epigenetic switches. he made the point that staying stagnant can really do some damage, especially to already unhealthy people. I imagine this is another huge aspect as to why many with PFS/PSSD/CFS/PAS etc (can we just make one fucking acronym for all this similar shit like the LQBQ community does? maybe just post-drug? we'll work on it) don't report much progress with their issues. when you have these post-drug issues, it's way harder to live a normal, healthy life, and you can't challenge yourself and keep your brain adaptive and responsive. I commonly see people getting better with travel and adventures. I think we'd all do a lot better with pushing ourselves to the point where we are challenged, and we have these epigenetic switches turned on, but not to the point where we crash. there's obviously a lot of deeper bio shit going on under the surface here, but that's what this comes down to. a lot of post-people get stagnant, and that's a one way ticket to crippling health problems and death.

 

[MNK99]

I identify as fwb lgbtqwerty'xyz i failed genetics but got a double phd in gender studies and manshaming. I am morbidly obese but, big and beautiful. If you look 300 m within my gravitational pull , that is interstellar rape. I have my ACLU lawyers on speed dial in case you ever dare to mansplain things to me like basic details. Hilary was set to be the best president ever but Nixon, Trump, And ' The Russians' Ruined it for everyone. Now my daughter will be forced to use the womens washroom when she grows up. What drugs caused which epigenetic changes that are responsible for my entitlements and this post???

 

[bruschi11]

I was listening to some jordan peterson today and I thought something he mentioned was very interesting and relevant to us, and even this thread:

he mentioned how we recently discovered that epigenetic changes happen when you put yourself in new places and new situations. your brain reacts and flips some epigenetic switches. he made the point that staying stagnant can really do some damage, especially to already unhealthy people. I imagine this is another huge aspect as to why many with PFS/PSSD/CFS/PAS etc (can we just make one fucking acronym for all this similar shit like the LQBQ community does? maybe just post-drug? we'll work on it) don't report much progress with their issues. when you have these post-drug issues, it's way harder to live a normal, healthy life, and you can't challenge yourself and keep your brain adaptive and responsive. I commonly see people getting better with travel and adventures. I think we'd all do a lot better with pushing ourselves to the point where we are challenged, and we have these epigenetic switches turned on, but not to the point where we crash. there's obviously a lot of deeper bio shit going on under the surface here, but that's what this comes down to. a lot of post-people get stagnant, and that's a one way ticket to crippling health problems and death.

Love this.

At home answer for this? Oscillation devices. If you can’t move your body cuz you’re fatigued- just hop on one of these. Google it.

I got one for about $100 on Amazon.