inmyhead
Senior Member
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Maybe he got depression from finasteride or something? His personality completely changed, lol.
South Korean Scientists Has Developed A New Type Of Biochemical Material To Prevent Hair Loss
- Thread starter Xaser94
- Start date
Maybe he got depression from finasteride or something? His personality completely changed, lol.
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Got the supplemental info (attached). Look at the "hair follicle" from balding scalp - an empty husk of despair.
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Clinical evidence and characterization of everyone on this forum in a single post. One-two punch, Boom!
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And...?
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https://www.ncbi.nlm.nih.gov/pubmed/26868914
Emotional Consequences of Finasteride: Fool's Gold. It's very possible.
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And what?
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Oh dear god it's still there bombarded with that protein. Seriously I think it's a remarkable discovery.
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at least they found something ; p That must be a person who is bald for quite a long time. I guess If we keep taking some kind of treatment the "activity" in there must be slightly better eventhoughdon't know much about that
I mailed this morning and received:
"
Thank for interest to the hair study.
Currently, we are testing toxcicity of the reagent strongly, and later we will progress to the pre-clinical studies.
Best
Kang-Yell"
I think they are trying to keep something hidden.
Guys we can't know if this material work on humans. So, We must contact as every pharmacy as can and say them to work on CXXC5 inhibitors. What about this?
"
Thank for interest to the hair study.
Currently, we are testing toxcicity of the reagent strongly, and later we will progress to the pre-clinical studies.
Best
Kang-Yell"
I think they are trying to keep something hidden.
Guys we can't know if this material work on humans. So, We must contact as every pharmacy as can and say them to work on CXXC5 inhibitors. What about this?
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Formality may be appreciated as well.
@Admin what is the protocol to reaching out for an interview or emailing questions?
There is no CXXC5 inhibitor at the market, or I couldn't find. Therefore, We should encouarge pharmacy companies to product CXXC5 inhibitors by contacting them. If the drug PTD-DBM doesn't work on human, then "The cure" probably will be available in 30 years.
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Does anyone think there is a correlation between prostaglandins and this new discovery? we know DHT > elevated PGD2 (inflammation) > hair loss... Maybe the elevated PGD2 and the inflamation that comes with it is preventing the WNT pathway from functioning properly? There must be some sort of missing link in this chain reaction.
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As far as I’m aware we don’t know what the chemical compound PTD-DBM is, and until it’s given a CAS designation no lab in China is gonna be able to manufacture it...
Sanchez1234
Experienced Member
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You can ask LUO from 2hpharm if he can help out? He manufactures high quality compounds. He supplied setipiprant + darolutamide and it tested legit and more affordabke then Kane.
He is very helpfull and speaks good english.
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Inflammation doesn't seem to play much causative role in A.G.A if at all, but Wnt signaling clearly does (as suggested by many Wnt-related genes affecting A.G.A risk, and the absence of inflammation-related genes affecting A.G.A risk). And genetic variants affecting hair follicles' response to PGD2 also have no effect on A.G.A risk, so that's probably not a good candidate either. Also, while we can infer that inhibition of Wnt signaling is a major causative factor in A.G.A risk, we don't know whether differential regulation of CXXC5 in particular is a cause or a downstream redundant effect.
Having said that, what can we say about regulation of CXXC5 in hair follicles?
In the dermal papilla in vivo, Cxxc5 mRNA is highest in cells where Wnt signaling activity is the highest (Yang et al., 2017). This is consistent with previous reports that Cxxc5 is a negative feedback regulator of Wnt signaling.
From top to bottom, the DP clusters are Cluster 1 (C1), Cluster 3 (C3), Cluster 2 (C2), and Cluster 4 (C4). Expression of Lef1, a Wnt target gene, is a good marker for Wnt pathway activity. Lef1 expression is highest in Cluster 2, as are Wnt target genes Fgf7, Fgf10, and Alx4. Cxxc5 mRNA expression is also highest in Cluster 2.
CLUSTER 2 includes...
Genes, Fold change, FDR
Lef1, 2.42, 6.72E-08
Cxxc5, 2.17, 2.54E-03
But this latest study found that Cxxc5 protein is negatively correlated with Wnt signaling activity. And in the human hair follicle to the left, Cxxc5 protein was most highly expressed near the bottom (i.e. Cluster 4) DPCs, where Wnt pathway activity is weakest.
But in their in vitro experiment, they found that treatment of DPCs with Wnt3a strongly induced Cxxc5 protein expression - this seemingly contradicts in vivo data showing an inverse correlation. It does, however, agree with in vivo single-cell transcriptome data showing a positive correlation between Wnt signaling activity and Cxxc5 mRNA.
And here again, another in vivo observation where they used valproic acid, which as expected stabilized beta-catenin but did not induce Cxxc5 protein expression.
Here's a figure from the supplemental info showing expression of beta-catenin and Cxxc5 protein through the hair cycle:
Neither beta-catenin or Cxxc5 are expressed in telogen. Beta-catenin protein accumulation comes first, but Cxxc5 protein is still low. Later, Cxxc5 is strongly expressed and beta-catenin starts to fade. Catagen soon follows, beta-catenin fades further, and Cxxc5 eventually fades as well. By the next telogen, both beta-catenin and Cxxc5 are gone once again.
So...
In vitro: Wnt -> beta-catenin stabilization -> Cxxc5 mRNA -> Cxxc5 protein -| Wnt pathway activity (negative feedback)
In vivo, anagen: Wnt -> beta-catenin stabilization -> Cxxc5 mRNA -?- no Cxxc5 protein (permissive for long-lasting, amplified Wnt signaling)
In vivo, catagen: Cxxc5 protein is expressed at high levels and inhibits the Wnt pathway
What could explain this? Maybe there's some secreted factor that's present in vivo, but not in vitro, that disrupts Cxxc5 protein stability? There's actually an analogous system that also works on the Wnt pathway, which very briefly goes like this:
Wnt -> Fzd, Lrp5/6 -> beta-catenin -> Znrf3, Rnf43 -| Fzd
Znrf3 and Rnf43 are transmembrane E3 ubiquitin ligases that promote the endocytosis and proteasomal degradation of Frizzled (the Wnt receptor). Znrf3 and Rnf43 are both themselves Wnt target genes (much like Cxxc5), and therefore act as negative feedback regulators of Wnt signaling (also like Cxxc5). There's a family of secreted growth factors called R-spondins (RSPO for short). R-spondin forms a complex with its receptor Lgr4 or Lgr5 and with Znrf3/Rnf43, and when this happens, it's the Rspo/Lgr/Znrf43 or Rnf43 complex that undergoes proteasomal degradation. As a result, Wnt signaling persists much longer, and is much stronger.
So I'm wondering if there's a secreted protein analogous to R-spondin -- sort of like an endogenous PTD-DBM -- that inhibits Cxxc5 protein stability. This protein, if it exists, would have to be expressed in anagen, fall in late anagen prior to onset of catagen, and might also be downregulated in A.G.A hair follicles. Any ideas? If anyone knows of such a protein, or another possible mechanism that might regulate Cxxc5 protein stability, then we can discuss how that mechanism itself is regulated.
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You're so much way ahead from nearly everybody here that you need to talk directly to those South Korean researchers to get this answer, you should definetly do it.
Good post
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BTW you missing the SFRP1 that also downregulates WNT\b,
also as from latest Hair Congress during Androgenetic Alopecia you have excessive DP cells migration - https://www.hairlosstalk.com/intera...omote-vellus-to-terminal-reconversion.109789/
>> This protein, if it exists, would have to be expressed in anagen, fall in late anagen prior to onset of catagen, and might also be downregulated in A.G.A hair follicles. Any ideas?
It could be FGF9 - protein response for PGE2 receptors activation.
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@InBeforeTheCure Agreed, you are way ahead of most if not all of us on this topic. You clearly know your stuff, thanks for the post. I'm currently researching the WNT pathway and CXX5 but lack a complete understanding at the moment. However, I have to disagree with you about the relationship between inflammation and Androgenetic Alopecia. if Inflammation wasn't related to Androgenetic Alopecia then we wouldn't be seeing some users having success with CRTH2 inhibitors, and the almighty mysterious (and controversial) Brotzu lotion wouldn't be effective. In my research I have found numerous studies relating the WNT pathway to prostaglandins - specifically PGE2. I have attached a document of some particularly interesting articles on that topic. I encourage you to look at the first article specifically. That one discusses the relation of PGE2 and WNT, and was published before the famous Cotsarellis study. Again thanks for your research and hopefully you can use your expertise in this topic to further our understanding