Pax1/Foxa2- 1 of the primary genetic reasons why we balding men- are balding

[barfacan]

IT's just spambots talking to one another.

Nothing to see here

[eldarlmario]

Bro you killed this thread. I didn't understand anything you wrote. I only read the first post

This thread is non-nonsensical research vomit.

IT's just spambots talking to one another.

Nothing to see here

its ok, this thread is only for keen and sincere individuals who wants to help themselves with their own hairloss(their own- not other's)- and the fact that these group of individuals who r in here n not complaining that it's complicated proves the fact that:

1)they've learn something new AND/OR
2)they make the effort to go do some further research themselves on the information being stated here by using simple search engines like 'google search'- and reach a conclusion for themselves whether the said information here are accurate/plausible or not.

Thus- these are the people not complaining that the truckload of information is complicated and hence- the reason why i started this thread in the cutting edge/future treatment section instead of the common 'hair loss treatment' section that are full of the same old stuff like minoxidil, dutasteride, finasteride, spiro, ketoconazole(if you've read my posts on keto- u would see that it's more harmful than it is beneficial to the hair with the reasons stated why backed up by studies and links), etc, etc.

Conclusion- this thread is not for the laymen- especially LAZY 1s

[eldarlmario]

Back to the Cotsarelis patent for promoting hair growth:

Example 5 In Situ and Immuno-Histological Characterization of Novel HF Genes
In situ hybridization and immuno-histochemistry was next used to determine tissue patterns of expression of significantly enriched transcripts in the haired scalp, using human haired scalp samples from different patients than those used to generate the array and flow cytometry data.

Microarray showed that LRRC15 was upregulated 4.5 fold in the haired samples (FIG. 5B). LRRC15 is a transmembrane glycoprotein with leucine-rich repeats. To determine whether LRRC15 functions in cell migration, LRRC15 expression was measured in scalp samples by immuno-histochemistry. LRRC15 was present in Huxley's layer and the cuticle layer of the inner root sheath, especially at the lower follicle (FIG. 6A), which is an area of rapid cell movement during hair growth. Thus, LRRC15 functions in cell migration necessary for hair growth.

Serpin A was up-regulated 5.7 fold in the haired samples. Serpin A is, in another embodiment, a Glade A anti-protease in the same family as anti-trypsin and anti-chymotrypsin. Serpin A was expressed in the companion layer of the outer root sheath, as shown by immuno-histochemistry (FIG. 6B).

GPR49 (LGF5, HG38), another leucine rich repeat-containing protein, was upregulated 6.8 fold in the haired samples, and was expressed in human outer root sheath cells, as shown by immuno-histochemistry. (FIG. 6C). GPR49 is known to be upregulated in the mouse bulge (outer root sheath), thus further confirming results of the present invention. Enrichment of this G-protein in anagen/terminal follicles show its utility as a drug target for stimulating hair growth. <==GPR49 forms a complex with LPR6(which DKK1 inhibits). DKK1 is inhibited by WAY262611, Magnesium L-threonate, Magnesium L ascorbyl 2 phosphate and Valproic acid.

The Angiopoietin-like gene CDT6 (upregulated 18 fold in the haired samples) is an anti-vascular factor that is also expressed in the cornea (Corneal Derived Transcript 6), and thought to maintain the avascularity of the cornea. CDT6 was expressed in the outer root sheath, as shown by immuno-histochemistry (FIG. 6D), which is also avascular.<==Calcipotriol/Calcitriol

GPRC5D (upregulated 19.5 fold in haired samples) is a homologue of RAIG-1 (retinoic acid inducible gene-1). GPRC5D was expressed in the inner root sheath and precortical cells of the hair, as shown by immuno-histochemistry (FIG. 6E).<===Ultra low dose Tretinoin(0.0005%-0.005%)

FGF18 (upregulated almost 6 fold in the haired samples; FIG. 5B) was found to be expressed in the inner root sheath, the companion layer, and to a lesser extent in the suprabasal outer root sheath of the bulge area (FIG. 6F-G).
<== <regulated by FOXP1- and FOXP1 is increased by Valproic acid and ultra low dose Tretinoin
The genes identified in this Example are all enriched in haired scalp, and are thus therapeutic targets for stimulating hair growth.

[bornthisway]

I know at least one person posted about using wounding and calcitriol and said it helped. It's likely worth a try and will probably take an extended time to notice any benefit like all treatments. Probably ideal when used in conjunction with minoxidil between rolling periods. The lowest dose for Tretinoin cream on a popular online pharmacy I've found is 0.025%. Is this concentration too high to get the intended outcome? Was the delivery topical for each of these substances that affected those genes? I wonder what the ideal application / frequency would be. When Follica disrupts the epidermis are they only applying calcitriol at that time?


1,25-dihydroxyvitamin D3: a novel agent for enhancing wound healing.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), has diverse effects in a variety of tissues and cell types, including skin. Since 1,25(OH)2D3 affects both fibroblast and keratinocytes, we evaluated the effect of 1,25(OH)2D3 on wound healing. We investigated the effect of the topically applied 1,25(OH)2D3 or vehicle on the healing of cutaneous wounds in rats in a blinded manner. Wound areas were measured by planimetry technique. Healing was expressed as the percentage of the original wound area that was healed. 1,25(OH)2D3 at concentrations between 5 and 50 ng/day caused a dose-dependent acceleration of healing. Time course and specificity studies indicated that 1,25(OH)2D3 specifically promoted healing between 1-5 days after wounding as compared with vitamin D (0.5 microgram/day), which showed no significant improvement over control. Our results suggest that 1,25(OH)2D3 and its analogues may be a new class of compounds that could be developed to enhance wound healing.

http://www.ncbi.nlm.nih.gov/pubmed/8530536

[eldarlmario]

I know at least one person posted about using wounding and calcitriol and said it helped. It's likely worth a try and will probably take an extended time to notice any benefit like all treatments. Probably ideal when used in conjunction with minoxidil between rolling periods. The lowest dose for Tretinoin cream on a popular online pharmacy I've found is 0.025%. Is this concentration too high to get the intended outcome? Was the delivery topical for each of these substances that affected those genes? I wonder what the ideal application / frequency would be. When Follica disrupts the epidermis are they only applying calcitriol at that time?


1,25-dihydroxyvitamin D3: a novel agent for enhancing wound healing.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), has diverse effects in a variety of tissues and cell types, including skin. Since 1,25(OH)2D3 affects both fibroblast and keratinocytes, we evaluated the effect of 1,25(OH)2D3 on wound healing. We investigated the effect of the topically applied 1,25(OH)2D3 or vehicle on the healing of cutaneous wounds in rats in a blinded manner. Wound areas were measured by planimetry technique. Healing was expressed as the percentage of the original wound area that was healed. 1,25(OH)2D3 at concentrations between 5 and 50 ng/day caused a dose-dependent acceleration of healing. Time course and specificity studies indicated that 1,25(OH)2D3 specifically promoted healing between 1-5 days after wounding as compared with vitamin D (0.5 microgram/day), which showed no significant improvement over control. Our results suggest that 1,25(OH)2D3 and its analogues may be a new class of compounds that could be developed to enhance wound healing.

http://www.ncbi.nlm.nih.gov/pubmed/8530536

for Tretinoin<== it's 0.0005% - 0.005% maximum. i have posted the study that stated:

tretinoin increases GPRC5D by using stem cells as fuel. in low doses(2macromolar) it induces hair follicle differentiation at a stabilized rate. With increasing doses, it depletes stem cells rapidly and stops growth once the stem cells run out. High doeses is also toxic to the hair follicles. and 0.025% is way too high for that. Hence 1mcg/ml is what is needed to be considered as minimally low dose. even with some generous adjustments- 25mcg(study used 600nanograms: rounded off to 1mcg for convenience with adjustments to 5mcg for topical applications) is all that is needed at the most to constitute as low dose. no way generic 0.025% tretinoin is gonna be safe for that by the study and also- by my own experience. So 0.0025%-0.0005% would be the ideal range.

So 5mcg/ml = 0.0005% to 25mcg/ml = 0.0025% would be the ideal range

cumming from a user of tretinoin for 8years(on my face and once- experimentally on the scalp)

IMO, topical calpotriol and topical tretinoin in term of experimentally treating AGA should be used in ultra low doses.

[eldarlmario]

ok i still have not found a small molecule upregulator of:

1)LY6G6D<===3rd most upregulated gene in haired-scalp when compared to bald scalp.

and small molecule downregulator of(Spiro indirectly downregualtes CORIN via antagonsiing Aldosterone- but not1 every's gonna include oral Spiro as part of their regime, including myself)

2)CORIN <==most downregulated gene(even lower than PTGDS- the enzyme for making PGD2) in haired-scalp when compared to bald scalp. Cleaves Brain Natriuetic Peptide(BNP) into 4-32 BNP(non-beneficial for the hair) from 1-32BNP(pro-hair growth BNP)

Mind boogling- because i still do not know what it does to the hair on the balding scalp:

H6 family homeobox 2(i cant make out what the following does in regards to hair on the balding scalp yet(even though it has something to do with inner ear functions)
FOXA(3 forms of FOX genes with FOXA2 being the gene associated with the balding haplotype locus itself) i do not know what to make out of this yet.

perhaps folks here might wanna help out. Doing so, we would have found all the small molecule solutions(at least on paper) in regards to:

1)All the genes mentioned in the Scoliosis study affected by by some of the variants in the AGA/IS Pax1/Foxa2 haplotype
2)Top 5 genes upregulated in haired-scalp
3)Top 5 genes downregulated in bald-scalp.

[eldarlmario]

ok:

Valproic acid, Calicipotriol and Tretinoin tri-axis:

Valproic acid => CD34(UP) but CD200(DOWN)
Calcipotriol => CD200(UP) but CD49F(DOWN)
Tretinoin=> CD49F(UP) but CD34(DOWN)

some sort of balance here.

[eldarlmario]

From Dr Cotasarelis findings:

activator => CD34 positive progenitor stem cells
inhibitor => CD200 high(downregulation of immunoactivity)
resultant=>CD49F high Extra cellular Matrix

=> hair growth

[walrus]

Conclusion- this thread is not for the laymen- especially LAZY 1s

All you have demonstrated in this thread is an ability to type 'hair loss' into Google Scholar and use the copy and paste function of your computer. There is no new insight being offered. Tell me, what are your qualifications that make you not a layman yourself?

[eldarlmario]

"There is no new insight being offered."

Seriously- then why r u even here in this thread in the first place?