Updated Research and Knowledge - Cutting Edge

[TheKingofFighters]

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.

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)

[SuicidalTraveler]

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.

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)

Yep. Estrogen receptor beta is really great for hair. It's protective. Estrogen receptor alpha is the one that harms the hair and causes gyno. When ER-alpha increased for me, I've gotten a lot more body hair but lost hair on my scalp. I've also developed very mild gyno.

Where have you got your Clomifene citrate?

Are you selling it if you don't use it anymore? Do you have any e-mail from where of I can contact you?

SuicidalTraveler

[TheKingofFighters]

go to HGR

[SuicidalTraveler]

Ok.

[TheKingofFighters]

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

[TheKingofFighters]

On Parkinson's and AGA

17 43,924,219 rs123731246 17q21.31 [SPPL2C]--MAPT MAPT down MAPT down MAPT down 1.930 1.835 <=== this gene is downregulated in balding scalp

Copper results in decreased expression of MAPT mRNA
Copper results in increased phosphorylation of MAPT protein(phosphorylation = silencing, for this gene)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364959/

Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

Abstract
Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10⁻⁹-1.01×10⁻¹²). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10⁻³). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10⁻⁸⁸]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Parkinson's disease is the second most common neurodegenerative disorder with a prevalence of one percent in individuals that are over 60 years old [40]. Despite the often-reported higher prevalence of Parkinson's disease in men, as compared to women [40], there are no previous reports investigating the relationship between AGA and Parkinson's disease. This novel association between Parkinson's disease and early-onset AGA indicated that there could be a shared genetic or environmental cause for both conditions.

[41], although most of the patients affected by drug-induced hair loss are females [41]. As noted above, a greater incidence of Parkinson's disease has been reported in elderly men than in women [40] and androgen mediated neurotoxicity has been proposed to contribute to the gender bias in Parkinson's disease [42]. Since this association is entirely novel, it is unlikely that our results have arisen due to recall bias. In addition, the AGA cases in 23andMe study had an age of onset less than 40 years old. The mean age at diagnosis of Parkinson's disease is 70.5 years [43]. Therefore it is highly unlikely that Parkinson's disease occurred before AGA, as defined in the 23andMe study. At present we are unaware of any prospective Parkinson's disease cohorts having collected AGA data to further explore this relationship, and our evidence provides rationale to undertake such studies.

= Early onset AGA first, then onset of Parkinson's during old age- mostly in men

Ascorbic Acid inhibits the reaction [cyanoginosin LR results in increased phosphorylation of MAPT protein] <== Vitamin C inhibits the silencing of MAPT

Aldehydes results in increased expression of MAPT mRNA <== Alchohols increases MAPT

Estradiol results in increased expression of MAPT protein
Estradiol results in increased phosphorylation of MAPT protein

Caffeine results in decreased phosphorylation of MAPT protein

fulvestrant results in decreased expression of MAPT protein <== Antiestrogens downs MAPT

Ketamine results in increased phosphorylation of MAPT protein <== so balding ketamine abusers should stop for good

Valproic Acid results in increased expression of MAPT

Most antioxidants increases MAPT

[TheKingofFighters]

It also makes sense that Ketamine is bad for hair in AGA individuals because Parkinson's signature symptom is hypolocomotion aka https://en.wikipedia.org/wiki/Hypoactivity (aka 'robot-ification)- something which Ketamine induces

[Anton5redA]

I read this thread about 7 pages back, so TheKingofFighters, it seems like Ethanol is a bad vehicle, Tofacitinib is counter-productive in AGA and Estradiol tends to be absorbed systemically and activates the dormant potential boobies to wake-up and want to see the light of day, but what is it that you would recommend, at this time, for us to use or quit using?

My current topical regimen is: Minoxidil 3%, Finasteride 0.05%, Emu oil, Pygeum Africanum, Litsea Glutinosa, Green Tea extract and Oleuropein all dissolved in water, Ethanol and Propylene Glycol. Plus occasional Ketoconazole every other day.

BTW I noticed more terminal hair over the two months while on this treatment but think that there is just too much in my mix.

[TheKingofFighters]

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?

[TheKingofFighters]

ILMN_1779234 CXCL6 2.176765229
ILMN_2161577 CXCL6 1.772099149
ILMN_1682636 CXCL2 1.421599429
ILMN_1787897 CXCL1 1.001257032
ILMN_1791447 CXCL12 0.452343235
ILMN_1689111 CXCL12 0.424927863
ILMN_1728478 CXCL16 0.298548249
ILMN_1791759 CXCL10 0.291211017
ILMN_1752562 CXCL5 0.212344214
ILMN_1803825 CXCL12 0.205825531
ILMN_2171384 CXCL5 0.118066746

simplified:

CXCL6:

Ascorbic Acid deficiency results in increased expression of CXCL6 mRNA
Ascorbic Acid results in decreased expression of CXCL6 mRNA

CXCL2:

Estradiol affects the expression of CXCL2 mRNA
Estradiol inhibits the reaction [Halothane results in increased expression of CXCL2 mRNA]
Estradiol results in decreased expression of CXCL2 mRNA
fulvestrant inhibits the reaction [Estradiol inhibits the reaction [Halothane results in increased expression of CXCL2 mRNA]

butyraldehyde results in increased expression of CXCL2 mRNA

CXCL16:

lysophosphatidic acid results in increased expression of CXCL16 protein https://en.wikipedia.org/wiki/LPAR6

Valproic Acid results in increased expression of CXCL16 mRNA


CXCL10:

tofacitinib inhibits the reaction [IFNG protein results in increased expression of CXCL10 mRNA]
tofacitinib results in decreased expression of CXCL10 mRNA
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.

Valproic Acid results in increased expression of CXCL10 mRNA

Quercetin results in decreased expression of CXCL10 mRNA <== same goes for Quecertin and Resveratrol- they are double-edged swords.
Quercetin results in decreased secretion of CXCL10 protein

resveratrol results in decreased expression of CXCL10 mRNA
resveratrol results in decreased expression of CXCL10 protein

Ethanol results in increased expression of CXCL10 mRNA

butyraldehyde results in increased expression of CXCL10 mRNA

Estradiol results in increased expression of CXCL10 mRNA
Estradiol results in increased expression of CXCL10 protein

Ascorbic Acid deficiency results in increased expression of CXCL10 mRNA
Ascorbic Acid results in decreased expression of CXCL10 mRNA







CXCL5:

Antirheumatic Agents results in decreased expression of CXCL5 mRNA <== Sulfasalazine and Cox2 inhibitors are some examples. Thus, they are double-edged swords becos they down both pro-hair growth and pro-hair loss chemokine ligands.

Estradiol results in increased expression of CXCL5 mRNA

butyraldehyde results in increased expression of CXCL5 mRNA

Valproic Acid results in decreased expression of CXCL5 mRNA
Valproic Acid results in increased expression of CXCL5 mRNA

On Zinc and the chemokines discussed:

The AGA-downregulated chemokines:

Zinc deficiency results in decreased expression of CXCL12 mRNA

Zinc deficiency results in decreased expression of CXCL10 mRNA

Zinc deficiency results in increased expression of CXCL5 mRNA
Zinc deficiency results in increased expression of CXCL5 protein
Zinc chloride results in increased expression of CXCL5 mRNA
Zinc Sulfate results in increased expression of CXCL5 mRNA

Overall = Zinc upregulates the pro-hair growth inflammatory chemokines

The AGA-upregulated chemokines:

1)Zinc deficiency results in increased expression of CXCL2 mRNA
Zinc Sulfate results in decreased expression of CXCL2 mRNA
Zinc Sulfate results in increased expression of CXCL2 mRNA

2)zinc chloride results in decreased expression of CXCL6 mRNA

'Because CXCL1 and CXCL2 are known to mediate neutrophil influx into tissues (33), we next quantified their mRNA expression in epidermal sheets obtained from ZA and ZD mice after vehicle or CrO application in vivo. Quantitative real-time PCR demonstrated that Zn deficiency resulted in a significant increase of Cxcl1 mRNA 4 and 24 hours after CrO exposure and Cxcl2 mRNA at 4 hours (Figure 3, A and B). The same enhancing effects of Zn deficiency for the chemokine mRNA expression were observed when mice were treated with BAC (Supplemental Figure 5A). In addition, in vitro exposure of Pam-212 keratinocytes to CrO rapidly induced Cxcl1 and Cxcl2 mRNA (Figure 3C). When TPEN was added to the cultures, significant further augmentation of CrO-induced chemokine mRNA accumulation was observed, which was not seen with TPEN alone (Figure 3C). Similar results were obtained in BAC-treated keratinocytes (Supplemental Figure 5B). Furthermore, consistent with recent findings (34), exogenous ATPγS induced Cxcl1 and Cxcl2 mRNA expression by ZA Pam-212 keratinocytes (Figure 3D). Together, our results suggest that Zn deficiency indirectly augments Cxcl1 and Cxcl2 gene expression in CrO-stimulated keratinocytes via increased ATP release, as observed in Figure 2. Interestingly, Zn deficiency further augmented ATPγS-induced Cxcl2, but not Cxcl1, mRNA expression (Figure 3D)'

https://www.jci.org/articles/view/58618

Overall = Zinc downregulates the pro-hair loss inflamamtory chemokines

[TheKingofFighters]

inbeforethecure:

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

[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.

[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

[SuicidalTraveler]

How's it going with UPS?

[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.