Celastrol Enhances Atoh1 Expression in Inner Ear Stem Cells and Promotes Their Differentiation

Discussion in 'Alternative Treatments and Research' started by PolishSoldier87, Oct 11, 2018.

    1. PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150060/

      In summary, here we demonstrated that Celastrol treatment stimulated expression of the master transcription factor Atoh1 in inner ear stem cells and subsequently derived spheres. Moreover, Celastrol facilitated the commitment of inner ear stem cells to neuronal-like cells, which might hold great therapeutic promise for further exploitations.

      https://www.amazon.com/Thunder-God-Vine-Root-20/dp/B0145XJQZ2

      11aaa.jpg
       
      • Genius Genius x 3
    2. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      FANTASTISCH!!!!!
      "Transcription factor Atoh1 is the key player during HC development and regeneration."
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299128/

      I'm blown away I didnt find this already I've spent hours and hours searching for ways to increase atoh1. Now is this something we can take in high enough doses to do anything? It's worth looking into!
       
      • Agree Agree x 1
    3. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      My studies indicate only 1/3 gram is safe oral dose. Seems too low for oral therapeutic effect.
       
      • Like Like x 1
    4. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Pls give me a source.
       
    5. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      • Like Like x 1
    6. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      How many/day do we need? What do you think?
       
      • Good Question Good Question x 1
    7. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      Maybe if we stack all known natural substances that have properties implicated in hair cell regeneration then we can do this, like egcg, thunder god root, carrageenan, etc.

      I wish more people on this forum would realize that this type of thing potentially holds the greatest chance to help us anytime soon. Those of us with certain types of cochlear damage. It may seem far fetched but what if it is not?
       
      • Agree Agree x 2
    8. uae96
      Thinking

      uae96 Member

      Tinnitus Since:
      6/14/2015
      Cause of Tinnitus:
      Noise induced
      I placed an order.
       
      • Like Like x 3
    9. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      What do we have to do to make these cells to become hair cells after differentiation?
       
      • Good Question Good Question x 2
    10. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      Atoh1. I think. I believe differentiation means becoming hair cells.
      I just ordered some deer antler and some thunder god root.
       
      • Like Like x 1
      • Helpful Helpful x 1
    11. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      But I can't find this about hair cells it in this article. It's only about neuronal cells, I think.

      English is not my native language and maybe I am wrong.
       
    12. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      I could be wrong too but I'm under the impression that increasing atoh1 is the primary mechanism behind cochlear hair cell regeneration. My main question is what is up with the scientists that publish these papers? Why don't they ever follow through on this research? If you discovered a mechanism to regenerate hearing wouldn't you follow through? That's Nobel Prize level stuff.
       
      • Agree Agree x 5
    13. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      It's from June 2018 so a new thing.
       
    14. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Don't forget to tell us about the effects :)

      From article:
      The third-generation of utricular maculae-derived sphere cells was stimulated to differentiate with 50 ng/ml NT-3 and 100 ng/ml BDNF (R & D Systems, Minneapolis, MN, USA).

      So maybe its not so stupid to take it with Matrine (NT-3) and Lurong (NT-3, BDNF, IGF-1)
       
      • Friendly Friendly x 2
    15. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Neurog1 can partially substitute in Atoh1 function in hair cell differentiation during organ od Corti development.

      https://www.ncbi.nlm.nih.gov/m/pubmed/26209643/

      Despite the presence of many HCs with stereocilia these mice are deaf.

      Combining Neurog1 in one allele with removal of floxed Atoh1 in a self-terminating conditional mutant (Atoh1-Cre; Atoh1(f/kiNeurog1)) mouse results in significantly more differentiated inner HCs and outer HCs that have a prolonged longevity of 9 months compared with Atoh1 self-terminating littermates.

      Curcumin, which is found in turmeric, functions as a strong anticancer agent in different cancer models through the modulation of DNMT, HAT/HDAC, and miRNAs that target the Nrf2, Neurog-1, RARβ2, PTEN, and P53 pathways
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924975/

      103. Shu L, Khor TO, Lee JH, Boyanapalli SS, Huang Y, Wu TY, et al. Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells. AAPS J. 2011;13:606–14​

      Maybe we shouldn't give up curcumin but add it to our set.
       
      • Informative Informative x 2
    16. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      that's cool. because curcumin blocks atoh1. I really did feel like curcumin was making me better. I really think you are on to something here. wouldn't that just be so awesome if we actually could pull this off?
       
      • Agree Agree x 3
    17. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Curcumin blocks atoh1? Pls tell me more about this and provide source if you may.
       
    18. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      No bullshit.
      I get my curcumin at the hippy grocery store called earthfare and am about to go get it this evening and in the middle of this very conversation I look down at my phone and this email popped up. 20181011_181350.jpg
       
    19. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      "Furthermore, inhibition of histone acetyltransferase (HAT) activity by curcumin partially blocks the DAPT-induced accumulation of Atoh1 mRNA, further indicating a need for ongoing histone acetylation to induce Atoh1 (Fig. 6B). Curcumin, either on its own or in conjunction with DAPT, had no effect on the expression level of the Notch effectors Hes5 and Hey1 (data not shown)"

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813338/
       
      • Informative Informative x 1
    20. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Ok, so curcumin partially blocks Atoh1. Thanks.
       
      • Agree Agree x 2
    21. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      Seriously what's your confidence level that these substances could heal us?
       
      • Good Question Good Question x 1
    22. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      This is hard. I don't know if it is possible. But maybe it will improve something. I have lyme. I am very sick and I am desperate to improve my condition.
       
      • Agree Agree x 1
    23. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      damn, sorry to hear that.
       
    24. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
    25. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150060/figure/F0001/

      As shown in Fig. 1A, the cell viability was significantly increased by treatment with up to 2 μM Celastrol in a dose-dependent manner. However, high concentration of Celastrol (10 μM) displayed remarkable suppressive effect on cell growth, which might be due to ensued cytotoxicity.
       
    26. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
    27. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      Great.....
       
    28. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      Upgraded form od Celastrol.
      https://www.ncbi.nlm.nih.gov/m/pubmed/22343423/

      We found that liposomal celastrol had high encapsulation efficiency (71.67%) and liposomal celastrol had a higher C(max) and area under the curve, longer t(1/2), and better biodistribution than free celastrol. A cytotoxicity assay indicated that free celastrol had lower 50% inhibiting concentration values than the liposomal celastrol; however, treatment of subcutaneous xenografts with 1 mg/kg of liposomal celastrol induced greater antitumor activity than free celastrol at an equimolar concentration. In addition, a 4 mg/kg dose of liposomal celastrol had fewer severe side effects than free celastrol at the same dose. In this study, we found that the use of liposomes as a carrier of celastrol increased the bioavailability and reduced the side effects of the compound.

      So 5mg/kg is safe or not?
       
      Last edited: Oct 12, 2018
    29. JohnAdams
      Festive

      JohnAdams Member Benefactor Hall of Fame

      Location:
      Vatican
      Tinnitus Since:
      May 1st 2018
      Cause of Tinnitus:
      Aspirin Toxicity/Possibly Noise
      From what I read it is. But how could I know for sure.
       
    30. AUTHOR
      AUTHOR
      PolishSoldier87
      Moonlighting

      PolishSoldier87 Member

      Tinnitus Since:
      12/2017
      Cause of Tinnitus:
      acustic trauma, neuro-lyme/rx co-op toxins
      https://www.sciencedaily.com/releases/2008/08/080830005613.htm
      "Brigande and his colleagues were able to produce hair cells by transferring a key gene, called Atoh1, into the developing inner ears of mice. The gene was inserted along with green florescent protein (GFP) which is the molecule that makes a species of jellyfish glow. GFP is often used in research as a “marker” that a scientist can use to determine, in this case, the exact location of the Atoh1 expression. Remarkably, the gene transfer technique resulted in Atoh1 expression in the organ of Corti, where the sensory hair cells form.
      Using this method, the researchers were able to trace how the inserted genetic material successfully led to hair cell production resulting in the appearance of more hair cells than are typically located in the ears of early postnatal mice."​

      Does it mean that inducing production od Atoh1 will always cause its expression in cochlea?
       
      • Good Question Good Question x 1

Share This Page

Loading...
Similar Threads - Celastrol Enhances Atoh1
  1. JeffDamsko
    Replies:
    1
    Views:
    1,351