Updated Research and Knowledge - Cutting Edge

[lukey]

Thanks for the all the work Chemical and Brianboy. Ive purchased the supplies and keen to start soon.

Im already using seti in an etch/pg solution so keen to not add too much more ethanol to my scalp each day. That said, I want to ensure proper delivery to the follicles.

I have DMSO as well. Would a water/eth/pg/dmso be a good idea? What ratios are you both using?

I don't have any Keto to hand but I have some Dexamethasone, which apparently raises PGE2 and is an AA. Would adding that to the mix be too much? I see that you put your Keto on in the morning. Important to use it hours before the EGCG/OL mix?

How are you getting on with seti?

[inbrugge]

I'm not too familiar with the efficacy OC versus seti. I cant really comment on its topical vs oral intake effectiveness either. I dont see it being a huge problem taking it orally given that it doesnt interact with PGD2 itself, but I'm not a fan of systemic usage.



It could work but if does increase hair then you'd notice hair everywhere. OL and EGCG work differently when taken orally and I cant vouch for their oral effectiveness on hair growth. Theres not alot of research on oral supplements increasing scalp hair growth in AGA unfortuneately. You're much better off using them topically since they are quite soluble and have low-ish molecular weights.



Good question. Simply dissolving in a solution does not mean it will permeate the skin. The molecular weight in addition to solubility properties are a much predictor of topical absorption. This is a probabilistic model where complete absorption and equal tissue distribution is not guaranteed. Ethanol has the ability to strip the skin of lipids and enhance the absorption of molecules. Heres a post I made on minox/OL molecular weight and absorption.

http://www.ncbi.nlm.nih.gov/pubmed/22024172

I apologise, you are correct. It is indeed the DP1, so CRTH2 anatagonists shouldnt be a problem. I think I need you to correct mistakes in my analysis lol.



Two receptors for EDA were found that are specific for the two isoforms EDA-A1 and EDA-A2: EDAR and EDA2R, respectively. EDA-A1 and its receptor EDAR are capable of activating the NF-κB pathway and are implicated in hair growth. EDA2R is capable of activating the NF-κB pathway and also through TRAF3,6, JNK (c-Jun N-terminal kinase), which activates c-Jun. Mutations in EDA and EDAR give rise to ectodermal dysplasia, a clinical syndrome characterized by loss of hair, sweat glands, and teeth, whereas mutations in EDA2R do not. Recently, a preliminary report suggested that EDAR may influence hair thickness in Asians, A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.

EDA2R could influence the onset of AGA through the activation of the NF-κB pathway or by c-Jun, which has been shown to be critical for AR transactivation. Moreover, in adult mice, EDA2R is also expressed in the hair bulb and in differentiating hair matrix (Botchkarev and Fessing, 2005).



Indeed, its the EDA2R that is involved in AR transactivation. But the EDAR variant also activates nf-kb without negative effect on hair. It seems theres alot genes that can influence the AR and transactivation of AR via different mechanisms leading to increased nuclear translocation. A combination of these alleles that enhance AR be it subtly or directly, definitely have the ability to predispose individuals to AGA. The nf-kb pathway seems to have differential effects depending on its mechanism of activation? I think I'm missing something that doesnt explain why EDAR can increase hair thickness.




So this means in the presence of AR, anything that wants to activate AKT via PI3K will be unsuccessful. This includes IGF-1, shh, EGF (wiki). Beautiful diagram here: https://en.wikipedia.org/wiki/File:M...thway-v1.7.svg

But does this mean beard DPC do not inhibit PI3K via PTEN in response to AR activation? Apparently PTEN deficiency results in accelerated hair follicle morphogenesis and enhanced AKT(PKB) activation (study). Very interesting.

Heres some more research on ERb and hair.



So in females, ERb increases frontotemporal hair growth but inhibits in other areas?



Studies say that estrogen prolongs anagen but inhibits hair shaft elongation (in females). Perhaps ERb in the ORS is inhibiting proliferation, but ERa in the DPC is maintaining BetaCatenin. But Estrogen acts differently in frontotemporal regions? Females have a differential scalp response phenotype. Males start off as females in the womb, so what if Androgens exploit this localised response in a detrimental manner? This sets off the chain reaction whereby follicles release DKK-1 and TGF-Beta into the ECM affecting nearby follicles that arent fully susceptible to AR's effects.

Anyways, I want to know what role ERa has in male DPC. ERb can increase proliferation of existing hair, but does it secrete growth factors in a paracrine manner? Or does ERa promote WNT activation by itself in DPC to prolong anagen?



It can! This is excellent research SriHanuman. Unfortuneately I cant use this because I'm trying a different stack, so I wont be able to gauge its effectiveness. People who cant use minox might find fo-ti useful.



Thank you! We're uncovering so much research that I think it is already leading to something.

Update

Last week I increased the EGCG concentration totalling 12.5mg/ml. The hairs that I grew using minox + OL are 100% terminal. Really wasnt expecting results this fast. I'm seeing more tiny vellus hairs along nw1 hairline and the skin turning grey/green. My nw1/0 hairs grow sideways, as in they come out of the skin at very low degree angles. My nw0 is hairline is completely bald atm so it might be harder to regrow. I'm not sure if my aggressive micro-needling (3mm derma pen) last year has caused scarring. I hope not because I'd be devastated.

Bear in mind I'm using the MXOLCG once a day at night because of work and laziness, and Ketoconazole in the morning. During the weekends I use MXOLCG 3x day. If only I could use minox 3x a day everyday... I try to use Emu oil every two days, and I'll be adding the Gamma Linoleic Acid to the Emu oil (which has minox in it already). I'll be posting pics soon. I am tempted to use Rosemary but I'll wait.

I'm also going to ask the moderators to let me edit my first post so I can reorganise the research for people to find easily.

Any pictures Chemical?

[ryan82]

Chemical , Can you please tell me how much EGCG and OL pills you are now using in a 60 MG bottle of minox ? I was dumping in one EGCG pill and a half pill of OL . Can you update the mix ?

I want to know also! What must i buy for same regime. ??

[InBeforeTheCure]

I apologise, you are correct. It is indeed the DP1, so CRTH2 anatagonists shouldnt be a problem. I think I need you to correct mistakes in my analysis lol.

A rare occurrence, I'm sure, since your knowledge of these things far exceeds mine, as I'm a noob to this material.

Indeed, its the EDA2R that is involved in AR transactivation. But the EDAR variant also activates nf-kb without negative effect on hair. It seems theres alot genes that can influence the AR and transactivation of AR via different mechanisms leading to increased nuclear translocation. A combination of these alleles that enhance AR be it subtly or directly, definitely have the ability to predispose individuals to AGA. The nf-kb pathway seems to have differential effects depending on its mechanism of activation? I think I'm missing something that doesnt explain why EDAR can increase hair thickness.

The EDAR variant associated with greater hair thickness in Asians is the one that reduces Nf-kB, not increases it.

Interestingly, the C allele that was associated with thicker hair showed lower relative luciferase activities than the T allele in both the cell lines. These results indicated that the amino acid replacement in the death domain causes a functional change and results in the lower activity of NF-κB. Although the relation between NF-κB activation level and hair thickness has not been clear, it has been reported that steroid induces NF-κB suppression as well as hair regrowth (21,22), which supports that the lower NF-κB level may be associated with higher activity of hair formation.

So this means in the presence of AR, anything that wants to activate AKT via PI3K will be unsuccessful. This includes IGF-1, shh, EGF (wiki). Beautiful diagram here: https://en.wikipedia.org/wiki/File:M...thway-v1.7.svg

But does this mean beard DPC do not inhibit PI3K via PTEN in response to AR activation? Apparently PTEN deficiency results in accelerated hair follicle morphogenesis and enhanced AKT(PKB) activation (study). Very interesting.

Who knows? Is anyone familiar with any research about differences in the way AR works within the cycling of head hair vs. the cycling of facial hair?

Heres some more research on ERb and hair.



So in females, ERb increases frontotemporal hair growth but inhibits in other areas?



Studies say that estrogen prolongs anagen but inhibits hair shaft elongation (in females). Perhaps ERb in the ORS is inhibiting proliferation, but ERa in the DPC is maintaining BetaCatenin. But Estrogen acts differently in frontotemporal regions? Females have a differential scalp response phenotype. Males start off as females in the womb, so what if Androgens exploit this localised response in a detrimental manner? This sets off the chain reaction whereby follicles release DKK-1 and TGF-Beta into the ECM affecting nearby follicles that arent fully susceptible to AR's effects.

Anyways, I want to know what role ERa has in male DPC. ERb can increase proliferation of existing hair, but does it secrete growth factors in a paracrine manner? Or does ERa promote WNT activation by itself in DPC to prolong anagen?

Frontotemporal = temples? But balding can start at the vertex as well in some cases. Paracrine signals may still play a role though and contribute to feedback loops in nearby follicles though, I assume.

By the way, this was posted in another thread: Mapping out cell conversion -
Algorithm takes the field of cell reprogramming forward.

Link to the software: http://www.mogrify.net/

Dermal papilla cell to hair follicle cell (do they mean hair follicle epithelial cells?):



Hair follicle cell to dermal papilla cell:



Interesting how EBF1 is involved in mesenchymal -> epithelial proliferation, while VDR and NFKB1 are involved in epithelial -> mesenchymal transition. (this all assuming "hair follicle cell" = epithelial cell; maybe it means undifferentiated cells -> hair follicle cells or something, as opposed to feathers, scales, normal skin cells, etc.)

And another systems biology paper I came across recently, which may or may not be helpful, but is certainly interesting: Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators

Abstract:

The hair cycle is a dynamic process where follicles repeatedly move through phases of growth, retraction, and relative quiescence. This process is an example of temporal and spatial biological complexity. Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research. Currently, a systematic characterization of gene expression and summarization within the context of a mathematical model is not yet available. Given the cyclic nature of the hair cycle, we felt it was important to consider a subset of genes with periodic expression. To this end, we combined several mathematical approaches with high-throughput, whole mouse skin, mRNA expression data to characterize aspects of the dynamics and the possible cell populations corresponding to potentially periodic patterns. In particular two gene clusters, demonstrating properties of out-of-phase synchronized expression, were identified. A mean field, phase coupled oscillator model was shown to quantitatively recapitulate the synchronization observed in the data. Furthermore, we found only one configuration of positive-negative coupling to be dynamically stable, which provided insight on general features of the regulation. Subsequent bifurcation analysis was able to identify and describe alternate states based on perturbation of system parameters. A 2-population mixture model and cell type enrichment was used to associate the two gene clusters to features of background mesenchymal populations and rapidly expanding follicular epithelial cells. Distinct timing and localization of expression was also shown by RNA and protein imaging for representative genes. Taken together, the evidence suggests that synchronization between expanding epithelial and background mesenchymal cells may be maintained, in part, by inhibitory regulation, and potential mediators of this regulation were identified. Furthermore, the model suggests that impairing this negative regulation will drive a bifurcation which may represent transition into a pathological state such as hair miniaturization.

They use a modified version of the Kuramoto model to model the hair cycle. Such models of coupled oscillators have been used to model other biological systems before.

Mesenchymal (dermal papilla) cells are positively coupled and epithelial cells are negatively coupled.





A high proportion of positively coupled oscillators (as opposed to negative ones) leads to a synchronized and stable state. As this proportion gets lower, the system is kicked into a different state of rapidly cycling, miniaturized hair. As p gets even lower, the system becomes totally decoherent - physically, this would correspond to continuous quiescence, I think.

[Seuxin]

Hello guys,

What about this Oleuropein 40% source ? : http://www.skinactives.com/Oleuropein.html
0.6g -> 1.76€ !

[Chemical]

HEY Chemical thank you for what are you doing.

Can you do a summarise of your invention, like what exactly to use( what products it contains) , the concentration ,and how often to use like instructions on drughs???

I will update the first post with all this information, for now you can go through my recent posts here.

Chemical , Can you please tell me how much EGCG and OL pills you are now using in a 60 MG bottle of minox ? I was dumping in one EGCG pill and a half pill of OL . Can you update the mix ?

Right now I'm using ~12mg/ml EGCG and around 0.5-1mg/ml of OL.
I found out EGCG's max solubility in EtOh is 20mg/ml. I think I read somewhere kirkland minox is 70% ethanol, so if thats true then the minox is saturating the ethanol a bit. And the OL is too, reducing the maximum saturation of EGCG. I noticed the EGCG leaving residue, and I can literally peel it off after a day or so. Not sure if that could be increased keratinocyte turnover? So for my next mix I'm going to use only 2 x EGCG caps = 300mg EGCG (actual) in 30ml. If it still leaves a residue I'll dilute further. I'm probably going to use 1/4 cap of OL in 30ml.

Anyway I remember you said you don't take any anti DHT. According to you new hairs get thicker and potentially hold on thanks to EGCG but what about existing hair ? Do you apply the solution all over the scalp or only at temples ? Thanks for keeping us updated!

Yes taking an oral DHT blocker will only increase endogenous testosterone to compensate the feedback loop. You'll have a marginal decrease in DHT but a moderate elevation in T. Not worth it imo. You're better off using non systemic 5ar inhibitors with an AR antagonist of some sort.

My existing occipital hairs and regions beside the hairline are getting alot thicker and longer. Shedding is like 10 hairs per day. Minox is known to do this and I fully suspect its minox. Regrowth is what we're looking out for.

I'm already using seti in an etch/pg solution so keen to not add too much more ethanol to my scalp each day. That said, I want to ensure proper delivery to the follicles.

I have DMSO as well. Would a water/eth/pg/dmso be a good idea? What ratios are you both using?

I don't have any Keto to hand but I have some Dexamethasone, which apparently raises PGE2 and is an AA. Would adding that to the mix be too much? I see that you put your Keto on in the morning. Important to use it hours before the EGCG/OL mix?

I think alot of people are curious to know - Any progress with Seti?
I'm on the fence about DMSO. There are reports it increases shedding when used as a vehicle so just to be on the safe side, skip it.

Heres what BRIAN is using.

I wouldnt advocate dexamethasone. Its quite a strong corticosteroid and from my understanding it shouldnt be used off-label for anything other than reducing severe inflamation or skin conditions.

I want to know also! What must i buy for same regime. ??

Just because I've seen results does not mean you will too. This is still experimental and for all we know my results could very well be just minox. You should make this decision after careful consideration because you'll only set yourself up for disappointment if you start thinking this is a one size fits all protocol. I'll edit first post with info.

The EDAR variant associated with greater hair thickness in Asians is the one that reduces Nf-kB, not increases it.

The 1540T/C polymorphism is located in the death domain, that is, the intracellular domain necessary to interact with EDAR-binding death domain adapter protein, EDARADD. It is known that EDAR/EDARADD interaction results in the activation of the downstream transcription factor NF-κB, and this molecular pathway plays a key role in formation of hair placode. Therefore, a possibility is that 1540T/C affects the NF-κB activity through an altered efficiency of interaction between EDAR and EDARADD. To compare the 1540T and C alleles in the ability of NF-κB activation, we performed luciferase assays using HeLa and 293A cells. These cells were transfected with EDAR expression vectors carrying each allele (pEF1-EDAR-1540T and pEF1-EDAR-1540C), reporter plasmids with the luciferase gene under control of the five NF-κB promoter elements, and internal control vectors. The NF-κB/luciferase activities were compared among 1540T, 1540C and 1540T+C (artificial heterozygote). We observed significant differences in relative luciferase activities between 1540T and 1540C (t-test: HeLa cell P = 5.7 × 10−3, 293A cell P = 1.9 × 10−5) and between 1540T and 1540T+C (293A cell P = 5.8 × 10−5) (Fig. 5). Interestingly, the C allele that was associated with thicker hair showed lower relative luciferase activities than the T allele in both the cell lines. These results indicated that the amino acid replacement in the death domain causes a functional change and results in the lower activity of NF-κB.

Inhibition of nf-kb or reduced nf-kb activation?

This study says that nf-kb activity is necessary for anagen...

Frontotemporal = temples? But balding can start at the vertex as well in some cases. Paracrine signals may still play a role though and contribute to feedback loops in nearby follicles though, I assume.

The figure in this study shows pictures of "frontotemporal" hairloss exactly like the signature norwood pattern, so the AGA pattern is indeed in females too but actually enhances hair growth. I cant explain the vertex thinning though.

Interesting how EBF1 is involved in mesenchymal -> epithelial proliferation, while VDR and NFKB1 are involved in epithelial -> mesenchymal transition. (this all assuming "hair follicle cell" = epithelial cell; maybe it means undifferentiated cells -> hair follicle cells or something, as opposed to feathers, scales, normal skin cells, etc.)

I'm going to read that study you linked.

I realise I was being stupid. The original study that mentioned EBF1 shows that EBF1 regulates the Adipocyte precursor lineage, and also controls PDGF-A:

PDGFR is activated in the DP and the lower part of the hair germ (Figure 6E). To determine if intradermal adipose regeneration is required for activation of the PDGFR, we analyzed hair follicles from BADGE-treated and Ebf1 null mice for activation of the PDGFR at P21. As seen in Figure 6E, PDGFR activation was diminished in the DP of both BADGE-treated and Ebf1 null mice.

In an earlier post I went over how PDGF signalling induces hair canal formation and subsequent anagen induction: here.

On a separate discussion, I found this study:


Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells.

This supports the notion that anti-oxidants/ROS scavengers can reduce TGF-Beta.

More importantly though!

http://imgur.com/a/rdWnB

[TheKingofFighters]

hey Chemical do u have an email address i can contact u with?

[tiktok]

Those results are very interesting. Looking forward to seeing the future progress!

[burtandernie]

So your of the opinion that RU is better than using fin? The big issue is there arent any good AR antagonists or no one would be using fin still. I mean we have known androgens cause MPB for like 20 or 30 years yet still have no real way to actually do anything about that. There is no practical way to stop androgens non systemically even still

"Yes taking an oral DHT blocker will only increase endogenous testosterone to compensate the feedback loop. You'll have a marginal decrease in DHT but a moderate elevation in T. Not worth it imo. You're better off using non systemic 5ar inhibitors with an AR antagonist of some sort. "

[scooterboy]

So your using 4 x EGCG caps and 1 half OL cap in 60MLS of minox .

[Swooping]

What is your background Chemical? Doing any work/study related to biology? Or just pure interest.

[Seuxin]

Hello Guys'

I'm planning to coumpound a custom cream for my temples. ( Cream is better to use with a lot of shit).

I'm thinking about :

-Adenosine (high amount like 5%)
-Baicailin
-Vitamin B6
-Zinc Sulphate
-Oleuropein high dosed (0.6gr in a 4oz cream jar)
-ECGC (-> Don't really know if usefull since oleuropein is antioxydant)
-Saw Palmetto
-Vitamin E Succinate ( cause an increase of PGE2)
-KGF (Keratinocyte Grow Factor) ( 50mcg)

--> What do you think ? Any advice ?

Thanks.

[bluesuedeshoes]

To those that have asked about a seti update...only been using for a few weeks so too early to make any sort of decent appraisal. My vehicle isnt ideal - etc/pg. I have noticed a slight reduction of the itch but that's really it. The people who have had some sort of success on other forums with seti have been using a custom vehicle.

[potato1987]

I m really interessed in your pictures Chemical. I would not judge sth before at least 2 months. Sounds really good. But is it not also possible that with your consequent usage of minox it can be its effect alone? Do you preclude that completely? Looking forward too your pictures soon then if you see its effects already go ahead

Any joy with the custom stuff mate? I can't touch fin or minox so would be great to have a pre mix of natural components.

[ryan82]

To those that have asked about a seti update...only been using for a few weeks so too early to make any sort of decent appraisal. My vehicle isnt ideal - etc/pg. I have noticed a slight reduction of the itch but that's really it. The people who have had some sort of success on other forums with seti have been using a custom vehicle.

What is that custom vehicle?