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NanSam
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Mon Jul 09, 2012 1:10 pm      Reply with quote
Hi, I've lurked but never posted. Does Dr. J still contribute here? I've got lots of science questions. Is this the right topic area? Thanks.
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Mon Jul 09, 2012 2:33 pm      Reply with quote
NanSam wrote:
Hi, I've lurked but never posted. Does Dr. J still contribute here? I've got lots of science questions. Is this the right topic area? Thanks.


http://barefacedtruth.com/

Hi NanSam- Dr. J doesn't post here anymore but you can go to his website link up above and send in question.

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Mon Jul 09, 2012 4:45 pm      Reply with quote
CookieD wrote:
NanSam wrote:
Hi, I've lurked but never posted. Does Dr. J still contribute here? I've got lots of science questions. Is this the right topic area? Thanks.


http://barefacedtruth.com/

Hi NanSam- Dr. J doesn't post here anymore but you can go to his website link up above and send in question.


Hi Nan (and hello also to CookieD), while it is true I don't post here regularly any more, my former students will tell you I could never resist a good science question. Go ahead and ask.

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Tue Jul 10, 2012 9:23 am      Reply with quote
DrJ wrote:
Hi Nan (and hello also to CookieD), while it is true I don't post here regularly any more, my former students will tell you I could never resist a good science question. Go ahead and ask.


I am very tempted to try a human stem cell skin product. But I also work in a biology lab so I know a bit about cytokines and I'm trying to figure out how you can control which cytokines get into the product from the stem cells. Since cytokines do so many things, how do you know their effect is a good one? Are they really safe? How are they regulated? Thanks in advance - I really appreciate your taking time to answer my questions.
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Tue Jul 10, 2012 11:26 am      Reply with quote
NanSam wrote:
DrJ wrote:
Hi Nan (and hello also to CookieD), while it is true I don't post here regularly any more, my former students will tell you I could never resist a good science question. Go ahead and ask.


I am very tempted to try a human stem cell skin product. But I also work in a biology lab so I know a bit about cytokines and I'm trying to figure out how you can control which cytokines get into the product from the stem cells. Since cytokines do so many things, how do you know their effect is a good one? Are they really safe? How are they regulated? Thanks in advance - I really appreciate your taking time to answer my questions.



Good questions all. First, if you haven’t already seen them, I would direct you to a recent series of posts at barefacedtruth.com that gets a lot deeper in terms of the science of cytokines in skin care, including issues of efficacy and safety.

http://barefacedtruth.com/2012/06/29/cytokines-in-dermal-regenerative-medicine-part-1/
http://barefacedtruth.com/2012/07/02/cytokines-in-healing-and-rejuvenation-part-2/
http://barefacedtruth.com/2012/07/03/stem-cell-factories-custom-cytokine-cocktails-part-3/
http://barefacedtruth.com/2012/07/04/cytokine-stem-cell-%E2%80%9Ctissue-of-origin%E2%80%9D-issues-part-4-an-inflammatory-view/
http://barefacedtruth.com/2012/07/06/%E2%80%9Ccytokine-facts%E2%80%9D-and-some-actual-products-part-5-of-a-series/

What we have done is compiled a knowledge base of all the cytokines most important in skin health and regeneration. We examined the world literature to determine what role functionally each key cytokine plays, at what concentration, in what sequence, for how long, and what else they stimulate in vivo (intracellular events). In our own work, we track 65 key cytokines in our mesenchymal stem cell cultures. We actually track them at several stages, because we do not just grow the cells and “take whatever shows up” as others do – we control and direct which cytokines are expressed using a proprietary method. We then study in vitro and in vivo the effects of different cocktails of cytokines on skin structure and appearance. The work is ongoing. But to answer your question, we know exactly which cytokines because we measure them, not just once but multiple times.

On the safety & efficacy issues, again it all depends. Many cytokines are important for the initial (inflammatory) phase of wound healing, but if you keep putting those into your skin day after day you end up with CSI (chronic smoldering inflammation) which is a two edged sword at best. You get plumper skin (from chronic inflammatory stimulation) but you actually accelerate aging (inflammaging). What we harvest are predominantly anti-inflammatory cytokines & growth factors, which give the benefit of soothing skin while also stimulating matrix reformation in a scarless regeneration paradigm (if you know cytokines, the key player there is TGF-beta-3). We have also written about the inflammation-carcinogenesis (I think that was part 4) issue, which is another safety related topic. E.g.:

Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Balkwill F, Charles KA, Mantovani A. Cancer Cell. 2005 Mar;7(3):211-7.

As to regulation, this is a murky area. We are pushing for more, rather than less regulation. Our labs are already fully GMP, GCP, & FDA certificated, but we think there should be more requirements for safety/efficacy testing, including actual clinical trials. Just because cytokines are natural doesn’t mean they shouldn’t be closely scrutinized. We are in the process of initiating that discussion with the FDA.

Please feel free to ask more questions. If you can, tell us about your lab’s area of interest. Do you work with stem cells?

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CookieD
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Tue Jul 10, 2012 4:32 pm      Reply with quote
Hi-I just wanted to say I have gotten rid of my milia at the corners of my mouth by using AA serum. It has been gone for over a month but I never said anything about it because there was such a push back reaction when Jom brought it up.
I have had these for years and no amount of exfoliation every got rid of them. I just saw where Sylvia said she got rid of hers also on another stem cell thread. So maybe it does have something to do with these products from some people.

My diet has stayed the same and I never use any heavy or creamy products because of my ongoing battle with acne for 35 years so I don't think it has anything to do with that. AA serum and a few acne products are all I was using at the time and had been for a couple months. It was also before I started using the ReAura laser on my face so it can't be that.

Sorry I didn't chime in Jom when you said it had gotten rid of you milia but I still had mine at the time. The only reason I said something now was because Sylvia had mentioned it on another tread.

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Tue Jul 10, 2012 4:55 pm      Reply with quote
CookieD wrote:
Hi-I just wanted to say I have gotten rid of my milia at the corners of my mouth by using AA serum. It has been gone for over a month but I never said anything about it because there was such a push back reaction when Jom brought it up.
I have had these for years and no amount of exfoliation every got rid of them. I just saw where Sylvia said she got rid of hers also on another stem cell thread. So maybe it does have something to do with these products from some people.

My diet has stayed the same and I never use any heavy or creamy products because of my ongoing battle with acne for 35 years so I don't think it has anything to do with that. AA serum and a few acne products are all I was using at the time and had been for a couple months. It was also before I started using the ReAura laser on my face so it can't be that.

Sorry I didn't chime in Jom when you said it had gotten rid of you milia but I still had mine at the time. The only reason I said something now was because Sylvia had mentioned it on another tread.


Thanks Cookie! It's amazing stuff isn't it! I never expected any product to get rid of milia but there must be something about the cytokines that makes it happen. I really hope Dr. J does a clinical trial that focuses on the use of the products to eliminate milia and other cysts.
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Tue Jul 10, 2012 6:52 pm      Reply with quote
DrJ wrote:


..... Our labs are already fully GMP, GCP, & FDA certificated, but we think there should be more requirements for safety/efficacy testing, including actual clinical trials. Just because cytokines are natural doesn’t mean they shouldn’t be closely scrutinized. We are in the process of initiating that discussion with the FDA......



Kudos!
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Tue Jul 10, 2012 8:37 pm      Reply with quote
Jom,

It was me whose milia have gone! I didnt post here as its RL and I did not want to inflame anything, but they have gone and I have also had mine since I was little and nothing has worked (apart from digging at it then cps ,lacsal and more work!)
I gave up with them!

Then the RL use and they are gone. I would have tried this line, but RL was easier to get a hold of. (UK based)
So it is obviously the cytokine/stem cell commonality. Not pretending I really know

Bad Grin

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Tue Jul 10, 2012 10:23 pm      Reply with quote
10Sylvia5 wrote:
Jom,

It was me whose milia have gone! I didnt post here as its RL and I did not want to inflame anything, but they have gone and I have also had mine since I was little and nothing has worked (apart from digging at it then cps ,lacsal and more work!)
I gave up with them!

Then the RL use and they are gone. I would have tried this line, but RL was easier to get a hold of. (UK based)
So it is obviously the cytokine/stem cell commonality. Not pretending I really know

Bad Grin


Thanks Sylvia, I knew I wasn't crazy! Laughing
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Wed Jul 11, 2012 2:05 am      Reply with quote
Hey if you are then it makes two of us!
I am soo pleased, they have gone.
But now someone just has to find a serum that changes the face I am seeing in the mirror!
That "I got no sleep face"!! Then I definitely would buy Rolling Eyes

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Wed Jul 11, 2012 8:30 am      Reply with quote
DrJ - I read through most of the resources at BFT. Very complete. Thank you for putting all that together into one place. I work in a lab that does stem cell research but related to the heart. I recognize a lot of the same issues we deal with, especially what you say about measuring cytokines and all the variables that can affect them. It's my turn to present at our weekly lab meeting, so I thought I would bring up your work and see what others think. I'm excited and ready to order the product, just want to make sure I haven't missed anything.
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Wed Jul 11, 2012 9:13 am      Reply with quote
NanSam wrote:
DrJ - I read through most of the resources at BFT. Very complete. Thank you for putting all that together into one place. I work in a lab that does stem cell research but related to the heart. I recognize a lot of the same issues we deal with, especially what you say about measuring cytokines and all the variables that can affect them. It's my turn to present at our weekly lab meeting, so I thought I would bring up your work and see what others think. I'm excited and ready to order the product, just want to make sure I haven't missed anything.


Glad to be of service. Would appreciate any feedback from your group. We invite the closest scientific scrutiny.

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Wed Jul 11, 2012 7:45 pm      Reply with quote
10Sylvia5 wrote:
Hey if you are then it makes two of us!
I am soo pleased, they have gone.
But now someone just has to find a serum that changes the face I am seeing in the mirror!
That "I got no sleep face"!! Then I definitely would buy Rolling Eyes


Actually 3 of us. I posted earlier that the small bumps in the corners of my mouth have disappeared since using Anteage.

Here is something else, may just be a coincidence but I was 8 months without a period, thinking I was almost officially menopausal, then I get an unexpected visitor after using the Anteage for about a month. Is it possible that the soy in the product ( or something else in it) is having some effect on my hormones?? What ever is going on is fine with me because those insufferable hot flashes have stopped for now.
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Wed Jul 11, 2012 8:11 pm      Reply with quote
2dagym wrote:

Here is something else, may just be a coincidence but I was 8 months without a period, thinking I was almost officially menopausal, then I get an unexpected visitor after using the Anteage for about a month. Is it possible that the soy in the product ( or something else in it) is having some effect on my hormones?? What ever is going on is fine with me because those insufferable hot flashes have stopped for now.


If I were you, I would be very concerned about your anomalous reaction, 2dagym. It seems like something hormonal that is specific to your own endocrinologic system is causing you to have a period at this time. What you describe seems to have little to do with a serum topically applied to the face. Coincidence? Maybe temporally only. But there seems to be a pre-existing endocrinological condition there and you really ought to have a full endocrinologic workup done. Just my 2 cents' worth.
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Thu Jul 12, 2012 9:09 am      Reply with quote
Sage06 wrote:
2dagym wrote:

Here is something else, may just be a coincidence but I was 8 months without a period, thinking I was almost officially menopausal, then I get an unexpected visitor after using the Anteage for about a month. Is it possible that the soy in the product ( or something else in it) is having some effect on my hormones?? What ever is going on is fine with me because those insufferable hot flashes have stopped for now.


If I were you, I would be very concerned about your anomalous reaction, 2dagym. It seems like something hormonal that is specific to your own endocrinologic system is causing you to have a period at this time. What you describe seems to have little to do with a serum topically applied to the face. Coincidence? Maybe temporally only. But there seems to be a pre-existing endocrinological condition there and you really ought to have a full endocrinologic workup done. Just my 2 cents' worth.


It's funny too because right before this happened the hot flashes were so bad that I had gotten a prescription from my gyno for low dose hormone replacement. Took it to get it filled and never picked it up because the hot flashes started to subside without it. Next thing I know the period came. I will definitely go back to the doctor and have the work up done. I wanted one anyway because of all the supplements I take, to make sure everything is ok with that as well.
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Thu Jul 12, 2012 10:11 am      Reply with quote
DrJ The anti-inflammatory-to-inflammatory cytokine balance concept was a big hit yesterday. I was asked to go back and examine some of our own data, especially about differences between mesenchymal stem cells tissue sources. A prelim excel crunch suggests our data for post-MI heart healing quality (+/- fibrosis) looks like it follows the predictions you make. Our lab director is sending you a private note on the subject through your company. He had lots of questions on the science I couldn’t answer, and wants to tell you what we are doing. Also he wants to tell you about a conference coming up in SF soon with a presentation that may put a big nail in the adipose tissue MSC equivalency coffin. Thanks for making me look good in our jlm. Being obsessed with skin care has finally paid off professionally Very Happy Can’t wait to try your products - ordering today. Nan
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Thu Jul 12, 2012 1:31 pm      Reply with quote
NanSam wrote:
DrJ The anti-inflammatory-to-inflammatory cytokine balance concept was a big hit yesterday. I was asked to go back and examine some of our own data, especially about differences between mesenchymal stem cells tissue sources. A prelim excel crunch suggests our data for post-MI heart healing quality (+/- fibrosis) looks like it follows the predictions you make. Our lab director is sending you a private note on the subject through your company. He had lots of questions on the science I couldn’t answer, and wants to tell you what we are doing. Also he wants to tell you about a conference coming up in SF soon with a presentation that may put a big nail in the adipose tissue MSC equivalency coffin. Thanks for making me look good in our jlm. Being obsessed with skin care has finally paid off professionally Very Happy Can’t wait to try your products - ordering today. Nan


Nan, I did get that e-mail, and what a delight to receive that invitation. Thanks so much for making this introduction. I may be delivering your AnteAGE in person!

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Thu Jul 12, 2012 1:54 pm      Reply with quote
10Sylvia5 wrote:
Hey if you are then it makes two of us!
I am soo pleased, they have gone.
But now someone just has to find a serum that changes the face I am seeing in the mirror!
That "I got no sleep face"!! Then I definitely would buy Rolling Eyes


OK, get ready for the "I got no sleep face" serum. It's AnteAGE. This study was just published:

Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. by the Salk Institute team.

What is says in essence is that sleep deprivation flips a switch to create inflammatory cytokines. Chronically, these lead to diseases, and accelerated aging of skin. A cocktail of anti-inflammatory cytokines that pushes the balance back, away from inflammatory, should be a good counter to "I got not sleep" faces. This is what AnteAGE delivers.

Here is the study abstract.

Proc Natl Acad Sci U S A. 2012 Jul 9.

Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines.

Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037.
Abstract

Chronic sleep deprivation perturbs the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases, thus raising a hypothesis that circadian-oscillator components may regulate immune response. Here we show that absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF-κB and protein kinase A (PKA) signaling activation in Cry1(-/-);Cry2(-/-) cells. We further demonstrate that increased phosphorylation of p65 at S276 residue in Cry1(-/-);Cry2(-/-) cells is due to increased PKA signaling activity, likely induced by a significantly high basal level of cAMP, which we detected in these cells. In addition, we report that CRY1 binds to adenylyl cyclase and limits cAMP production. Based on these data, we propose that absence of CRY protein(s) might release its (their) inhibition on cAMP production, resulting in elevated cAMP and increased PKA activation, subsequently leading to NF-κB activation through phosphorylation of p65 at S276. These results offer a mechanistic framework for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases.

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Thu Jul 12, 2012 2:03 pm      Reply with quote
that make sense with the book Im reading,linking lack of sleep, lack of the right nutrients, directly with wrinkles and chronic inflammation and disease, even more so than UV damage and smoking.

You just need to sell it in the UK!!!

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Thu Jul 12, 2012 2:18 pm      Reply with quote
10Sylvia5 wrote:
that make sense with the book Im reading,linking lack of sleep, lack of the right nutrients, directly with wrinkles and chronic inflammation and disease, even more so than UV damage and smoking.

You just need to sell it in the UK!!!


Ask and you shall receive. I believe we begin selling in the UK (and a lot of other countries worldwide) today or tomorrow. We have an EU website coming online, as well as Latin America.

Oh, and PayPal is up and running.

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Thu Jul 12, 2012 2:22 pm      Reply with quote
Hey nice one!
However did you manage it?

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Thu Jul 12, 2012 2:29 pm      Reply with quote
10Sylvia5 wrote:
that make sense with the book Im reading,linking lack of sleep, lack of the right nutrients, directly with wrinkles and chronic inflammation and disease, even more so than UV damage and smoking.

You just need to sell it in the UK!!!


UV damage and smoking. It's all about the cytokines.

Am J Respir Cell Mol Biol. 2012 Jul;47(1):67-79.


Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.


Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD.

PS the best antagonists to pro-inflammatory cytokines are anti-inflammatory cytokines.

Photochem Photobiol. 2012 May 26.

Inflammasome Activation of IL-1 Family Mediators in Response to Cutaneous Photodamage

Although keratinocytes are relatively resistant to ultraviolet radiation (UVR) induced damage, repeated UVR exposure result in accumulated DNA mutations that can lead to epidermal malignancies. Keratinocytes play a central role in elaborating innate responses that lead to inflammation and influence the generation of adaptive immune responses in skin. Apart from the minor cellular constituents of the epidermis, specifically Langerhans cells and melanocytes, keratinocytes are the major source of cytokines. UVR exposure stimulates keratinocytes to secrete abundant pro-inflammatory IL-1-family proteins, IL-1α, IL-1β, IL-18, and IL-33. Normal skin contains only low levels of inactive precursor forms of IL-1β and IL-18, which require caspase 1-mediated proteolysis for their maturation and secretion. However, caspase-1 activation is not constitutive, but dependents on the UV-induced formation of an active inflammasome complex. IL-1 family cytokines can induce a secondary cascade of mediators and cytokines from keratinocytes and other cells resulting in wide range of innate processes including infiltration of inflammatory leukocytes, induction of immunosuppression, DNA repair or apoptosis. Thus, the ability of keratinocytes to produce a wide repertoire of proinflammatory cytokines can influence the immune response locally as well as systematically, and alter the host response to photodamaged cells. We will highlight differential roles played by each IL-1 family molecule generated by UV-damaged keratinocytes, and reveal their complementary influences in modulating acute inflammatory and immunological events that follow cutaneous UV exposure.

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Thu Jul 12, 2012 2:31 pm      Reply with quote
10Sylvia5 wrote:
Hey nice one!
However did you manage it?


Bribery. We sent some to HRHQE2. Great for mature skin. Cool

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Thu Jul 12, 2012 2:35 pm      Reply with quote
So will we get the samples in UK then?

I'm very pleased to hear about the postage to UK. Will you be able to set up UK based distribution? The customs charges are a killer - and they add an annoying £8 'handling fee' on top the customs - as if they have done us a favour by stopping our items and charging us more!!
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