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Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Wed Oct 24, 2018 1:41 pm
by TalkingAntColony
Regarding decitabine, it appears to work on cells in the s phase of their cycle. The s phase of the cell cycle is when the cell creates an extra copy of its DNA. After the s phase is mitosis, or cell division.

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Molecular Pharmacology of Decitabine
decitabine belongs to the family of S-phase-specific drugs, meaning that it is only active when incorporated in the DNA of cells in the S-phase of the cell cycle. The S-phase specificity enables selective and effective incorporation of decitabine into the DNA of rapidly dividing cancer cells, reducing, thereby, demethylation effects in normal cells which have a slower replicating rate.


Cells in the human body have different cell cycle lengths. Some cells stop dividing altogether, like neurons. For decitabine to effect them, it would need to occur during their s phase of the cell cycle. See this article for human cell cycle lengths:

http://book.bionumbers.org/how-quickly- ... hemselves/

What is worrying about decitabine, is that it gets incorporated into cell DNA. If this happens to normal cells, they might be permanently changed in a bad way. I havent found any side effect analysis that explores this, as it seems most people tolerate it, but then again they are facing death via cancer so are less worried about side effects. If anyone has more info on side effects, please post it here.

On taking HDAC inhibitors and DNMT inhibitors simultaneously:
Hypomethylating Agents in Combination With Histone Deacetylase Inhibitors
In that study, patients received azacitidine for 10 days plus entinostat on days 3 and 10. Azacitidine requires active cell cycling, because it is incorporated into DNA during the S-phase of the cell cycle. HDAC inhibitors like entinostat are potent cell-cycle inhibitors, and concomitant administration of an HDAC inhibitor with azacitidine can lead to less effective changes in promoter methylation. This hypothesis was supported by genomewide DNA methylation studies demonstrating that DNA methylation was significantly less pronounced in patients who received combined azacitidine plus entinostat compared with those who received zacitidine alone.24


HDAC inhibitors are seeing a role in diabetes treatment. This is interesting to me because I've felt that I have had less tolerance to carbs with PSSD, even measuring prediabetic blood sugar levels occasionally, although I generally stick to a low carb diet now. If HDAC inhibitors are helping PSSD symptoms, perhaps one of the mechanisms could be through metabolic regulations. If levels of naturally occurring HDAC inhibitors (such as those generated by gut bacteria) are reduced in PSSD, this could be relevant.

Improving Insulin Sensitivity With HDAC Inhibitor
HDAC3 inhibition has been shown to restore PPARγ function in obesity (8,15). In one study, two pan-HDAC inhibitors, sodium butyrate and TSA, were supplemented to block HDAC3 activity in DIO mice. The treatment generated a set of unexpected metabolic effects including increased energy expenditure, reduction in adipose tissue expansion, resistance to obesity, and prevention of insulin resistance....In the glucose metabolism pathway, acetylation regulates gluconeogenesis (23), glycolysis, glycogenesis, and glucose oxidative metabolism (1). In the fatty acid and amino acid metabolism pathways, acetylation regulates β-oxidation and urea cycle (22). Concentration of glucose, fatty acids, and amino acids determines the acetylation of metabolic enzymes. TSA was shown to regulate the metabolism through protein acetylation in the cytosol in those studies.


Histone deacetylase inhibitors: Future therapeutics for insulin resistance and type 2 diabetes
The long-term treatment with valproate is associated with weight gain and hyperinsulinemia... Verrotti and co-workers demonstrated that hyperinsulinemia and insulin resistance occurred only in those epileptic patients who were obese and not in non-obese epileptic patients, following 1 year of valproate treatment... Based upon the results obtained in number of preclinical studies, there is no doubt that HDACs regulate insulin signalling pathways and glucose utilization

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Wed Oct 24, 2018 2:27 pm
by TalkingAntColony
Epigenome targeting by probiotic metabolites
Genetic analysis of probiotic effects following treatment of healthy adults with L. casei and L. rhamnosus revealed upregulation of several key mucosal immune response genes.... Levels of SCFA have been demonstrated to be reduced in inflammatory diseases, possibly as a result of an altered gut microbiota...probiotic supplementation could restore SCFA levels by modulating the microbial environment..., the principal HDACi compound is butyric acid (sodium butyrate) which inhibits most HDAC enzymes except class III and class II HDACs 6 and 10...treatment of mice with F. prausnitzii led to a shift in microbiota composition, reduced inflammatory cytokine levels such as IL-2... The anti-inflammatory effects of SCFA-producing probiotic bacterium was further illustrated with Propionibacterium freudenreichii, which was found to shift the extracellular pH from 7.5 to 5.5 in the colon and was related to levels of the SCFAs, acetate and propionate...We believe that the biological activity of probiotics are mediated through complex epigenetic changes that regulate the activation status of key transcription factors involved in host immunity.


Interesting connection between gut bacteria and epigenetic regulation. Also, IL-2 was seen to increase, along with changes to gut microbiota, in mice post-finasteride in another study I posted here. SSRI's could have similar effects, suggesting F. prausnitzii and other probiotics could be of interest to us.

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Wed Oct 24, 2018 4:46 pm
by Dead
TalkingAntColony wrote:
Curcumin is a potent DNA hypomethylation agent

"curcumin can induce about 15–20% decrease of global DNA methylation level"

Anyone tried taking high dose curcumin? If i read the study right it seemed to be more effective than decitabine.

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Thu Oct 25, 2018 12:20 am
by anacleta
Food that shapes you: how diet can change your epigenome
https://www.scienceinschool.org/2014/issue28/epigenetics

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Thu Oct 25, 2018 8:06 am
by Trazohell
I tried curcumin two months, 1 g per day. Before PSSD it make me very horny, sperm was better and more on it after PSSD begin.
Maybe I should take it longer or valporate, would be so friendly and answer me nasilibi?

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Fri Oct 26, 2018 7:26 am
by TalkingAntColony
To find more studies on epigenetic modification, check out fetal hemoglobin (HbF). HbF is a form of hemoglobin (Hb) that exists in fetal blood and babies up to a few months old. HbF has stronger affinity for oxygen, which allows a fetus to pull oxygen off its mother's Hb. HbF is not needed after birth, so the body downregulates/silences those genes epigenetically. HbF is sometimes seen in adults taking epigenome-modifying drugs like DNMT inhibitors and HDAC inhibitors. Sickle cell anemia can be helped by re-expressing HbF, so there are interesting clinical trials on sickle cell patients using these types of drugs. In some cases, cycles of hypomethylating drugs result in permanent increases in HbF, suggesting their epigenome has been persistently modified. Although it is more common to see HbF levels fall dramatically within weeks after cessation of hypomethylating drugs, suggesting that often not enough cells are modified for the epigenetic modifications to stick.

Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia.

2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia.

Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Thu Nov 08, 2018 1:52 pm
by nasibi
RT inhibitors like Nevirapine have been shown to modulate gene expression. They have been shown to not only turn ON various silenced genes including the androgen receptor (AR) gene, but also restore androgen signaling. This may result in responding to androgens like Testosterone and DHT once again, which may improve sexual function.

https://onlinelibrary.wiley.com/doi/abs ... pros.20923

They have also been shown to reverse gene silencing post transcriptionally by downregulating the expression of miRNA. It may cause liver damage though.

https://www.google.de/url?sa=t&source=w ... 1hTVWbqrMS

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Sat Nov 17, 2018 2:31 am
by scripy3
Please tell where to order the anti hiv in europe

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Thu Nov 29, 2018 3:44 pm
by londonexec
zadig777 wrote:hes using emitricibine/tenofovir,the green one from this site
https://www.purchase-prep.com


i used to get mine from here too, but seems like their site is having lots of issues lately... order from https://getpreponline.com now and haven't had any problems getting it on time

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Apr 02, 2019 8:02 am
by PsychoGenesis
londonexec wrote:
zadig777 wrote:hes using emitricibine/tenofovir,the green one from this site
https://www.purchase-prep.com


i used to get mine from here too, but seems like their site is having lots of issues lately... order from https://getpreponline.com now and haven't had any problems getting it on time
so does it work?