Updated Research and Knowledge - Cutting Edge

[InBeforeTheCure]

tofacitinib results in decreased secretion of CXCL10 protein <== I have already trialled Tofacitinib 2 years back. It doesnt work and made my scalp very itchy. a possible reason could be that the Th response was swifted to Th2.

What concentration of tofa did you use?

inbeforethecure:

Im not too sure about minoxidil 'growing hair everywhere' it doesnt seems to have any noticeable results on my scalp at all- while it did help grow my eyebrows

What I mean is that generally, minox has an effect on all types of hair (it causes hypertrichosis), rather than growing hair in one spot and suppressing it in another like sex hormones do.

Inbeforethecure:

helps my gyno. But the problem is while it inhibits DKK1;

Clomiphene results in decreased expression of DKK1 protein

http://ctdbase.org/detail.go?type=chem&acc=D002996&view=ixn

it worsens my hairloss and increased sebum secretion. This stuff agonises/antagonises Estrogen receptors, depending on the tissue. So my guess that it's a very good indicator that Estrogen receptors are deeply involved with AGA.

caused me whole body itch where there's hair- but amazingly, it doesnt seems to bother my scalp. It's an Estrogen receptor Beta agonist. I stopped this becos i switched to Estradiol itself.

If we could avoid systemic absorption of estrogen, that would be nice -- otherwise, it's obviously not viable. Maybe someone should work on formulating something like that.

increased sebum secretion and itch, despite being an anti-inflammatory. My guess tells me that Th response switches are caused by https://en.wikipedia.org/wiki/Cannabinoid_receptor receptors- in the context of AGA. That's why Tofacitinib(i binned it already) didnt work for me. Its about the appropriatehttps://en.wikipedia.org/wiki/Chemokine ligands in the scalp that brings hair growth. misexpress the wrong 1s and AGA occurs(as seen in the diagram u've linked)

inbeforethecure:

If we look@ page 21, there are a few genes that are significantly differentiated between balding and non-balding scalp DPCs:

1)COL18A1 16.750 15.675 <== downregulated in balding scalp when compared to non-balding scalp by more than a whopping 15 fold

Estradiol promotes the reaction [ESR2 protein affects the expression of COL18A1 mRNA]
Estradiol results in increased expression of COL18A1 mRNA

This means the https://en.wikipedia.org/wiki/Estrogen_receptor_beta (aka ESR2) is downregulated in balding scalp. Also, the ESR2 inhibits AR's expression.

2)DHCR7 23.464 20.353 <=== more than 20 fold

Acetaminophen results in decreased expression of DHCR7 mRNA <=== Panadol
Estradiol results in increased expression of DHCR7 mRNA
Caffeine results in decreased expression of DHCR7 mRNA
Copper results in decreased expression of DHCR7 mRNA <== we've got copper toxicity in the balding scalp- and it's 1 of the effectors in Parkinson's
Ethanol results in increased expression of DHCR7 mRNA

3)HTATIP2 6.764 6.038 <== more than 6 fold

Valproic Acid results in increased expression of HTATIP2 mRNA
epigallocatechin gallate results in decreased expression of HTATIP2 mRNA <=== EGCG
Finasteride results in increased expression of HTATIP2 mRNA
Flutamide results in increased expression of HTATIP2 mRNA
Antirheumatic Agents results in decreased expression of HTATIP2 mRNA

4)SCG2 5.365 5.938 <=== more than 5 fold

Valproic Acid results in increased expression of SCG2 mRNA
8-Bromo Cyclic Adenosine Monophosphate results in increased expression of SCG2 mRNA <== cAMP (Bambuterol, Forskolin, etc)

5)COL1A1 5.069 4.926 <=== Collagen type 1, by around 5 fold

Tons of common chemicals ups it

inbeforethecure:

on Stat3:

based on the data from the study regarding the https://en.wikipedia.org/wiki/Chemokine, my opinion is we need the right kind of inflammation to grow hair.

CXCl2 and CXCl6 is probably the 'wrong' type of inflammatory ligands that are upregulated in AGA-affected scalps.

What is ur take on this?

inbeforethecure:

so based on the data, Vitamin C and Zinc would be 2 simple chemicals for aiding hair growth- probably influenicng the ROS pathway.

What I'm looking to do is run a genetic network analysis like the one described in this paper. This will hopefully give us some insight into the complex relationships and help us see what the connections might be; otherwise, it's a nightmare to figure out the relationships among several thousand genes. Most likely they arise from a small subset of interactions.

This is very computationally intensive though, and I'm running into problems because I only have 8GB of RAM.

inbeforethecure:

[FOXO1 protein results in increased expression of SOD2 mRNA]

FOXO1's target gene is SOD2- to remove ROS and improve cell survival. I have read the zebrafish pax1/pax9 study. Like u've mentioned- it states pax1 and Foxo1's interaction increases during hypoxia.

It is highly like due to the 20p11 AGA locus that this interaction is altered- and this is further evident that FOX01's expression is only present in non-balding scalp DPCs

Yeah, if it is PAX1, it's possible that this interaction is where it plays its role, although how it would change FoxO's behavior I have no idea. It could also play a role through its interaction with homeobox genes.

Yeah I agree with you guys. My line of thought is that AGA seems to incorporate oxidative stress too. I don't know for sure though.

@InBeforeTheCure,

Interesting. So what do you guys suggest on a practical level. Do we even have a chance for reversibility or is it a pipe-dream and do we need to work on a preventative level?

Obviously prevention is ideal, but as for some sort of reversal protocol, I don't understand it well enough yet to suggest anything. We still need more data on epithelial signaling networks and so on first. That data isn't available yet, but hopefully will be soon. The new study you linked from the Chew/Philpott group, which I realize now is actually a new study with microarray data from epithelial hair bulbs could be helpful. Also, Rendl should be coming out with some new data on gene expression patterns in mice at different stages of the hair cycle. If we understand it well, then maybe we can "hack" it if possible (which I'd guess probably isn't to any great degree with current technology).

Looking at that box of potentially differential regulated TF's. I see that estrogen interacts with many of those. For example, FOX, HOX, AP-1, SP-1, MYC, AHR.. See; http://press.endocrine.org/doi/full/...0/er.2006-0020.

Senescence would be catastrophic imo. I can see why estrogen would be good in reversing senescence if damage is not too severe though (myc, fos, jun, cyclin d1 etc), in other words making sure the cells re-enter the cell cycle.

If damage is too severe though, it might be irreversible?

After some point, senescent cells undergo irreversible chromatin remodeling, so maybe that's the "point of no return"? One question I have is whether if, under the right circumstances, dermal stem cells can come in and replace the damaged ones. Even a small increase in senescent cells can suppress stem cell activity nearby, so I'd be curious to see what would happen if they were purged. Are the dermal stem cells depleted, or are they just suppressed?

Besides like I mentioned a while ago, the inflammatory aspect of AGA would correlate with SASP the inflammatory phenomena that is a sometimes but not always a hallmark of senescence, and even worse fibrosis which is also a hallmark of senescence which also has been shown in studies for AGA.

There have been several studies associating senescence with AGA like this one; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/.

Yeah, I've read that paper. Kind of interesting too how the cells progressively lose their AR expression. AR is basically a DP signature gene and loses its expression in culture it seems. I suppose like other DP signature genes, it needs epithelial signals to maintain its expression?

To make another example, overexpression of AR for has been associated with oxidative stress too in other studies not related to AGA.

AGA remains a mystery to me though, but it is a b*tch that's for sure.

Mystery is fine. I like a good puzzle.

By the way, I also ran another Opossum gene signature analysis, this time on the top 1000 downregulated genes (maybe that's too many) after 30 minutes of DHT exposure in BAB-A. Several FOX genes showed up at the top (I guess they tend to cluster together because of similar binding sequences or something) and of all the genes that are actually expressed in DPCs, FOXO3 was the highest on the list. This hints again that AR is acting through a non-genomic pathway -- probably mTOR/Akt/SGK -- to interfere with FoxO transcriptional activity. This would expose the cells to bursts of damaging ROS.

[Swooping]

Yeah I agree with you guys. My line of thought is that AGA seems to incorporate oxidative stress too. I don't know for sure though.

@InBeforeTheCure,

Interesting. So what do you guys suggest on a practical level. Do we even have a chance for reversibility or is it a pipe-dream and do we need to work on a preventative level?

Looking at that box of potentially differential regulated TF's. I see that estrogen interacts with many of those. For example, FOX, HOX, AP-1, SP-1, MYC, AHR.. See; http://press.endocrine.org/doi/full/...0/er.2006-0020.

Senescence would be catastrophic imo. I can see why estrogen would be good in reversing senescence if damage is not too severe though (myc, fos, jun, cyclin d1 etc), in other words making sure the cells re-enter the cell cycle.

If damage is too severe though, it might be irreversible?

Besides like I mentioned a while ago, the inflammatory aspect of AGA would correlate with SASP the inflammatory phenomena that is a sometimes but not always a hallmark of senescence, and even worse fibrosis which is also a hallmark of senescence which also has been shown in studies for AGA.

There have been several studies associating senescence with AGA like this one; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/.

To make another example, overexpression of AR for has been associated with oxidative stress too in other studies not related to AGA.

AGA remains a mystery to me though, but it is a b*tch that's for sure.

[forgottenwarrior]

Amalgam is an alloy 50% mercury, which stops elongation of microtubules, which are needed to maintain and grow nerve cells. Sooooo....
It is recommended to take DMSA or IV EDTA immediately prior to and after an amalgam filling extraction so as to avoid Central Nervous System (Headache, poor memory, sleep etc) side effects of the pieces of the filling (microscopic ) going into the stomach and getting absorbed.
Also the dental and cranial nerves suffer from the mercury vapors from drilling etc. but it should pass when mercury gets evenly distributed in the body, but do you really want that?
Not sure why HA is one-sided, maybe you do have a plaque on an artery like Middle Meningeal, that renders that bottleneck ore sensitive to transient bacterial LPS (although LPS is usually vasodilatory), or mercury, who knows? Better go get checked before a clot forms on the bacteria-roughened endothelium (if that is the case of course)

Oh yeah, also, there is more of an urgency to get checked, if you have ever had Rheumatic fever, prosthetic heart valve, or even any foreign surgical material or shrapnel in your body. Or if you have intermittent fevers, unless you are on immunosuppressants. Anyways, take my advice with a grain of salt.

I've noticed since getting my amalgam fillng removed I've had testicular pain, and I noticed my semen become more watery. This was not a good sign at all as this occurred to me in the middle of the day.

I'm very sure the heavy metals from the filling are affecting my hair to some extent. However it's the bacterial side I want to address as well. If I had bacteria clump up around my skull due to the heavy metals what would you believe to be my options?

[SuicidalTraveler]

Ugh. Sorry, I wrote this to the wrong forum. Admin please delete my messages. Thanks.

[SuicidalTraveler]

I have an account. Can't I pay you through PayPal though?

I don't have a credit card really.

[SuicidalTraveler]

Fedex created. Check HGR.

[TheKingofFighters]

I used it for colouring my skin. Induces massive scalp itch.

[TheKingofFighters]

Thanks, I will look at the research for several of these in the Cliff note that are of interest to me, later, after work

So it's:

Estradiol +? + ? in a topical vehicle of Ethanol?% Water?% + Peg40 Castor oil ?% + Polyquaternium-16 ?%(a modified form of K&B solution)

Never Estradiol alone- its just not enough. The vehicle composition is important too because we are gonna need 1 that allows Estradiol to stay in the scalp for as much as possible with minimum amounts going systemic- and keeping ethanol at the bare minimum

[Anton5redA]

Thanks, I will look at the research for several of these in the Cliff note that are of interest to me, later, after work

[TheKingofFighters]

Hi KinfofFighters,

Great, I've read about zinc oxide being used to decrease chronic inflammation and increase rate of healing in macerated skin (pressure ulcers, fresh scars etc). Having Zinc in the mix would probably increase chances of a follicle switching to terminal hair, with stemming from that chemokine production towards the goal of increasing follicle size. I think that the follicle itself needs to be nudged towards the expression and downregulation of genes aimed at increasing the keratin output of each hair follicle.

There is an article (http://www.hindawi.com/journals/ecam/2011/985345/) describing the use of the mixture of liposterolic extract of Serenoa repens (LSESr), its glycoside -( β-sitosterol) and two anti-inflammatory agents (carnitine and thioctic acid) in downregulating the CCL17, CXCL6 and LTB(4) associated with pathways which are involved in the inflammation and apoptosis in and around the AGA hair follicles. This shows that what I am doing, via a different regimen, probably hits the cytokines that you've mentioned, in the appropriate fashion (up or down).

I have observed that the new hair that have sprouted on my scalp over the last month are whisky white for the first 3 mm or so and get thicker and darker towards the base, but are growing at 30-60 degree angles. (different from the old 90-degree hair an inch or two away). I think that happens because dermis there is not thick-enough for their height. Hopefully it will thicken with time. My scalp dermis thinned out because of TNF-Alpha and other chronic catabolic inflammatory markers affecting it for years. (akin to corticosteroidal increase effect on apoptosis of keratinocytes, adipocytes and endothelial cells).

Releasing the downwards pressure of the bad inflammatory factors, both mentioned by you and yet-unrecognized, should allow re-generation of some terminal hair follicles to full capacity, even in the absence of the external up-regulation of pro-anabolic chemokines, as the scalp has some resilience and recoil-pressure to return to its earlier, hairier state.

I am not aware of any substances that would pin-pointedly increase the expression of anabolic genes in the follicle papillae. There are however VEGF-promoters and other bloodflow-increasers via the hypoxia-simulating stimulation, massage and microneedling we can resort to, once the bad inflammation is in check. The latter has been shown to do more for hair thickening than just improve circulation to the scalp.

I am not well-versed in the cell biology, despite a bachelors in the field, so I am not sure of almost everything, the more I learn, the less I know, ha ha. Same thing with medicine, which I have a doctorate in, but if you want to try out something new in growing hair, I might want to look into it.

However, I am not into gynecomastia for example, so estradiol is not gonna get anywhere as high of a concentration as you have tried.

Hi, if im interpreting it right, u're basically asking 'what should i use to regrow hair'.

I would gladly love to help u if i can, but unfortunately- i cant- simply because I do not know the answer myself. Estradiol is only part of the equation and i am still trying to analyse the study(the 1 in discussion here with inbeforethecure) and figure out a solution combo to AGA.

I CAN tell you what NOT to use though. Take note it's just a rough, cliff note I have made myself and there would probably be more changes as time goes on :

Bisphenol A ===> NO, becos it downs MAPT, PLCG2, LZTS1
Copper => NO ===> becos it downs MAPT
Quecertin => NO
Resveratrol => NO
VPA = NO becos it downs VEGFA, LXN
Genistein => NO
Pentanal => NO
Phthalates => NO, becos it downs MAPT, GAS7, NOG, BMP4 and ups FRAP1
Progesterone => NO, becos it downs MAPT, BMP4
PPAR Alpha => NO- becos it downs NOG, DIO2, GUCY1a3, PLCG2, IFI27 and ups FRAP1
PPAR Gamma => NO- becos it downs LXN and ups FRAP1
Calcitriol = NO- becos it downs GAS7, IFI27
cAMP => No- becos it downs BMP4
Finasteride = NO- becos it downs IFI27
Retinoids => NO becos it downs IFI27
Folic acid => becos it downs IFI27
Palm oil => NO becos it downs IFI27 and ups FRAP1
Melantonin => NO becos it ups FRAP1
Zinc = Ambiguous. Downs ARHGEF3

[Anton5redA]

ForgottenWarrior, the pain could also be related to amalgam

Amalgam is an alloy 50% mercury, which stops elongation of microtubules, which are needed to maintain and grow nerve cells. Sooooo....
It is recommended to take DMSA or IV EDTA immediately prior to and after an amalgam filling extraction so as to avoid Central Nervous System (Headache, poor memory, sleep etc) side effects of the pieces of the filling (microscopic ) going into the stomach and getting absorbed.
Also the dental and cranial nerves suffer from the mercury vapors from drilling etc. but it should pass when mercury gets evenly distributed in the body, but do you really want that?
Not sure why HA is one-sided, maybe you do have a plaque on an artery like Middle Meningeal, that renders that bottleneck ore sensitive to transient bacterial LPS (although LPS is usually vasodilatory), or mercury, who knows? Better go get checked before a clot forms on the bacteria-roughened endothelium (if that is the case of course)

Oh yeah, also, there is more of an urgency to get checked, if you have ever had Rheumatic fever, prosthetic heart valve, or even any foreign surgical material or shrapnel in your body. Or if you have intermittent fevers, unless you are on immunosuppressants. Anyways, take my advice with a grain of salt.

[Anton5redA]

Hi KinfofFighters,

Great, I've read about zinc oxide being used to decrease chronic inflammation and increase rate of healing in macerated skin (pressure ulcers, fresh scars etc). Having Zinc in the mix would probably increase chances of a follicle switching to terminal hair, with stemming from that chemokine production towards the goal of increasing follicle size. I think that the follicle itself needs to be nudged towards the expression and downregulation of genes aimed at increasing the keratin output of each hair follicle.

There is an article (http://www.hindawi.com/journals/ecam/2011/985345/) describing the use of the mixture of liposterolic extract of Serenoa repens (LSESr), its glycoside -( β-sitosterol) and two anti-inflammatory agents (carnitine and thioctic acid) in downregulating the CCL17, CXCL6 and LTB(4) associated with pathways which are involved in the inflammation and apoptosis in and around the AGA hair follicles. This shows that what I am doing, via a different regimen, probably hits the cytokines that you've mentioned, in the appropriate fashion (up or down).

I have observed that the new hair that have sprouted on my scalp over the last month are whisky white for the first 3 mm or so and get thicker and darker towards the base, but are growing at 30-60 degree angles. (different from the old 90-degree hair an inch or two away). I think that happens because dermis there is not thick-enough for their height. Hopefully it will thicken with time. My scalp dermis thinned out because of TNF-Alpha and other chronic catabolic inflammatory markers affecting it for years. (akin to corticosteroidal increase effect on apoptosis of keratinocytes, adipocytes and endothelial cells).

Releasing the downwards pressure of the bad inflammatory factors, both mentioned by you and yet-unrecognized, should allow re-generation of some terminal hair follicles to full capacity, even in the absence of the external up-regulation of pro-anabolic chemokines, as the scalp has some resilience and recoil-pressure to return to its earlier, hairier state.

I am not aware of any substances that would pin-pointedly increase the expression of anabolic genes in the follicle papillae. There are however VEGF-promoters and other bloodflow-increasers via the hypoxia-simulating stimulation, massage and microneedling we can resort to, once the bad inflammation is in check. The latter has been shown to do more for hair thickening than just improve circulation to the scalp.

I am not well-versed in the cell biology, despite a bachelors in the field, so I am not sure of almost everything, the more I learn, the less I know, ha ha. Same thing with medicine, which I have a doctorate in, but if you want to try out something new in growing hair, I might want to look into it.

However, I am not into gynecomastia for example, so estradiol is not gonna get anywhere as high of a concentration as you have tried.

[SuicidalTraveler]

How's it going with UPS?

[TheKingofFighters]

Estradiol results in increased activity of SOD2 protein
Estradiol results in increased expression of and results in increased activity of SOD2 protein
Estradiol results in increased expression of SOD2 mRNA
Estradiol results in increased expression of SOD2 protein

inbeforethecure:

[FOXO1 protein results in increased expression of SOD2 mRNA]

FOXO1's target gene is SOD2- to remove ROS and improve cell survival. I have read the zebrafish pax1/pax9 study. Like u've mentioned- it states pax1 and Foxo1's interaction increases during hypoxia.

It is highly like due to the 20p11 AGA locus that this interaction is altered- and this is further evident that FOX01's expression is only present in non-balding scalp DPCs

[forgottenwarrior]

I've read this thread and can certainly say that zinc plays a big role in androgen metabolism along with the expression of estrogen receptors.

http://www.ncbi.nlm.nih.gov/pubmed/8613886

We studied the effects of zinc deficiency on hepatic androgen metabolism and aromatization, androgen and estrogen receptor binding, and circulating levels of reproductive hormones in freely fed, pair-fed and zinc deficient rats. Hepatic conversion of testosterone to dihydrotestosterone was significantly less, but formation of estradiol from testosterone was significantly greater in rats fed the zinc-deficient diet compared with freely fed and pair-fed control rats. There were significantly lower serum concentrations of luteinizing hormone, estradiol and testosterone in rats fed the zinc-deficient diet. No difference in the concentration of serum follicle-stimulating hormone was observed between the zinc-deficient group and either control group. Scatchard analyses of the receptor binding data showed a significantly higher level of estrogen receptor in zinc-deficient rats (36.6 +/- 3.4 fmol/mg protein) than in pair-fed controls (23.3 +/- 2.2 fmol/mg protein) and a significantly lower level of androgen binding sites in rats fed the zinc-deficient diet (6.7 +/- 0.7 fmol/mg protein) than in pair-fed control rats (11.3 +/- 1.2 fmol/mg protein). There were no differences in hepatic androgen and estrogen receptor levels between freely fed and pair-fed controls. These findings indicate that zinc deficiency reduces circulating luteinizing hormone and testosterone concentrations, alters hepatic steroid metabolism, and modifies sex steroid hormone receptor levels, thereby contributing to the pathogenesis of male reproductive dysfunction.


This is not to say Zinc is bad at all but rather, needed to keep masculinity in check for us men and prevent gyno and other unwanted effects from estradiol.

The other thing I wanted to bring up to attention was the possibility of microbes altering estrogen and androgen metabolism.

http://immortalhair.forumandco.com/t9616-dental-work-stopped-my-hair-loss

I've recently had dental work done, and will continue to do so as I'm not satisfied with the filling I was given since headaches have been continually plaguing me. They occur only on the side where the amalgam filled tooth was.

I would like to expand on the pathogen possibility later with how gut flora can influence hormones and such.