Updated Research and Knowledge - Cutting Edge

[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.

[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:

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?

[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]

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

[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]

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

[SuicidalTraveler]

Ok.

[TheKingofFighters]

go to HGR

[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]

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)

[TheKingofFighters]

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

raw powder is a conventional, slightly bitter-tasting form

BTW, I should mention that SARMS like Ostarine still causes hairloss despite 'not affecting non-muscle tissues'. Perhaps muscle layers in the scalp are a factor to AGA? It gves me scalp itch everytime i use it:

helps alleviate oxidative stress- but it stop b-catenin. So again, ROS is defnitely a factor in AGA.
B2 adrenaagic agonists like Bambuterol are VERY anabolic(via cAMP upregulation). But I found that the more buffed up i became- the more hair i loss. and as mentioned before. Im not too sure about this 1 on whether it's helping or causing hairloss.

WORSENED my hairloss- it also gave me body odour and severe scalp itch. Something about the GABA receptors as well. It could be the N type voltage-gated calcium channels involved too.

[TheKingofFighters]

Estradiol:





The powder is not in a conventional 'powdery' form- it's in a crystaline state that resembles table sugar

[TheKingofFighters]

the angle im looking at is there must be some causative ROS-related gene(s) deficient in AGA that work(s) hand-in-hand with Estradiol(which we are already lacking in) to grow hair.

So it's Estradiol + ? =hair. Estradiol by itself is not enough. I have 1 gram of it in my fridge(and the dosage is in the mcgs/ml of vehicle).

I have not seen appreciable results 1 despite trying it out for weeks. It brings on numerous sides like gyno- though IMO, i assume this has something to do with the vehicle itself that results in more systemic penetration instead of remaining in the scalp.

[TheKingofFighters]

Another ROS scavenger and FoxO target gene is SOD2. There are three SOD2 transcripts, and all three are underexpressed in balding DPCs (47.2%, 28.7%, and 27.0% expression compared to non-balding DPCs in untreated cells).

ILMN_2336781 SOD2 0.472452155
ILMN_2406501 SOD2 0.286869356
ILMN_1792922 SOD2 0.269849418

BAB-A shows an interesting periodic expression pattern when treated with DHT, which would be expected based on the mechanism I described earlier. There's also a slow overall reduction over time.



BAB-B also oscillates, but with a longer and uneven period:



BAB-C drops precipitously at the start and has no clear oscillation pattern (but perhaps a pattern would be apparent with more frequent measurements?):



The non-balding DPCs also fluctuate. For example, here's BAN-A:



The steep drop-off in SOD2 in each case happens within 15-30 minutes, which suggests that AR is acting through a non-genomic pathway, I suppose? So maybe the pathway shown here which acts through the Akt/mTOR/FoxO axis:



Another things is that AR binding to beta-catenin might also inhibit FoxO-mediated transcription, since FoxO uses beta-catenin as a co-activator when cells are under stress.

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