Updated Research and Knowledge - Cutting Edge

[Forestry]

rice bran

I've only ready the first link SriHanuman , that is a good read and shows RB-SCE a decent alternative to minoxidil.

In terms of the stack, Linoleic Acid (LA) is there (here I'm lumping together GLA and LA) with Evening Primrose*.

The new item appears to be Gamma Oryzanol (OZ).

I wish the study went out past 4 weeks. The OZ really kicked in at week 4.

*per Wikipedia, natural sources of LA:
Name % LA
...
Safflower oil 74.62%
Evening Primrose oil 73%
...
Grape seed oil 69.6%
Sunflower oil 65.7%
...
Walnut oil 51%
Sesame oil 45%
Rice bran oil 39%

[TubZy]

SO....you're paying 124$ / week for TB500 ???????

Ballin lol. Yeah I just want to see if it works well or not. Not really planning to stay on it long term unless I get pretty decent results, just need some thickening, hairline is still pretty decent (NW1).

Higher dose topical OC has seemed to cut my shedding down a lot.

I do it SubQ or IM. I think you should you at least 8mg or even 10mg if you could afford it. I have clopro coming in soon so that should be a decent growth stim combo (clopro & TB500).

[SriHanuman]

rice bran:

http://www.ncbi.nlm.nih.gov/pubmed/24389480

http://www.ncbi.nlm.nih.gov/pubmed/26632177 full article: https://www.jstage.jst.go.jp/article...b15-00387/_pdf

[Seuxin]

WNT agonist is very important.

TheKaneShop is selling a WNT agonist named "6BIo", as 99$ for 500mg. Nevertheless i don't know the amount to use per day. I think it's a little amount because WNT agonist at high dose can be dangerous.

It can be a good addition...

In addition, Follistatin is VERY IMPORTANT for hair, it's used in the famous Histogen ( HSC) protocol ( KGF, VEGF, and Follistatin), nevertheless AFAIK, there is different type of follistatin....Maybe it could be good to find a simple an cheap way to increase production of follistatin.

-> Increasing VEGF is simple ( With hypoxia like Stemoxydine, or with Minoxidil )
-> Increasing KGF is simple ( With Minoxidil, or buying directky KGF for cheap on the skinactive website )

So we need to find a way to increase Follistatin !

And we have to find the amount to use for 6-BIO.

[Forestry]

a related study

Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial.
...
These results demonstrate that a single intradermal administration of HSC improved hair growth in subjects with androgenetic alopecia and is a clinical substantiation of previous preclinical research with Wnts, follistatin, and other growth factors associated with wound healing and regeneration.

[Forestry]

regenerating hair follicles

i have been following (this forum is great, special thanks to Chemical for elaborating your findings) and researching and wanted to add this.

when reading wikipedia on keratinocyte differentiation and the associated expression of specific keratins at each stage, i came to the section on the Role in Wound Healing, and the associated reference:

...Wounds to the skin will be repaired in part by the migration of keratinocytes to fill in the gap created by the wound. The first set of keratinocytes to participate in that repair come from the bulge region of the hair follicle and will only survive transiently... At the opposite, epidermal keratinocytes, can contribute to de novo hair follicle formation during the healing of large wounds.

https://www.ncbi.nlm.nih.gov/pubmed/17507982

"the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles."

I wonder if this (WnT signalling) study has been conducted in the presence of DHT and receptor diminishing regimen for such.

[Seuxin]

I actually have been using tb500 for the past few weeks on and off. I have taken a few weeks off and now back on 8mg injected one a week. I bought enough this time to run it for at least 6 weeks at 8mg a week. It definitely has an impact on hair color and growth because my hair did look way healthier and darker when I only used it for a 3 weeks in the past . The only downside is the price as it's costing me $31 for 2mg vial but the stuff I have it 100% legit. I heal way quicker too from weight lifting. I just did my first shot again this past Wednesday and plan to keep going for another 5 weeks or more if I have the money.

SO....you're paying 124$ / week for TB500 ???????

[champpy]

Hey Tubzy, can you tell us the source you got the TB4 from?

[Unsure1]

Where You scalp or sub q injecting tb 500?
Injecting 2-4mg into the scalp weekly I saw minor quality improvement though nothing too significant

[burtandernie]

Could you take this stuff orally and how much of each thing to get any result? There still is a pretty large number of people looking for that magic fin alternative. I guess I should really try fin before trying all this other random stuff.

[jamesst11]

it's hard to tell what's going on this pics? can you take a couple more with your hair combed the same way and at the same angle?

[lukey]

Chemical, could you please confirm how much OL and EGCG we should be using per ml? Thanks.

[TubZy]

Thoughts? More than thoughts. Thymosin beta 4 is an absolute goldmine. (Thanks for sharing this)

Thymosin beta 4 induces hair growth via stem cell migration and differentiation.

Without looking too hard I found this. TB4 acts directly on the stem cells to induce hair follicle growth. Sadly the abstract doesnt go over the mechanism of TB4 that they discovered.


Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells.

HGF is a known stem cell pluripotency maintainer providing further evidence of TB4's stem cell effects.

Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner.

We know that VEGF expression leads to increased hair follicle size and growth rate.

Regulation of glycogen synthase kinase-3 by thymosin beta-4 is associated with gastric cancer cell migration.

And it also inhibits GSK3β which leads to more β-Catenin. However the study mentioned they noticed a decrease in β-Catenin in response to TB4.

Over-expression of thymosin beta4 promotes abnormal tooth development and stimulation of hair growth



Looking at the deeper mechanisms of TB4 we see that it interacts with laminin 5. I've never heard of laminin 5 so I did some research:

Laminin-10 is crucial for hair morphogenesis



So it seems laminin 5 is crucial for cellular adhesion. But what does cellular adhesion do?

http://www.nature.com/nrm/journal/v4/n9/images/nrm1199-i2.gif

Cellular adhesion is necessary for epithelial mesenchymal transition to take place and it also increases intracellular β-Catenin. You can read more about E-cadherins role in hair growth here:

E-cadherin controls adherens junctions in the epidermis and the renewal of hair follicles

It looks like TB4 is designed for the sole purpose of growing hair, nearly everything it does is directly promotes the development of hair follicles. I will doing more research on ways of increasing TB4 (endogenously or exogenously).

While I was researching laminin 5 I came across this excerpt which talks about DPC regeneration by "growth of papilla cells in 3D spheroid cultures" implanted into skin:



I dont know what to say. Just let that sink in.




You are very welcome.

I started off using minox, emu oil, oleuropein, Saw palmetto and ketoconazole. Now I'm using Minox, EGCG, OL, GLA, ketoconazole and miconazole. I'm going to add Valproic acid, apple polyphenols, Rosemary and a different brand of GLA in the form of safflower oil. I think this is as far as I will go and this should be more than enough to see steady regrowth. The problem is I'm being impatient and thats a bad trait to have when watching hair to grow (or a tree to grow). If I were to choose a few core treatments to stick to I'd say minox, egcg, ol, keto, rosemary and gla. We keep discovering new studies and pathways that enhance or inhibit hair growth so its inevitable that in a few months time this protocol will change. This is still an experiment in progress so nothing is fixed yet until I've become nw0. Moreover, treating AGA is an optimisation problem where we have to find the treatments that have the best cost to effectiveness ratio and ease of acquisition/application - which takes trial and error. And even after complete regrowth, we have to find a maintenance protocol that doesnt require aggressive planning or time. I firmly believe in never settling for less. There is always room for improvement.

Looking at histogens preliminary results and theory I would say their treatment has potential to grow hair in less aggressive AGA. This idea of using cultured stem cell/growth factors (?) injected only once into scalps is definitely more convenient than daily topical use. The only problem is AR.

Replicels methodology is better that histogens on paper:

https://youtu.be/cCe5mg7X6zg?t=122

I previously stated that these implanted DPC cells might fail to create a functional hair canal with outer root sheath cells but that was ignorant of me to say without fully understand how follicular neogenesis works.



Instead of occipital hair cells I think replicel might have more success with beard DPC since they actually thrive in the presence of DHT and release IGF-1 to nearby follicles. I realise that culturing these cells is not an easy task so atm its all looking really good on paper. But just because it seems to work on paper and mice doesnt mean it'll translate the same in human balding scalp.



For now all we can do guess when they will be ready to release their treatments. I think the main problem is the researchers like hyping their work before they can actually execute it properly. I think we should stop holding our breath for these companies and look for alternative treatments that we can use immediately, and when these do finally come out, it'll be a win-win. Otherwise you'll just be setting yourself up for disappointment.

Yes I'm nearly finished writing up the material for the new thread which will all the treatments with the relevant dosing and science, plus all the research in this thread formatted nicely so it's easy to find. Its proving to harder than I thought gathering all the research scattered all over this thread but I'm nearly done.

I've stated before that I fully believe my results were attributed to minox with the other treatments merely potentiating the rate of regrowth. When I tried minox, fin and keto back in april 2015 it took 2 months before I saw visible improvement and it wasnt anything spectacular. With OL + Minox and keto/mico I saw very fast terminal differentiation of vellus hairs when I was applying 3x a day for 2 weeks. (I will make a proper progress log too). I will talk more about testing methodology and gauging effectiveness of treatments in the new thread so I dont keep repeating myself however the point you raise about which treatment is actually working - is important.

I cant comment on keto and RU since their side effects are subjective and varying but personally I havent experienced anything bad with Keto (I use the cream form). This shedding that people experience could be a good sign of new anagen entry but it could also be coincidence - you will see more bad experiences because people dont post unless they see a change for the worst. Thats something to keep in mind when reading anecdotes.



Targeted disruption of the p160 coactivator interface of androgen receptor (AR) selectively inhibits AR activity in both androgen-dependent and castration-resistant AR-expressing prostate cancer cells.

Good find as always Seuxin.

Nearly forgot:

http://imgur.com/a/g6TdQ

http://imgur.com/a/aV65d - taken today.

I actually have been using tb500 for the past few weeks on and off. I have taken a few weeks off and now back on 8mg injected one a week. I bought enough this time to run it for at least 6 weeks at 8mg a week. It definitely has an impact on hair color and growth because my hair did look way healthier and darker when I only used it for a 3 weeks in the past . The only downside is the price as it's costing me $31 for 2mg vial but the stuff I have it 100% legit. I heal way quicker too from weight lifting. I just did my first shot again this past Wednesday and plan to keep going for another 5 weeks or more if I have the money.

[Seuxin]

The problem with TB500 (Thymosin beta 4) is it needsto be injected, and it's expensive ! In addition, i think some peoples already tried it

[Chemical]

Thoughts on thymosin beta 4?

Thoughts? More than thoughts. Thymosin beta 4 is an absolute goldmine. (Thanks for sharing this)

Thymosin beta 4 induces hair growth via stem cell migration and differentiation.

Without looking too hard I found this. TB4 acts directly on the stem cells to induce hair follicle growth. Sadly the abstract doesnt go over the mechanism of TB4 that they discovered.


Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells.

HGF is a known stem cell pluripotency maintainer providing further evidence of TB4's stem cell effects.

Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner.

We know that VEGF expression leads to increased hair follicle size and growth rate.

Regulation of glycogen synthase kinase-3 by thymosin beta-4 is associated with gastric cancer cell migration.

And it also inhibits GSK3β which leads to more β-Catenin. However the study mentioned they noticed a decrease in β-Catenin in response to TB4.

Over-expression of thymosin beta4 promotes abnormal tooth development and stimulation of hair growth

Accelerated hair growth in thymosin β4 transgenic mice The effect of thymosin β4 on hair growth was analyzed in the transgenic mice. We watched the hair growth pattern of transgenic mice after birth but could not detect any differences in the onset of hair growth when compared with the wild type mice. However, we found significant difference in the speed of hair re-growth after shaving. Shaved mice were observed and the speed of hair re-growth was compared by measuring the hair area on the shaved spot at 2 weeks using an image analysis program. The speed of hair growth on the skin of the transgenic mice was accelerated as shown in Fig. 3. These data suggest that the increased expression of thymosin β4 in the hair follicles (Fig. 1B) promoted hair re-growth in the transgenic mice. To analyze the expression pattern of thymosin β4 on the hair follicle, we stained for thymosin β4 in the skin of transgenic mice. As shown in Fig. 3B, thymosin β4 was expressed on surface of the hair follicles especially in the external root sheath.

Induced expression of laminin-5 in thymosin β4 transgenic mice

We examined the expression of laminin-5 in the thymosin β4 over-expressing mice since laminin-5 was one of the candidate genes associated with hair growth among the proteins upregulated by thymosin β4. Western blot analysis and immunohistochemistry were used with the skin of wild type and transgenic mice to characterize the expression of laminin-5. As shown in Fig. 4A, Western blot shows that the expression of laminin-5 was increased approximately 5-fold in the transgenic mice relative to the wild type mice. Immunohistochemistry showed that the expression of laminin-5 was specifically increased in the root of the hair follicles and this staining pattern is different from that of thymosin β4 (Fig. 4B). The expression of laminin-5 around the root of the hair follicle suggests that laminin-5 is induced by the over-expression of thymosin β4 and that this induced laminin-5 expression may stimulate hair follicle stem cells and play a role in the thymosin β4- stimulated hair growth.

Looking at the deeper mechanisms of TB4 we see that it interacts with laminin 5. I've never heard of laminin 5 so I did some research:

Laminin-10 is crucial for hair morphogenesis

Our results, as well as the results of a number previous studies, suggest that laminin-10 supports hair follicle development through a mechanism other than the maintenance of dermal–epithelial cohesion. A comparison between inhibition of laminin-5 and laminin-10 in the skin illustrates this point. In human skin xenografts, laminin-5 antibodies induced extensive epidermal detachment within 24 h of application, while in our studies, skin treated with laminin-10 antibodies did not show blisters or epidermal detachment even after 3 weeks. Similarly, extensive blistering is seen in patients with HJEB, who lack laminin-5. Absence of laminin-5 in Lama3 –/– mice produced extensive epidermal detachment as well as detachment-associated cell death (anoikis). In contrast, in our studies, we were unable to demonstrate significant epidermal detachment or anoikis in Lama5 –/– mouse skin. On the other hand, while inhibition of laminin-10 in both human and murine skin produced marked effects on hair follicle development, no hair follicle defects were demonstrated in laminin-5/6 null mouse skin, and hair follicle development is typically normal in HJEB patients. In conclusion, laminin-5 and laminin-10 appear to have non-overlapping functions in the skin, with laminin-5 promoting epidermal adhesion and laminin-10 promoting epithelial development.

So it seems laminin 5 is crucial for cellular adhesion. But what does cellular adhesion do?

http://www.nature.com/nrm/journal/v4/n9/images/nrm1199-i2.gif

Cellular adhesion is necessary for epithelial mesenchymal transition to take place and it also increases intracellular β-Catenin. You can read more about E-cadherins role in hair growth here:

E-cadherin controls adherens junctions in the epidermis and the renewal of hair follicles

It looks like TB4 is designed for the sole purpose of growing hair, nearly everything it does is directly promotes the development of hair follicles. I will doing more research on ways of increasing TB4 (endogenously or exogenously).

While I was researching laminin 5 I came across this excerpt which talks about DPC regeneration by "growth of papilla cells in 3D spheroid cultures" implanted into skin:

Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

The observation of hair follicles within grafts, as described above, suggests that the 22% restoration of papilla signature is sufficient for follicle neogenesis. However, as complete hair-follicle morphogenesis involves epithelial:mesenchymal interactions, it is likely that external paracrine signals will be required for full signature restoration and development of external hairs. Importantly, in this study, we have demonstrated that dermal spheroids are, by themselves, capable of initiating the hair induction process in non-hair-bearing human skin, where there are no previous epidermal “hair-follicle” signals.

I dont know what to say. Just let that sink in.

It seems that your regiment has evolved since you began this thread and that it continues to change. Do you think you're near a point where you will have finalized the regiment or do see it being a work in progress indefinitely?

Also, what is your opinion on the current pipeline of treatments? Which do you think will have the greatest chance of success if any? (Replicel, histogen, SM, CB, etc.)

Thanks again. I wish I were half as knowledgable as you on this.

You are very welcome.

I started off using minox, emu oil, oleuropein, Saw palmetto and ketoconazole. Now I'm using Minox, EGCG, OL, GLA, ketoconazole and miconazole. I'm going to add Valproic acid, apple polyphenols, Rosemary and a different brand of GLA in the form of safflower oil. I think this is as far as I will go and this should be more than enough to see steady regrowth. The problem is I'm being impatient and thats a bad trait to have when watching hair to grow (or a tree to grow). If I were to choose a few core treatments to stick to I'd say minox, egcg, ol, keto, rosemary and gla. We keep discovering new studies and pathways that enhance or inhibit hair growth so its inevitable that in a few months time this protocol will change. This is still an experiment in progress so nothing is fixed yet until I've become nw0. Moreover, treating AGA is an optimisation problem where we have to find the treatments that have the best cost to effectiveness ratio and ease of acquisition/application - which takes trial and error. And even after complete regrowth, we have to find a maintenance protocol that doesnt require aggressive planning or time. I firmly believe in never settling for less. There is always room for improvement.

Looking at histogens preliminary results and theory I would say their treatment has potential to grow hair in less aggressive AGA. This idea of using cultured stem cell/growth factors (?) injected only once into scalps is definitely more convenient than daily topical use. The only problem is AR.

Replicels methodology is better that histogens on paper:

https://youtu.be/cCe5mg7X6zg?t=122

I previously stated that these implanted DPC cells might fail to create a functional hair canal with outer root sheath cells but that was ignorant of me to say without fully understand how follicular neogenesis works.

Human DP cells isolated from temporal scalp dermis (Promocell, Heidelberg, Germany) from six donors were propagated in vitro according to manufacturer's recommendations. Alkaline phosphatase activity, a DP marker which correlates with hair-inducing capacity, was measured in vitro using the BCIP/NBT substrate on passage 5 DP cells. Alkaline phosphatase activity was variable between samples, with cells from 3 of the donors showing alkaline phosphatase activity in more than 50% of the cells (Table 1). DECs were constructed by combining DP cells with rat tail collagen type 1, adding NFKs on top and bringing the constructs to the air-liquid interface for 2 days before grafting onto female nude mice. Eight weeks after grafting, HFs were observed in mice grafted with the 3 human DP cells with higher alkaline phosphatase activity (Table 1, Figure 1a). HFs had a bulb, dermal sheath, hair matrix and cortex (Figure 1b). Epithelial compartments of the HFs were intact with concentric layers of inner and outer root sheaths, sebaceous glands and hair shaft (Figure 1c-e).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947143/

Instead of occipital hair cells I think replicel might have more success with beard DPC since they actually thrive in the presence of DHT and release IGF-1 to nearby follicles. I realise that culturing these cells is not an easy task so atm its all looking really good on paper. But just because it seems to work on paper and mice doesnt mean it'll translate the same in human balding scalp.

Also I somewhat agree with you regarding how companies indicate they are only a few years away but do you really think Replicel / Histogen / other treatments aren't going to work or be available soon? (They mentioned in 2018)

Can you make a post on the exact supplements you are taking and dosages? I know one of them was Oleuropein.

I was curious how can you be sure that your mixtures / suggestions are working and it isn't because of the Minoxidil only?

I have read some people have bad experience with keta shampoo / nizoral and experience massive hair falling out. I don't want to risk having clumps of my hairs gone. Also there was a lot of users that got on the RU wagon but later on people experienced side effects with RU too and now CB is suppose to be the miracle...

For now all we can do guess when they will be ready to release their treatments. I think the main problem is the researchers like hyping their work before they can actually execute it properly. I think we should stop holding our breath for these companies and look for alternative treatments that we can use immediately, and when these do finally come out, it'll be a win-win. Otherwise you'll just be setting yourself up for disappointment.

Yes I'm nearly finished writing up the material for the new thread which will all the treatments with the relevant dosing and science, plus all the research in this thread formatted nicely so it's easy to find. Its proving to harder than I thought gathering all the research scattered all over this thread but I'm nearly done.

I've stated before that I fully believe my results were attributed to minox with the other treatments merely potentiating the rate of regrowth. When I tried minox, fin and keto back in april 2015 it took 2 months before I saw visible improvement and it wasnt anything spectacular. With OL + Minox and keto/mico I saw very fast terminal differentiation of vellus hairs when I was applying 3x a day for 2 weeks. (I will make a proper progress log too). I will talk more about testing methodology and gauging effectiveness of treatments in the new thread so I dont keep repeating myself however the point you raise about which treatment is actually working - is important.

I cant comment on keto and RU since their side effects are subjective and varying but personally I havent experienced anything bad with Keto (I use the cream form). This shedding that people experience could be a good sign of new anagen entry but it could also be coincidence - you will see more bad experiences because people dont post unless they see a change for the worst. Thats something to keep in mind when reading anecdotes.

To Seek : Modulation of Androgen Receptor Activity by P160

https://www.google.fr/search?tbm=bks...+by+P160&hl=fr

Targeted disruption of the p160 coactivator interface of androgen receptor (AR) selectively inhibits AR activity in both androgen-dependent and castration-resistant AR-expressing prostate cancer cells.

Good find as always Seuxin.

Nearly forgot:

http://imgur.com/a/g6TdQ

http://imgur.com/a/aV65d - taken today.