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Cnn - Cotsarelis And Christiano Interview 10/18

Discussion in 'New Research, Studies, and Technologies' started by Breyfogle, Oct 18, 2016.

  1. NewUser

    NewUser Experienced Member

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    So now we learn that human biology is tainted with ageism and sexism at What's the Matter U.

    Scientist says 50-50 chance jakinibs could work for pattern baldness.
     
  2. InBeforeTheCure

    InBeforeTheCure Established Member My Regimen

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    @Swoop

    Walker's explanation on this is confusing, at least to me. The bulge is actually deeper than the superficial plexus, but maybe in telogen and/or miniaturized follicles it's not?

    [​IMG]

    But in any case, psoriasis is the better test for this idea than vitiligo, since melanocytes are right up against the dermis.

    [​IMG]
    So for psoriasis, the paper you linked does show dramatically reduced phospho-Stat1 staining in the epidermis after one day, even in areas quite distant from where the capillaries are.

    [​IMG]

    From this, there doesn't seem to be a precedent for believing tofa wouldn't be delivered to the bulge, but of course there could be something we haven't considered that they found in those "pre-clinical models".

    It seems to be at least nearly hopeless. I would have actually expected JAK inhibitors to at least keep follicles in anagen for longer given IFN-gamma is a potent inducer of catagen (Ito et al., 2005) (this of course is relevant to alopecia areata), but so far we've seen no indication that it does even that in A.G.A.

    I've seen worse. :D
     
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  3. Swoop

    Swoop Senior Member My Regimen

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    @InBeforeTheCure

    Interesting. Check here at 1:40, Cotsarelis talks about it;



    [​IMG]

    You can see it on the right, poor hair follicles :(....

    Anyway the bulb does move up obviously and I assume the bulge would be very close to it. In any case the bulb doesn't move further to the top than where the sebaceous gland is located.

    It might even indeed be that the bulge isn't higher than the superficial plexus.... Remember though we also have hair follicles that are "half miniaturized", hair follicles that are in the process of miniaturizing. In these hair follicles I assume the superficial plexus would actually be above the bulge.... However I'm not sure of this.

    More importantly, you can also see the epidermis (epi) on the right and we got the data on tofacitinib. Contrary to what Neal Walker thinks tofacitinib does migrate up to the epidermis, and the epidermis is literally not connected to the blood supply. It even displays it's biological activity pretty damn well and strongly in the epidermis. So it's pretty much impossible the drug wouldn't migrate up to the bulge since it's lower than the epidermis. And the area around the bulge would be actually somewhat vascularized contrary to the epidermis. This would only make it easier for the drug to get into the area around the bulge in comparison to the epidermis.

    Taken all this, their topical endeavor is hopeless. The pills do the same job.

    Well exactly. I guess the mice have fooled us again LOL.

    That's the thing, I don't expect any sort of hair follicle cycle alteration. At least not something that is cosmetically detectable. Pretty damn sure of that. I expect it to work pretty great against the itchy scalp some people have with Androgenetic Alopecia though :p.
     
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    #123 Swoop, Oct 23, 2016
    Last edited: Oct 23, 2016
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  4. Beowulf

    Beowulf Established Member My Regimen

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    Not that I want to get Grasshüpfer pulled into anything, but doesn't that mean that in combination with finasteride or whatever it could actually be pretty handy?
     
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  5. coolio

    coolio Established Member My Regimen

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    "Even transgender regimes stop hairloss 95% of the time, but rarely cause massive regrowth.

    Stopping the cell death in hair follicles is a completely different mechanism to inducing cell proliferation (I think)."



    All that is true. But transplanting the follicle onto an immune-suppressed lab mouse makes it grow back to full size.

    We just don't understand Androgenetic Alopecia well enough.

    .
     
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  6. Beowulf

    Beowulf Established Member My Regimen

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    You mean a dead follicle from a balding scalp? Doesn't that prove that there certainly is some weird immuno-inflamation black magic going on?

    Do you think we just need a thread which is basically just a massive list of everything we know so far about Androgenetic Alopecia without any explanation?
     
  7. KO1

    KO1 Established Member

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    Yep vellus follicles into SCID mice have grown back.
     
  8. Takeela370

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    JAK-STAT Signaling Jump Starts the Hair Cycle. Nov 2016 Volume 136


    Someone posted the link to this on Hairlosscure2020.

    http://www.jidonline.org/article/S0022-202X(16)32374-0/fulltext

    I personally liked,

    "To probe the function of STAT5 in an ex vivo context, the authors isolated skin-derived progenitors from these mice and ablated STAT5 in culture. Loss of STAT5 led to downregulation of genes known to be involved in the induction of anagen such as Wnt6, FGF7, and FGF10 and upregulation of Wnt inhibitors such as Dkk3 and Dlk1. This suggests that STAT5 activation is upstream of the production of these factors, providing a potential link between the JAK-STAT pathway and known modulators of hair follicle cycling. However, it appears that STAT5 phosphorylation is not sufficient to drive production of these anagen-inducing factors in vivo, because activated STAT5 is induced in late catagen, remaining phosphorylated throughout telogen, and Wnt6, FGF7, and FGF10 become upregulated weeks later, in early anagen. This suggests that there may be additional molecular events between STAT5 phosphorylation and the subsequent activation of these anagen-promoting factors. It appears that the interplay of signals within and between several pathways in HFSC compartments may determine whether hair follicles remain quiescent, or if stem cell activation is induced."


    So maybe this is one step, or at the least for now will work synergistically with other treatments.

    And also,

    "Lastly, to perform pharmacologic inhibition of JAK-STAT signaling, Legrand et al. (2016) found that a 10-day administration of systemic ruxolitinib (a JAK1/2 inhibitor that leads to loss of STAT3 phosphorylation in the epidermis) had no effect on the hair cycle of 7-week-old C57BL/6 mice, and it did not affect the phosphorylation state of STAT5 in the DP. In our recent study (Harel et al., 2015), we found that in wild-type mice, topical application (rather than systemic treatment) with JAK inhibitors was required to trigger the telogen-to-anagen transition, possibly due to a requirement for highthreshold local concentrations of the drug in the hair follicle. Further, we found that the timing of topical treatment was crucial: treatment induced hair growth only if administered after 8.5 weeks, during late telogen. This is consistent with the concept of telogen as a progression from a refractory (before 8 weeks) to a competent state (after 8 weeks) for anagen initiation, as elegantly described by the Chuong lab (Geyfman et al., 2015). In our mouse studies, we similarly did not observe an effect of topical JAK inhibitors on STAT5 phosphorylation in the DP. However, we have also shown phosphorylated STAT3 and STAT5 to be active in the HFSCs and outer root sheath during telogen, and phosphorylated STAT3 is also seen sparsely in the DP during early telogen (Harel et al., 2015), suggesting that topical JAK inhibition may be stimulating anagen via pathways that are distinct from those described in this study"


    Soooo many pathways can be affected by these drugs and soooo many pathways that we have not discovered. It is impossible to know 100% what will happen before an experiment is performed. Again, we can predict (realistically just guessing, shot in the dark really) what the outcome of an experiment will be based on known data, but NO ONE can predict with 100% certainty an outcome of an unperformed scientific experiment. Not saying I think this will work, but all we can really do is wait and see. I personally hope it will, at the least, have synergy with other treatments. :D
     
    #128 Takeela370, Oct 24, 2016
    Last edited: Oct 24, 2016
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  9. hairblues

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    NO ONE will be disappointed if this winds up working. I think everyone would gladly eat there words if this worked more efficiently than what is available today.

    people just have different opinions.
     
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  10. FoucaultII

    FoucaultII Established Member My Regimen

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    What?
    Did you just use wikipedia?
    PATHETIC!
     
  11. Swoop

    Swoop Senior Member My Regimen

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    No. It will probably only help with some inflammatory factors in the scalp. It will also probably help against the itch some people have. It will not cause any cosmetically viable regrowth however. That means that it simply will never proceed to being a commercial treatment. Like I said this endeavor is more of a joke than anything.

    You keep hammering on this because that's the only thing you can really say. Look I don't know either if a mix of sh*t from a Hippopotamus coupled with piss from a platypus will work or not with 100% certainty. After all to provide the evidence you would have to do an experiment. But it is deluded to think so.

    So be a man and just admit you are the average example of a hair loss sufferer; very desperate and gullible. I have seen you on hairsite, you are a pretty old member aren't you? God time flies fast, huh?
     
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    #131 Swoop, Oct 25, 2016
    Last edited: Oct 25, 2016
  12. Swoop

    Swoop Senior Member My Regimen

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    Look carefully troll, It cites to a study;

    "Stücker, M; Struk, A; Altmeyer, P; Herde, M; Baumgärtl, H; Lübbers, DW (2002). "The cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis". The Journal of Physiology. 538 (3): 985–994. doi:10.1113/jphysiol.2001.013067. PMC 2290093[​IMG]. PMID 11826181."

    You know what is pathetic? That I refuted the statement from Neal Walker here (CEO Aclaris) and showed why A.M Christiano performed bad science here.

    And that's a FACT.

    But hey let's keep continue with looking at these mice observations LOL.

    [​IMG]

     
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    #132 Swoop, Oct 25, 2016
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  13. hidden

    hidden Member

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    So concerning the new article on jak, gd or bad news ? Sorry but i dont have a scientific backround and did understand 10% of what they are saying ....
     
  14. NewUser

    NewUser Experienced Member

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    Is it a fact in your own mind because you use bolded caps?


    Apparently Tsuji's mouse is demanding a transfer to Christiano's lab. Lol!
     
    #134 NewUser, Oct 25, 2016
    Last edited: Oct 25, 2016
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  15. Stupidon

    Stupidon Established Member

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    Moron.[/QUOTE]
    Please just don't post anymore if you can't make the huge difference between these two models.
     
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  16. FoucaultII

    FoucaultII Established Member My Regimen

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    @Swoop, is oxygen all a tissue needs? Like really?
    Co' mon.

    Oh, Gosh, Michael is such a sexy bald hunk. I've just wetted my pants!
     
  17. Swoop

    Swoop Senior Member My Regimen

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    @Stupidon,

    Exactly he doesn't even understand the difference between the models and the fact that Tsuji his experiment is actually heavily supported on humans. Best is just too stop responding to such people.

    @macaronaroni, made a great comment about that. I like this one too;

    upload_2016-10-25_15-13-27.jpeg
     
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  18. Grasshüpfer

    Grasshüpfer Experienced Member My Regimen

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    Before we put this thread finally to rip...

    Someone mentioned that study once within the context of a completely invalid argument. Of course he got destroyed by swooplol. However my question: Is the study actually good science? I can t believe that nobody ever tried to reproduce something similar.

    This is close: Transplanting aged (mice) follicles onto young mice rejuvenates them.
    https://www.ncbi.nlm.nih.gov/pubmed/26940664

    I know about the study that shows that balding hair continues miniaturization transplanted to the body. But thats no surprise - so does beard hair or pubic hair, because it adjusts to the environment.
     
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  19. Swoop

    Swoop Senior Member My Regimen

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    Indeed! He could give that mice a full coat. Not only that though. These are actually human cells growing in that mice. He simply took human cells and used the mice as a host to let the human hair follicle develop including all structures like sebaceous gland and APM. That's so damn different than using a mice itself as a drug model for Androgenetic Alopecia.

    A mice as a drug model for Androgenetic Alopecia has led to NOTHING after decades. After all we have discovered zero potent hair growth agents through research in the last 60+ years pretty much. Both most potent growth agents we have (minoxidil and PGF2a analogues), we have discovered through accident in vivo on humans. Just think of how f*cking funny that is, well actually it's sad.

    Also it's simple. If you take (stem)cells and you implant them in humans a full hair follicle can develop as already has been proven. This gives great support to Tsuji his science. Jahoda has shown that by implanting dermal sheath cells on his wife his fore-arm, and the splitting of hair follicles shows that through studies. The hair follicle (stem)cells are capable of regenerating a full hair follicle.

    And lastly @NewUser, I hate to tell it to you but Tsuji is ahead of the curve than A.M Christiano et al. in terms of the culturing problem of these cells. You make yourself stupid again and I wonder why you constantly refer to Tsuji anyway.
     
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    #139 Swoop, Oct 25, 2016
    Last edited: Oct 25, 2016
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  20. coolio

    coolio Established Member My Regimen

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    Exactly. Using a mouse as a life-support system for a chunk of human skin is one thing. Testing drugs on the mouse's own hair is something else. The latter method is pretty much useless.
     
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