28 replies to this topic

[Phoenicis]

So I thought I would share my experiences here so that others might benefit from them too. For those of you who do not know psoriasis is a chronic autoimmune disease that causes red patches on the skin.

My experience with the disease started when I was 19, one summer I was dating a really neurotic girl and the relationship caused me to experience a lot of stress, I was also a smoker and drank quite a lot. I was asked to get my chest waxed, so I went to a waxing studio and had a full chest and stomach waxing done. The next day my entire chest and stomach were covered in in red dots. Over the course of that week this dots turned into small patch and quickly spread all over my body including the palms of my hands and my feet. My mother also suffers from the condition (its genetic) and she provided me with her UV light which is used for treating it.

This had little effect and in the coming weeks this disease ruined my life. I tried everything to hide the spots on my hands, but the anxiety caused me to become a different person and I missed a scholarship opportunity as a result. My parents and I soon decided that something had to be done, we found a doctor in Munich, Germany working at a university clinic for psoriasis. He was well recognized in this field. After advising me that disease was inherited an incurable he recommended I undergo a complete tonsillectomy as well as full body UV light therapy. The light therapy help a little, but the tonsillectomy was a breakthrough. Literally all of my patches disappeared, most of my remaining light therapy treatments were cancelled because there was no longer any need.

Of course this is not the end of the story, 3 years later I began to smoke again, I quit after my operation but took it up again. Patches of psoriasis returned on my elbows, leg and the corner of my nose. I treated these with topical steroids and a UV light. The disease remained despite my efforts and when I moved from a warm climate into a cold one year ago, it began to spread once again.

The sight of the disease was to me unbearable so I decided to do something. I quit smoking again but this did not produce any noticeable effects. At that point I knew I needed to try something so let me outline what I came up with. My approach is to lower overall inflammation so that existing patches can be treated effectively.

Diet - I decided to eliminate as many inflammatory compounds from my food as possible. This is a great article on the role of diet in psoriasis, I would encourage anyone interested to get the full text version. I found the only way to do this was by adopting a vegan diet, as these have been shown to improve rheumatoid arthritis. The compound I wanted to avoid the most:

arachidonic acid:

Dietary sources of this inflammatory compound include chicken, beef and other meats as well as eggs.

This compound has also made researchers interested in high dihomogammalinolenic acid, which seems reduce its effects as well as high intake of eicosapentaenoic acid (EPA), which seems to have mixed results.

• http://onlinelibrary...05.06781.x/full
• http://europepmc.org...CG1uwaZitp9k.12
• http://www.pnas.org/...2/12/5130.short
• http://www.google.co...s/US20120302632

Gluten

Should be avoided since Celiac disease could be related to psoriasis:

• http://0www.scienced...738081X10000519
• http://0www.scienced...002927003017179
• http://0informahealt...365520600633529

• By pursuing this diet I also avoid excessive methionine, which can help with life extension as well. Methionine
  
• http://archderm.jama...rticleid=528773
• http://jn.nutrition....134/4/825.short
• http://www.ncbi.nlm....pubmed/18789600

With overall lower inflammation I was more confident in using a multi-pronged approach to treating the psoriasis because I believed it would respond better once overall inflammation is lower.


Epigenetic Agents

• Curcumin and resveratrol act synergistically to suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway, suppressing the activity of Th1 and Th2 cells and inhibiting production of proinflammatory cytokines (more in this study and more on why this matters)

Oral Supplementation:

• Algae Omega 3 EPA/DHA as mentioned earlier
• I will soon try gamma-linolenic acid - "increases the content of its elongase product, dihomo-gamma-linolenic acid (DGLA) ... DGLA can be converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1. This is noteworthy because these compounds possess both anti-inflammatory and antiproliferative properties."
• Vitamin D ( I take 5000 iu D3 every night)– oral vitamin D can improve psoriasis in some patients, this thought to be dependent on allele variations in vitamin D receptor genes.
• Vitamin b12 – necessary for vegans and psoriasis plaques have low levels of this vitamin

Topical treatments:

• Retinoic Acid – I recently started using tretinoin gel from AlldayChemist. I have seen a huge improvement in my skin. The side of my nose which was always red is now clearing and the skin is starting to look normal. Following my initial psoriasis outbreak I noticed that overall my skin had changed. It seemed a lot more prone to clogged pores and ingrown hairs. The tretinoin gel seems to be reversing that.
• Tazarotene (a class of retinoids) – I will start using this soon as it is an effective option, and may be more effective than tretinoin.
• Vitamin D and B12 creams can be used where retinoic acid is unsuitable and can be used with light therapy. They are both effective.
• I avoid topical steroids as I feel these are too harsh

My observation has been that once inflammation is low the disease will no longer spread quickly and is much more manageable. My topical treatments and supplements have been much more effective after changing my diet and habits. I am currently almost completely cleared psoriasis and have found this strategy to be successful after years of struggling. I really like retinoic acids because the seem to reverse what topical steroids and this disease have done to my skin.

Edit: Spelling, by request -mod

Edited by niner, 12 March 2014 - 03:13 PM.

[LexLux]

awesome

Edited by LexLux, 12 March 2014 - 12:16 AM.

[Phoenicis]

Seems two of the studies I linked don't work:

1) on psoriasis and diet + treatments (which I recommended) also cited for vitamin D and b12 creams etc:

• http://www.cidjourna...0051-9/abstract

2) On vegetarian diet & psoriasis (I went vegan as dairy products increase cholesterol and inflammation)

• http://www.ncbi.nlm..../pubmed/1681264
• http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2005.06781.x/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+Saturday%2C+15+March+from+10%3A00-12%3A00+GMT+%2806%3A00-08%3A00+EDT%29+for+essential+maintenance&userIsAuthenticated=false&deniedAccessCustomisedMessage=
• http://europepmc.org/abstract/MED/6197838

Edited by Phoenicis, 12 March 2014 - 12:41 AM.

[Phoenicis]

I also forgot to emphasize in my first post how much of a difference changing my diet made. I saw my patches go from flaming red and swollen to flat and slightly pink. Many of them actually disappeared on their own. Those that did not are now responding very quickly to tretinoin and the other supplements. No one can even tell I have the disease now, even my current partner has not noticed any of my remaining spots. There are just two tiny spots on my elbows left, my nose has cleared.

Edited by Phoenicis, 20 March 2014 - 09:35 PM.

[blood]

Fascinating.

I wonder if you would benefit from C60-olive oil?

[Major Legend]

Can these treatments help with eczema?

[niner]

Can these treatments help with eczema?

C60-oo eliminated my eczema. I'd been unable to get rid of it for about a decade prior, so I was pretty impressed by this result. I don't know if it would work for psoriasis or not.

[Major Legend]

Can these treatments help with eczema?

C60-oo eliminated my eczema. I'd been unable to get rid of it for about a decade prior, so I was pretty impressed by this result. I don't know if it would work for psoriasis or not.

hows that possible? and where can I get C60? Do you have to take it daily?

[niner]

Can these treatments help with eczema?

C60-oo eliminated my eczema. I'd been unable to get rid of it for about a decade prior, so I was pretty impressed by this result. I don't know if it would work for psoriasis or not.

hows that possible? and where can I get C60? Do you have to take it daily?

I suspect the mechanism is inhibition of allergic mediator release, although C60's antioxidant properties might be involved. The form that people are using is a lipid adduct commonly known as C60-olive oil. You can get it from Sarah Vaughter (c60antiaging.com) or carbon60oliveoil.com. You don't need to take it every day because it has a very long half life. If I stop taking it for a long time, my eczema eventually returns, but I'd take it even if it didn't help eczema, since it has many other benefits that I like.

[aribadabar]

C60-oo eliminated my eczema.

How long did it take for C60-oo to remove the eczema? And what was the dosage during this period?

Thanks!

[Invariant]

C60-oo eliminated my eczema.

How long did it take for C60-oo to remove the eczema? And what was the dosage during this period?

Thanks!

I have pretty much the same experience as Niner, and for me it took maybe a few days before the eczema cleared up. I take 2 droppers of 1.875ml containing 1.5mg of C60 each, once every ~2 days. If I don't take it for a few days, the eczema comes back, but I know Niner uses a mega-dosing scheme that allows him to take C60 once every few weeks only.

[Phoenicis]

Some updates and additional insights -

 

I am now using one additional epigenetic agent -

 

Butyrate: "Butyrate is a short chain fatty acid derived from the microbial fermentation of dietary fibers in the colon. In the last decade, multiple beneficial effects of butyrate at intestinal and extraintestinal level have been demonstrated. The mechanisms of action of butyrate are different and many of these involve an epigenetic regulation of gene expression through the inhibition of histone deacetylase. [...] The principle mechanisms through which butyrate exerts its anti-inflammatory effects are the suppression of nuclear factor B (NFkB) activation, the inhibition of interferon g production and the upregulation of peroxi- some proliferator-activated receptor g (PPARg), which may result from the inhibition of HDAC..."

 

Good sources of butyrate are fibers like FOS and RS (resistant starch), lots of people use Bobs Red Mill Potato Starch; I use both FOS and RS and in addition I try to consume fruits and vegetable high in fiber.

 

A quick google scholar search confirms interest in butyrate for the treatment of psoriasis:

 

• Histone deacetylase inhibitors in psoriasis therapy
• F McLaughlin, T NBLa - Current Drug Targets-Inflammation & …, 2004 - ingentaconnect.com

• [The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo
• F Leoni, G Fossati, EC Lewis, JK Lee, G Porro… - Molecular …, 2005 - ncbi.nlm.nih.gov

• Histone deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases
• SJ Shuttleworth, SG Bailey… - Current drug …, 2010 - ingentaconnect.com
• Table 2 : Immunomodulatory effects of deacetylase inhibitors
• www.nature.com ›  ›  ›  › ‎

Additional benefits of butyrate include enhanced memory & synaptic plasticity, neuron developmental plasticity and it is also being investigated for cancer. 

Currently I am investigating how butyrate may interact with other epigenetic agents such as resveratrol, curcumin and ECGC. It seems that interaction have only really been studied in relation to cancer therapies, where varying interactions are documented.

 

 

Edited by Phoenicis, 16 April 2014 - 02:35 AM.

[niner]

C60-oo eliminated my eczema.

How long did it take for C60-oo to remove the eczema? And what was the dosage during this period?

Thanks!

I had a large batch of home-brew that I think oxidized over time, and it lost the anti-eczema activity. I'm getting set up to make a new batch, but not wanting to wait, I bought a 30ml bottle from carbon60oliveoil.com, and consumed the whole thing with a couple meals two weeks ago. The eczema improvement was very rapid, noticeable within a day or two, and gradually improving. It's now completely resolved. I think this dose will probably be good for 4-6 weeks, although I'm planning on sticking with my monthly schedule for the time being. This isn't a "cure", in the sense that you can stop taking c60 and the eczema will be gone forever, but as long as I'm using a good quality c60, I have essentially no evidence of eczema, and no need for the topical steroids that seemed like they were going to be my life-long companion. I'm not aware of any oral pharmaceuticals that can do this, other than very potent steroids with a boatload of side effects. Honestly, c60 feels like a miracle drug to me.

For the next batch, I'll be taking steps to exclude oxygen and retard any and all forms of degradation.

[Phoenicis]

 

 

C60-oo eliminated my eczema.

How long did it take for C60-oo to remove the eczema? And what was the dosage during this period?

Thanks!

 

I had a large batch of home-brew that I think oxidized over time, and it lost the anti-eczema activity. I'm getting set up to make a new batch, but not wanting to wait, I bought a 30ml bottle from carbon60oliveoil.com, and consumed the whole thing with a couple meals two weeks ago. The eczema improvement was very rapid, noticeable within a day or two, and gradually improving. It's now completely resolved. I think this dose will probably be good for 4-6 weeks, although I'm planning on sticking with my monthly schedule for the time being. This isn't a "cure", in the sense that you can stop taking c60 and the eczema will be gone forever, but as long as I'm using a good quality c60, I have essentially no evidence of eczema, and no need for the topical steroids that seemed like they were going to be my life-long companion. I'm not aware of any oral pharmaceuticals that can do this, other than very potent steroids with a boatload of side effects. Honestly, c60 feels like a miracle drug to me.

For the next batch, I'll be taking steps to exclude oxygen and retard any and all forms of degradation.

 

 

Hi Niner, do you know anything about how the fullerenes from c-60 interact with other substances like curcumin and small molecules like resveratrol? I am wondering if they increase bioavailability? Could they work like nano-particles for delivery of those compounds?

 

[Phoenicis]

Can these treatments help with eczema?

 

Maybe!

 

[Darryl]

There's an interesting literature on rapamycin and psoriasis:

 

Reitamo, Sakari, et al. "Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial." British journal of dermatology145.3 (2001): 438-445.

Ormerod, A. D., et al. "Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double‐blind trial." British Journal of Dermatology 152.4 (2005): 758-764.

Frigerio, E., et al. "Severe psoriasis treated with a new macrolide: everolimus."British journal of dermatology 156.2 (2007): 372-374.

Buerger, C., et al. "Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin." British Journal of Dermatology 169.1 (2013): 156-159.

 

Another rapamycin analog is approved for eczema. 

 

Vegan diets are likely to have lower leucine, are known to reduce free IGF-1, and some would reduce insulin, so perhaps some attenuation of mTOR signalling is also contributing to the OPs results.

[Phoenicis]

Nice find there Darryl, always a good strategy to look at the drug studies since this is where funding is available!

 

"The mTOR pathway has been shown to play a role in regulating the immune response, not only in myeloid cells but also in keratinocytes,[4] and potentially contributes to cytokine production in psoriasis.[5] As psoriasis is also considered a hyperproliferative disorder, thus requiring enhanced cell growth, we examined the activation status of mTOR signalling in psoriatic lesions. We report for the first time an increase in mTOR expression and phosphorylation in lesional and nonlesional psoriatic skin compared with healthy skin. In addition, mTOR is hyperphosphorylated in the basal layer of lesional skin. Moreover, ribosomal protein S6 was found to be activated in suprabasal, differentiating layers of lesional psoriatic skin. This suggests a role of mTOR signalling in the pathogenesis of psoriasis."

[...]

"Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs."

 

So leucine restriction (possible via vegan diet / low protein) -> less mTOR. That's definitely noteworthy. 

 

The only real research that I could find for HDAC inhibitors involved studies on drugs like vorinostat. However a quick glance at the side effects definitely reminds me of why I choose to go with fiber (FOS & RS) -> butyrate -> HDAC inhibition

 

http://jn.nutrition....33/7/2485S.full

 

"One additional, key discovery over recent years relevant to this therapeutic area is that HDAC1 is overexpressed in psoriatic skin, suggesting a role for HDAC1 inhibitors for the treatment of psoriasis and related inflammatory skin disorders"

 

 

 

Edited by Phoenicis, 26 April 2014 - 10:40 PM.

[Soma]

Good sources of butyrate are fibers like FOS and RS (resistant starch), lots of people use Bobs Red Mill Potato Starch; I use both FOS and RS and in addition I try to consume fruits and vegetable high in fiber.
  

There are supplemental forms of butyrate, although I don't know how well they work. Have you tried any of them? There are calcium/magnesium butyrate compounds as well as sodium butyrate.

[Phoenicis]

I wanted to quote these posts from a cool thread to address the butyrate issue. In short, I'm not sure whether it would be preferable or not. It seems supplements like Na Butyrate could be cheap (compared to drugs maybe not RS or FOS) additions/alternatives, but I'd like to know more as well.

 

In addition Celebes seems to show that butyrate will increase epigenome plasticity, which I find inguiging. As Tree notes, methyl groups are reduced in favor of acetyl groups. He considers that this is similar to erasing epigenetic changes which occured throughout life. Sounds intruiging.

 

Plasticity almost sounds like other epigenetic agents including curcumin, resveratrol and ECGC may be more effective. I am just starting a course on epigenetics on coursera and look forward to investigating this further.

Celebes proposed sodium butyrate as alternative for vorinostat. There is indeed research suggesting that it can extinguish fear in a similar manner to vorinostat and it's cheaper. However it is also a horrible smelling substance used as a stinkbomb and requires a higher dose than vorinostat. [...]

[...]

 

2] The second problem is the notion that butyric acid can do all that vorinostat and cl-994 can do yet it was never discovered before! That is what literature is saying, and yet... it's a bit like claiming carrots is as good as prozac yet nobody ever noticed. I guess it's *possible* but... it sounds too much like all the other hyped claims I read about supplements.
 

I don't understand how you get from an established property of a compound seen in study after study to... supplement hype. Oh right: how can a relatively "ordinary" substance have any effect on something as powerful as plasticity. Comparing two things that have the exact same effect at different doses to the difference between carrots and prozac is pretty ridiculous. You seem to need to believe that HDAC inhibition is somehow "special" in order to feel hopeful about it. 

 

 

i. Butyrate producing bacteria have the exact same effect on plasticity vorinostat does: 

 

Heijtz et al. showed that SPF mice had higher central expression of neurotrophins, such as nerve growth factor (NGF) and BDNF. Furthermore, there was differential expression of multiple genes involved in the secondary messenger pathways and synaptic long-term potentiation in the hippocampus, frontal cortex and striatum. Similarly, Neufeld et al. demonstrated increased expression of NMDA receptor subunit NR2B in the central amygdala and serotonin receptor 1A (5-HT 1A) expression in the hippocampus in SPF mice compared to germ-free mice.

 

ii. And almost exactly the same effect on Histone H3 acetylation and GDNF that Valproate does:

 

http://www.ncbi.nlm....9941/figure/F4/

http://www.ncbi.nlm....9941/figure/F3/

 

 

iii. And is the only other HDAC inhibitor shown to facilitate complete fear extinction (apart from vorinostat and valproate):

 

http://www.ncbi.nlm....port=objectonly

 

 

The others are prescription drugs so they must be more effective, all evidence to the contrary? More than a little irrational.

 

 

Also, you need to realise that neither vorinostat, butyrate nor valproate cause fear extinction. They increase plasticity allowing other therapies to overcome the imprinting. To my mind, increasing plasticity over time scales that neurogenesis operates over should be more effective than ramping up plasticity for a few hours and hoping whatever you do in that period sticks. You can get 2 months of RS(butyrate), magnesium threonate and baclofen (all shown to either promote plasticity and/or fear extinction) for the price of 1 (half) dose of vorinostat and without any risk of customs seizure. I know what I'm going for.

 

[...]

Information is stored in the epigenome in several forms, among them are methyl and acetyl groups. HDAC inhibition forces the removal of methyl groups in favour for acetyl groups. This unlocks genes but some are locked for a good reason. If you take a lot of HDAC inhibitiors, it will start to unlock *all* locked genes. Which can cause cancer or other problems.

 

Whether you call this resetting is semantics. Since the epigenome carries information of your entire life (and some of those of your ancestors) which gets erased when you start to inhibit HDACs I think it is an appropriate term.

 

That window of learning you mentioned is caused by the removal of the off-switches in your epigenome. Especially fear and anxiety is under protective lock; the bran doesn't want them removed easily. Once the read/write protection is gone you can change the memory.

 

So my statement was correct and so is yours.

 

 

Anyway: I ordered 2 dosages of vorinostat in a group buy yesterday. Will come back when I used it.

 

 

Edited by Phoenicis, 28 April 2014 - 10:23 PM.

[Phoenicis]

miR-21 - Another good target?

 

"In the case of psoriasis, it was already known that the miR-21 was much more abundant in psoriatic skin than in healthy skin. To investigate its role, the researchers inhibited miR-21 first in the mouse model using compounds obtained from Santaris Pharma (Denmark), and saw how the symptoms disappeared in a short period of time with no apparent side effects.

The next step was to work with human samples. The authors grafted skin samples from a dozen patients onto live mice -- a xeno-transplantation strategy (PDX-patient-derived xeno-transplants) that allows researchers to study the reaction of human tissue in vivo without treating the patient -- and treated the lesions locally with the compound that blocks miR-21. "The results have been very positive and are encouraging, given that this would be a totally innovative way of treating psoriasis," says Guinea-Viniegra."

 

Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer

G Mudduluru, J George-William, S Muppala… - Bioscience …, 2011 - bioscirep.org

 

Synopsis

 

"Curcumin has promising potential in cancer prevention and therapy by interacting with proteins and modifying their expression and activity, which includes transcription factors, inflammatory cytokines and factors of cell survival, proliferation and angiogenesis. miR-21 is overexpressed in many tumours, promoting progression and metastasis. In the present study, we examined the potential of curcumin to regulate miR-21, tumour growth, invasion and in vivo metastasis in colorectal cancer. In Rko and HCT116 cells, we identified two new transcriptional start sites of the miR-21 gene and delineated its promoter region. PMA stimulation induced miR-21 expression via motifs bound with AP-1 (activator protein 1) transcription factors. Curcumin treatment reduced miR-21 promoter activity and expression in a dose-dependent manner by inhibiting AP-1 binding to the promoter, and induced the expression of the tumour suppressor Pdcd4 (programmed cell death protein 4), which is a target of miR-21. Curcumin-treated Rko and HCT116 cells were arrested in the G₂/M phase with increasing concentrations. Furthermore, curcumin inhibited tumour growth, invasion and in vivo metastasis in the chicken-embryo-metastasis assay [CAM (chorionallantoic membrane) assay]. Additionally, curcumin significantly inhibited miR-21 expression in primary tumours generated in vivo in the CAM assay by Rko and HCT116 cells (P<0.00006 and P<0.035 respectively). Taken together, this is the first paper to show that curcumin inhibits the transcriptional regulation of miR-21 via AP-1, suppresses cell proliferation, tumour growth, invasion and in vivo metastasis, and stabilizes the expression of the tumour suppressor Pdcd4 in colorectal cancer."

 

 

Here are some studies covering other effects I managed to find -

 

 

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials -

 

The authors of this study concluded that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity and that the anti-psoriatic activity of curcumin may be achieved through modulation of PhK activity [(1)]

 

Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters.Heng MC, Song MK, Harker J, Heng MKBr J Dermatol. 2000 Nov; 143(5):937-49.

 

Curcumin attenuates the expression of IL-1β, IL-6, and TNF-α as well as cyclin E in TNF-α-treated HaCaT cells; NF-κB and MAPKs as potential upstream targets

JW Cho, KS Lee, CW Kim - … journal of molecular …, 2007 - spandidos-publications.com

 

TNF-α induces some proinflammatory cytokines including IL-1β, IL-6, IL-8, and itself by activation of NF-κB or MAPKs (p38, JNK, ERK). These cytokines play important roles in various inflammatory skin diseases, such as psoriasis. Recently it was also reported that expression of cyclin E is up-regulated by ERK pathway after TNF-α treatment. However, it was unknown whether curcumin, showing inhibitory effects on NF-κB and MAPKs, attenuates the expression of TNF-α-induced IL-1β, IL-6, IL-8, and TNF-α as well as cyclin E expression in HaCaT cells. In this study, we investigated the inhibitory effect of curcumin on expression of proinflammatory cytokines and cyclin E in TNF-α-treated HaCaT cells. We found that curcumin inhibited the expression of TNF-α-induced IL-1β, IL-6, and TNF-α, but not IL-8, in TNF-α-treated HaCaT cells as well as the TNF-α-induced cyclin E expression. In addition, curcumin inhibited the activation of MAPKs (JNK, p38 MAPK, and ERK) and NF-κB in TNF-α-treated HaCaT cells. Taken together, curcumin exerts anti-inflammatory and growth inhibitory effects in TNF-α-treated HaCaT cells through inhibition of NF-κB and MAPK pathways.

 

UVB-induced IL-18 production in human keratinocyte cell line NCTC 2544 through NF-κB activation

A Grandjean-Laquerriere, F Antonicelli, SC Gangloff… - Cytokine, 2007 - Elsevier

 

In the present study, we investigated the implication of NF-κB in the production of pro-inflammatory cytokine IL-18 by human keratinocytes stimulated by UVB. We demonstrated that NCTC 2544 keratinocyte cell line irradiated by UVB enhanced the IL-18 mRNA and protein secretion under its bioactive form. Overexpression of IL-18 by UVB irradiation was accompanied by NF-κB transcription factor activation using specific IL-18 gene sequence corresponding to NF-κB DNA binding site. The relationship between these transcription factors and IL-18 expression was confirmed using curcumin and PDTC, two inhibitors of NF-κB. Our results show that UVB and curcumin or PDTC co-treatment led to a down-regulation of IL-18 expression associated with an inhibition of NF-κB DNA binding. Hence, our results demonstrated that this transcription factor is implicated in biologically active IL-18 production by human keratinocytes irradiated by UVB.

 

 

I checked for curcumin this time but will also post more on resveratrol. The key with curcumin seems to be achieving bioavailability. In relation to bioavailability I like the recent study bellow which was financed by the German Government. Theracurmin looks great but is expensive, BCM-95 did ok.

 

Schiborr, C., Kocher, A., Behnam, D., Jandasek, J., Toelstede, S. and Frank, J. (2014), The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol. Nutr. Food Res., 58: 516?527. doi: 10.1002/mnfr.201300724
http://onlinelibrary....201300724/full

"The use of adjuvants, such as piperine [28] or turmeric essential oils [37], enhanced curcumin bioavailability (based on AUC) 20- or 7-fold, respectively (Table 5). Incorporation of curcumin into lecithin (mainly phosphatidylcholine) liposomes resulted in a ca. fourfold better absorption (based on AUC) than native curcumin in nine healthy volunteers [38]. The bioavailability of a micronized form of crystalline curcumin (Theracurmin, prepared from curcumin, ghatti gum, and water), compared to native curcumin, was 27-fold increased (Table 5) [39]. Thus, our micellar delivery system, which enhanced curcumin bioavailability 185-fold (all subjects), appears to be superior to all hitherto tested formulations, while our micronisate (ninefold increase in AUC) is similarly effective as previously reported strategies (Table 5). Furthermore, the C_max achieved with a single oral dose of 410 mg curcumin from our micellar formulation (women, 3.7 ?mol/L; men 2.6 ?mol/L) are higher than those observed after the intake of 8 g of native curcumin [31].

The present study revealed sex differences with respect to the plasma AUC of curcumin. Women absorbed curcumin to a larger extent (higher C_max and AUC) than men (Table 2). This could be due to the reportedly higher expression and activity of the hepatic drug efflux transporter P-glycoprotein (MDR1) and some isoforms of the glucuronosyltransferases and sulfotransferases, enzymes involved in curcumin biotransformation, in men [47]. However, the differences in bodyweight (Table 1), blood volume, and body fat, which ultimately lead to smaller volumes of distribution in women, may also account for the observed differences [47].

Less than 0.2% of the oral dose of curcumin was excreted with urine within 24 h. Thus, >98.8% of the ingested curcumin was either excreted via the bile and feces or may have been distributed to body tissues where it may potentially exert biological activities.

Free curcumin concentrations as low as 100 nmol/L reversed disease state and reduced IL-1? in Alzheimer's disease models [48, 49], therefore our newly developed curcumin formulations may be suitable vehicles for the delivery of pharmacologically relevant doses of the phytochemical in human intervention trials."

 

[Soma]

A few more resources that you may already have researched. Forgive me if you've come across any of this already. I have had my fair share of skin problems, so I have done a lot of research. The following are all easily obtainable.

Polypodium leucotomos extract

Role of oral Polypodium leucotomos extract in dermatologic diseases: a review of the literature.

Abstract
Polypodium leucotomos extract (PLE), derived from the tropical fern of Polypodiaceae family, has properties ranging from immunomodulatory and antioxidative to photoprotective. It is these multiple mechanisms of action, in combination with a favorable side effect profile, which makes PLE a promising adjunctive treatment for several dermatologic disorders. Studies are summarized on the use and potential applications of PLE in the treatment or management of photodermatoses, vitiligo, melasma, psoriasis, atopic dermatitis, and more recently, in minimizing infections in high-performance athletes. More data, however, with larger sample sizes are needed to confirm these benefits..

Nigella sativa extract:

Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds.

Abstract
BACKGROUND:
Nigella sativa Linn (Ranunculaceae) is popularly known as black cumin with a wide spectrum of pharmacological activities including anti-inflammatory, antibacterial, antifungal and antihelmenthic. The seeds are externally applied for eruptions of skin. The seeds are used traditionally for psoriasis tropicus with general pain and eruption of patches.
OBJECTIVE:
The ethanolic extract of Nigella sativa seeds were evaluated for antipsoriatic activity.
MATERIALS AND METHODS:
The screening of antipsoriatic activity of 95% of ethanolic extract of Nigella sativa seeds by using mouse tail model for psoriasis and in vitro antipsoriatic activity was carried out by SRB Assay using HaCaT human keratinocyte cell lines.
RESULTS:
The ethanolic extract of Nigella sativa seeds extract produced a significant epidermal differentiation, from its degree of orthokeratosis (71.36±2.64) when compared to the negative control (17.30±4.09%). This was equivalent to the effect of the standard positive control, tazarotene (0.1%) gel, which showed a (90.03±2.00%) degree of orthokeratosis. The 95% ethanolic extract of Nigella sativa shown IC50 239 μg/ml, with good antiproliferant activity compared to Asiaticoside as positive control which showed potent activity with IC50 value of 20.13 μg/ml.
CONCLUSION:
The ethanolic extract of Nigella sativa seeds also showed increase in relative epidermal thickness when compared to control group by confirming its traditional use in psoriasis treatment.

Indigo naturalis extract:

Indigo naturalis upregulates claudin-1 expression in human keratinocytes and psoriatic lesions.

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Indigo naturalis is used in traditional Chinese medicine to treat various dermatoses. Our previous clinical studies showed that indigo naturalis is an effective treatment for psoriasis. Herein, the capabilities of indigo naturalis extract and its derivatives to increase claudin-1 expression and tight junction (TJ) function in human keratinocytes and psoriatic lesions were further studied.
MATERIALS AND METHODS:
Claudin-1 expression in psoriatic plaques with or without indigo naturalis treatment was analyzed by immunohistochemical methods. In primary human keratinocytes, the expression of claudin-1 was analyzed by fluorescent immunostaining, a real-time RT-PCR, and Western blot analysis. The effect of indigo naturalis on TJs was evaluated by measuring the transepithelial electrical resistance (TEER) and paracellular tracer flux.
RESULTS:
The indigo naturalis extract upregulated mRNA and protein expressions of claudin-1 and function of TJs in primary human keratinocytes in concentration-dependent manners. Its main components, indirubin, indigo, and tryptanthrin, exerted synergistic effects on upregulating TJ functions in primary human keratinocytes. In addition, indigo naturalis increased the activity of protein kinase C (PKC), and a known potent PKC inhibitor, Ro318220, attenuated the indigo naturalis-induced claudin-1 expression. Significantly, restoration of claudin-1 was observed in healed psoriatic lesions after indigo naturalis treatment.
CONCLUSIONS:
Indigo naturalis upregulates claudin-1 expression and restores TJ function in keratinocytes. Our data also suggest that indirubin, indigo, and tryptanthrin have a synergistic effect on TJ function.

Mahonia aquifolium (Oregon Grape):

Mahonia aquifolium in patients with psoriasis vulgaris - an intraindividual study.

Abstract
Psoriasis vulgaris is a skin disease with a multi-factorial genesis where no causal treatment is known. Based on our own pilot studies, we set up a randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of Mahonia aquifolium bark extract in psoriasis patients. From autumn 1990 to spring 1992 we treated 82 patients of all severity gradings, recruited by 22 family physicians. Patients were told to apply two types of ointment (verum/ placebo) one to the left side of their body the other to the right. After an average treatment period of four weeks, patients as well as physicians assessed the therapy's success on a three-level ordinal rating scale. Statistically significant differences (α = 5%) could be found for patients' but not for physicians' assessments. Additional analyses show that treatment differences are not significantly masked by parallel antipsoriatic therapies. Adverse drug reactions, such as itching and burning sensations and "allergic reactions,' occured in four patients. Therefore, we regard Mahonia aquifolium bark extract as a potent and safe therapy of moderately severe cases of psoriasis vulgaris.

Treatment of mild to moderate psoriasis with Reliéva, a Mahonia aquifolium extract--a double-blind, placebo-controlled study.

Abstract
Psoriasis is usually treated with local and systemic medications that have varying degrees of efficacy and safety profiles. We investigated the efficacy and safety of an alternative treatment from natural sources, Mahonia aquifolium, for the management of mild to moderate psoriasis. Two hundred subjects participated in a randomized, double-blind, placebo-controlled study using either the topical cream Reliéva (a homeopathic product containing a proprietary M. aquifolium extract) or control (placebo) twice a day for 12 weeks. Efficacy and safety were assessed using the Psoriasis Area Severity Index (PASI) and the Quality of Life Index (QLI) questionnaires at different times throughout the 12-week study. The PASI was evaluated by the physician at the beginning (week 0) and end (week 12) of the study. The QLI was assessed by patients at weeks 0, 4, 8, and 12. The results indicate statistically significant (P < 0.05) improvements in PASI and QLI in the Mahonia-treated group, compared with the control group. The side effects reported were infrequent, < 1% and minor; the most frequent side effects were rash, a burning sensation when applying the cream, and clothing stain. These data indicate that Reliéva, a proprietary form of M. aquifolium, is effective and well tolerated in patients with mild to moderate psoriasis.

Fumaric Acid Esters:

Treatment of severe, recalcitrant, chronic plaque psoriasis with fumaric acid esters: a prospective study.

Abstract
BACKGROUND:
Fumaric acid esters (FAE) are used in Germany as a first-line systemic treatment for chronic plaque psoriasis, with proven efficacy and low toxicity. Their use in the U.K. is variable, and they remain unlicensed. Consequently, efficacy and safety data from U.K. patients is limited and their place in the psoriasis treatment armamentarium is unclear.
OBJECTIVES:
To examine the efficacy and safety of FAE in a prospective cohort of U.K. patients with severe, treatment-recalcitrant, chronic plaque psoriasis.
METHODS:
A single-centre, open, nonrandomized, prospective study was performed in a regional referral centre for patients with severe psoriasis. Outcomes were measured by the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), blood investigations and adverse events monitoring.
RESULTS:
Eighty patients were recruited. Fifty-nine per cent were taking a concomitant oral antipsoriatic agent; 20% achieved a PASI-50, 8% a PASI-75 and 4% a PASI-90 on intention-to-treat analysis at 3 months with an overall, statistically significant, reduction in PASI from 13.9 + or - 9.0 to 11.3 + or - 9.2 (P < 0.0001). At 3 months, lymphopenia was seen in 33% of the cohort with significantly lower counts in patients responsive to FAE (P = 0.008). In addition, by 3 months, 36% of concomitant antipsoriatic medication had been stopped and 25% of doses had been reduced without loss of disease control. Side-effects (most commonly diarrhoea, abdominal pain and flushing) were reported by 74% of patients resulting in cessation of FAE in 36%.
CONCLUSIONS:
FAE is a useful alternative treatment option in patients with severe, treatment-resistant, chronic plaque psoriasis and can allow dose reduction, and subsequent cessation, of other, potentially more toxic agents.

Fumaric acid esters for severe psoriasis: a retrospective review of 58 cases.

Abstract
BACKGROUND:
Fumaric acid esters (FAE) have been used to treat severe psoriasis in northern Europe for over 20 years. A recent systematic review has shown FAE to be an effective systemic treatment for severe psoriasis. However, FAE remain unlicensed in the U.K.
OBJECTIVES:
To present data relating to the efficacy and tolerability of FAE in severe psoriasis and report our experiences of FAE therapy at one U.K. centre.
METHODS:
Patients who had received FAE for severe psoriasis at one U.K. regional referral centre between June 1999 and October 2003 were identified from pharmacy records. Their records were analysed retrospectively.
RESULTS:
Fifty-eight patients (25 women, 33 men) were identified. Fifty-five (95%) of the 58 patients had previously used other systemic antipsoriatic therapies with over 70% previously using two or more agents. Thirty-two patients (55%) showed improvement in their psoriasis with 10 (17%) being rated as 'clear' or 'virtually clear' by the attending physician. No improvement was seen in 28% patients and 16% showed worsening of their disease. Adverse events were common and were reported in 66% patients. These mainly consisted of abdominal pain (61%), diarrhoea (55%), flushing (45%), nausea (21%) and malaise (15%). They led to discontinuation of treatment in 15 patients after a mean period of 4.7 months. Lymphocytopenia developed during treatment in 57% of patients, all of whom had had a baseline value within the normal range. In only one patient was this considered severe enough to warrant withdrawal of treatment.
CONCLUSIONS:
Our study has shown that FAE are an effective therapy in selected patients with severe psoriasis, even in those who have previously been intolerant of systemic therapy or where it has failed.

Sweet whey extract:

XP-828L in the treatment of mild to moderate psoriasis: randomized, double-blind, placebo-controlled study.

Abstract
BACKGROUND:
XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study.
OBJECTIVE:
To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis.
DESIGN:
XP-828L 5 g/d (group A, n=42) or placebo (group B, n=42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days.
RESULTS:
Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo (p less than 0.05). Considering the data of group A only, the PGA score improved from day 1 to day 56 (p less than 0.01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent (p less than 0.05).
CONCLUSION:
Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.

Pycnogenol:

Improvement in signs and symptoms in psoriasis patients with Pycnogenol® supplementation.

Abstract
AIM:
The aim of the study was the evaluation of supplementation with Pycnogenol®, French maritime pine bark extract (registered trademark of Horphag Research Ltd.) to improve the effects of the management of psoriasis and reduce the need for treatments.
METHODS:
Patients (age range 30-45) with moderate/severe plaque psoriasis were included in a 12-week registry study that did not interfere with 'standard management'. The minimum Psoriasis Area Severity Index (PASI) score at inclusion was 10. Subjects with 10-29% (grade 2) and 30-49% (grade 3) of involved area were included. Oxidative stress (plasma free radicals) was measured. Patient-reported measures included the Dermatology Life Quality Index (DLQI). The supplement was used at a dosage of 150 mg/day (50 mg three times daily).
RESULTS:
The two registry groups (standard management and standard management+supplementation) were comparable. Dropouts were due to logistical problems. Single PASI items were evaluated: a decrease in the affected body area in boths groups was observed. The decrease in affected areas was more pronounced in the Pycnogenol group in all body regions. The severity score (erythema, induration, desquamation) improved more significantly with Pycnogenol. Considering the water content of skin in all areas, the increase was higher with Pycnogenol. The quantity of exfoliating cells (score from -5 to +5) was significantly reduced in both groups, with a better action using Pycnogenol. Skin moisture improved with treatment in all subjects, with better effects using Pycnogenol. Using a modified (12 items) DLQI indicating how much psoriasis had affected the patient's life in the previous week, Pycnogenol-supplemented subjects performed better for each single parameter in comparison with standard management. Improvement in the treatment time (-32% in comparison with standard management) and costs (decreased on average 36.4% in comparison with standard management) were observed in the supplement group. A decrease in consumption of other drugs was observed with the supplement. Oxidative stress was significantly lower in the supplement group at 12 weeks.
CONCLUSION:
These results indicate the efficacy of Pycnogenol supplementation in improving control of the most common clinical aspects of psoriasis and in reducing oxidative stress. Further studies may indicate the possible systemic or local use of Pycnogenol and its role in controlling side effects and costs of standard management.

[Phoenicis]

Hey Soma, what's up? Have you tried any of those yet? Currently my strategy is - curcumin, resveratrol, indian gooseberry (also bcl-2 down regulator) and ECGC (for hair loss). The butyrate is part of the game too and I really like tazarotene since it is helping with the psoriais on my elbows and improving the skin on my face in terms of pore size and skin thickness.

 

My next approach is trying red (630 nm) and IR (850 nm) LED therapy for removing spider veins on the sides of my nose that were left behind after the psoriais disappeared. It also seems to be useful for scars, acne, photo-rejuvination, rosacea and so on. 

 

http://www.ecardiolo...ting_Diodes.pdf

 

Interesting info from that review potentially usefull in psoriasis:

 

"A series of recent studies have demonstrated the anti-inflammatory potential of LED. A study conducted in arachidonic acid-treated human gingival fibroblast suggests that 635 nm irradiation inhibits PGE 2 synthesis like COX inhib-itor and thus may be a useful antiinflammatory tool."

 

 

Resveratrol-

 

As mentioned for curcumin, the newest psoriasis stategies seem to focus on miR-21 and S100A9 inhibiting strategies. "Hundreds of increased or decreased genes have been described for psoriasis, but only a few of them—dozens—are supposed to be able to cause the disease," they say. "We have described two new genes/proteins that are known to show increased levels in psoriasis, and have now shown that they play a causal role in the disease."

 

The drugs seem to be quite expsensive and come with side effects, so I will continue my approach of using bcm-95 curcumin and LEF resveratrol. Not only do the two synergize for inflammation, but curcumin may help to overcome the attenuation of one of resveratrols mechanisms of action by preventing bcl-2 overexpression. Here is patent on a "pharmaceutical composition containing curcumin and resveratrol", obviously I do intend anyone to copy or use it, I'm posting it to show the interest of others in this topic.
 

Nicotine, selegiline and rasagiline all seem to upregulate bcl-2 and thus are in this way opposite to curcumin. The handy thing about this resveratrol and curcumin combo is that it also fights cancer as all of these studies seem to demonstrate.

 

Review - http://www.hindawi.c...na/2011/102431/

 

Studies -

 

1) Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expressionP.

   Liu,H. Liang,Q. Xia,P. Li,H. Kong,P. Lei,S. Wang,Z. Tu

 

"In this study, we demonstrated that the effect of resveratrol on apoptosis is due to inhibiting miR-21 regulation of BCL-2 expression."

 

2) Resveratrol repressed viability of U251 cells by miR-21 inhibiting of NF-κB pathway.

  Hongxiu Li, Zhijun Jia, Aimei Li, Gareth Jenkins, Xin Yang, Jun Hu, Wanhua Guo

 

ABSTRACT Resveratrol (RSV), a polyphenol, is known to play an important role in inhibiting proliferation and inducing apoptosis of glioma cells. The aim of this study was to explore the mechanism of RSV on U251 cells apoptosis. RSV showed a dose-dependent decrease in U251 cell viability. It could reduce IκB phosphorylation, nuclear P65 protein levels and NF-κB transcriptional activity, which suggested that signaling pathway are involved in RSV-induced apoptosis. In addition, RSV could inhibit miR-21 expression and down-regulation of miR-21 expression could suppress NF-κB activity. Interestingly, over-expression of miR-21 can reverse the effect of RSV on NF-κB activity and apoptosis in U251 cells. These results suggest that RSV can effectively induce apoptosis of U251 cells and modulation of miR-21 possibly contributes to this antitumor action.

 

3) Resveratrol inhibits prostate cancer metastasis by targeting microRNA-21

   Sandeep B. Sheth1, Sarvesh Jajoo1, Debashree Mukherjea1, Tejbeer Kaur1, Kelly Sheehan1, Leonard Rybak1, and Vickram Ramkumar1

 

"We conclude that resveratrol inhibits PC3-MM prostate cancer cell viability, invasion and migration by suppressing miR-21 expression via a growth factor/Akt sensitive pathway. We propose that oral administration of resveratrol inhibits prostate cancer growth and metastasis by abrogating a growth factor/Akt signaling pathway for induction of miR-21. These data support the use of resveratrol as a miR-21 inhibitor for the treatment of metastatic prostate cancer."

 

 

 

 

Edited by Phoenicis, 29 April 2014 - 10:35 PM.

[aribadabar]

Thank you everyone for the awesome ideas!

 

As to the whey idea - I have always been on the fence between treating whey as another diary product (which are known to be allergens , especially in dermatoses) and something different which is not (as) bad for skin conditions.

Do you think whey is safe to consume in this case? What about colostrum?

 

 

 

[Phoenicis]

tree, on 09 Apr 2014 - 02:16 AM, said:

[...]

Information is stored in the epigenome in several forms, among them are methyl and acetyl groups. HDAC inhibition forces the removal of methyl groups in favour for acetyl groups. This unlocks genes but some are locked for a good reason. If you take a lot of HDAC inhibitiors, it will start to unlock *all* locked genes. Which can cause cancer or other problems.

 

Just wanted to add that HDAC inhibitors are used for treating cancer, I haven't come across studies showing they cause cancer. It seems likelier to me that HDACi drugs would be of greater concern.

 

Here's one of the studies that came up as a result of search for 'HDAC inhibitors and cancer':

 

HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications.

Khan O¹, La Thangue NB.

Abstract

Reversible acetylation mediated by histone deacetylases (HDACs) influences a broad repertoire of physiological processes, many of which are aberrantly controlled in tumor cells. As HDAC inhibition prompts tumor cells to enter apoptosis, small-molecule HDAC inhibitors have been developed as a new class of mechanism-based anti-cancer agent, many of which have entered clinical trials. Although the clinical picture is evolving and the precise utility of HDAC inhibitors remains to be determined, it is noteworthy that certain tumor types undergo a favorable response, in particular hematological malignancies. Vorinostat and romidepsin have been approved for treating cutaneous T-cell lymphoma in patients with progressive, persistent or recurrent disease. Here, we discuss developments in our understanding of molecular events that underlie the anti-cancer effects of HDAC inhibitors and relate this information to the emerging clinical picture for the application of these inhibitors in the treatment of cancer.

 

The rest of the results, nothing negative...

 

• The role of histone deacetylases (HDACs) in human cancer

  www.sciencedirect.com/science/article/pii/S1574789107000026‎

  by S Ropero - ‎2007 - ‎Cited by 164 - ‎Related articles

  Class I and class II HDACs are sensitive to the classical HDAC inhibitor trichostatin A ... One possible explanation is that changes in DNA methylation also cause ...
• Histone deacetylase inhibitors in cancer treatment.

  www.ncbi.nlm.nih.gov/pubmed/11914636‎

  by DM Vigushin - ‎2002 - ‎Cited by 329 - ‎Related articles

  HDAC inhibition causes acetylated nuclear histones to accumulate in both tumor and normal tissues, providing a surrogate marker for the biological activity of ...
• Histone deacetylases and cancer: causes and therapies.

  www.ncbi.nlm.nih.gov/pubmed/11902574‎

  by P Marks - ‎2001 - ‎Cited by 1573 - ‎Related articles

  This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of ...
• Dietary phytochemicals, HDAC inhibition, and DNA damage ...

  www.clinicalepigeneticsjournal.com/content/3/1/4‎

  by P Rajendran - ‎2011 - ‎Cited by 36 - ‎Related articles

  Many HDACs overexpressed in cancer cells have been implicated in protecting such ... The latter review highlighted the ways in which HDAC inhibitors lead to ...
• Histone Deacetylase Inhibitors: A New Class of Potential ...

  clincancerres.aacrjournals.org/content/8/3/662.full‎

  by VM Richon - ‎2002 - ‎Cited by 130 - ‎Related articles

  HDAC2 inhibitors are members of a new class of agents that modulate the ... activity supports a model in which HDAC is the critical cellular target causing the ... or mutation in a variety of cancers, including those of both hematological and ...
• Histone deacetylases and cancer: causes and therapies ...

  www.nature.com › Journal home › Archive › Review‎

  by PA Marks - ‎2001 - ‎Cited by 1575 - ‎Related articles

  This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of ...
• Oncogene - Histone deacetylases and cancer - Nature

  www.nature.com › Journal home › Archive › Reviews‎

  by MA Glozak - ‎2007 - ‎Cited by 393 - ‎Related articles

  Treatment of many cancer cell types with any of several HDAC inhibitors causes the transcriptional upregulation of this antiproliferative gene. This is largely ...
• Figure 2 : Histone deacetylases and cancer: causes ... - Nature

  www.nature.com › Journal home › Archive › Review › Full text‎

  FIGURE 2 | Proposed mechanism of action of histone deacetylase inhibitors. From the following article: Histone deacetylases and cancer: causes and therapies.
• Histone Deacetylase Inhibitors in Cancer Therapy - Journal ...

  jco.ascopubs.org/content/27/32/5459.full.pdf‎

  by AA Lane - ‎2009 - ‎Cited by 433 - ‎Related articles

  10 Nov 2009 - tial of HDAC inhibitors in cancer treatment. His- ... HDACs causes the upregulation of the cell cycle gene p21WAF1/CIP1, blocking the Cyclin ...

 

[Phoenicis]

Today i decided to try taking 4 tablespoons of RS and 1 tablespoon of FOS on an empty stomach. I really like the effects, it makes me relaxed and very clear minded. Gives me a bit of gas too, but I am sort of used to that because I consume a lot of legumes. In my experience gas is usually a temporary thing that goes away after a few months. I'm interested to see where this leads.

 

Also please excuse the bad spelling/grammar in my last post. Read 'more likely' not 'likelier'.

Edited by Phoenicis, 01 May 2014 - 03:57 PM.

[Phoenicis]

Now that I think of it, people with psoriasis can be replace RS (resistant potato starch) with fructooligosaccharides (FOS) for a few reasons. 

 

1) people with psoriasis often find that potatoes (not sweet or purple) worsen their condition and thus may not want to take that RS.

 

2) FOS tastes sweet

 

3) FOS also yields butyrate:

-http://www.direct-ms...olon cancer.pdf

- http://onlinelibrary...003.01836.x/pdf  (see study table pg.316)

 

4) FOS is a better prebiotic -"With respect to impacts on microbiotal composition, both substrates were prebiotics, although RPS was less powerful than FOS. Both FOS and RPS increased the caecocolonic pools of LABP, Lactobacillus sp. and Gram-positive cocci, but FOS also affected facultative anaerobes and its effect was more intense and perceptible throughout the caecocolonic tract. " (Ibid)

 

 

http://aem.asm.org/c.../72/5/3593.full

 

"In conclusion, several mechanisms may contribute to the butyrogenic effects of dietary substrates such as FOS and starch. First, active fermentation tends to decrease the pH of the colonic lumen (6). This may have the effect of reducing competition for carbohydrate substrates from nonbutyrogenic species such asBacteroides when the pH is decreased from 6.7 to 5.7, as suggested by a recent study in vitro (44). Butyrate-producing bacteria that are able to directly utilize FOS and starch (13) therefore may be expected to compete better for these substrates and to contribute to increased butyrate production at the lower pH (44). Second, the current data demonstrate two potential indirect mechanisms that involve metabolic cross-feeding. The importance of specific cross-feeding in vivo via lactate needs to be assessed further by determining the rate of lactate production and utilization in the complete ecosystem. This may depend partly on the abundances of lactate utilizers in different individuals. In a wider context, cross-feeding of polysaccharide breakdown products released by bifidobacteria has the potential to stimulate butyrate production regardless of the ability of butyrate producers to utilize lactate.”

 

The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats.

 

http://www.ncbi.nlm....pubmed/12514261

Abstract

Fructooligosaccharides (FOS) increase the growth of lactic acid bacteria (LAB) and promote butyrate and lactate production. Because of these properties, FOS may benefit intestinal inflammation. The purpose of this study was to investigate the effect of FOS on colitis in rats and determine which factors are involved. Groups of rats with intracolonic trinitrobenzene sulfonic acid (TNBS)-induced colitis received intragastric infusions of 9 g/L NaCl, 1 g/d FOS or 10(11) colony-forming units (cfu)/d LAB (Experiment 1), or intracolonic infusions of 9 g/L NaCl, butyrate, lactate or butyrate + lactate with or without 10(9.5) cfu/d LAB (Experiment 2). Each infusion was administered twice daily for 14 d. Intragastric FOS reduced the gross score for inflammation (P < 0.001), myeloperoxidase (MPO) activity (P < 0.001) and pH (P < 0.001), and increased lactate (P = 0.02) and butyrate concentrations (P < 0.001) as well as LAB counts in the cecum (P < 0.01). Intragastric LAB (10(11) cfu/d) had the same beneficial effects as FOS and modified the cecal composition similarly. High doses of intracolonic butyrate and lactate reduced the indices of inflammation (P < 0.001), whereas administration of the lower concentrations found in the colon tended to decrease (P < 0.1) the gross score for inflammation and MPO activity. Addition of LAB (10(9.5) cfu/d) to the organic acids was necessary to reproduce the significant FOS-induced effects on these variables. Thus, under the experimental conditions used, FOS reduced intestinal inflammatory activity mainly by increasing LAB counts in the intestine.

 

Prolonged intake of fructo-oligosaccharides induces a short-term elevation of lactic acid-producing bacteria and a persistent increase in cecal butyrate in rats.

 

http://www.ncbi.nlm....pubmed/10573555

 

Abstract

While the prebiotic effects of fructo-oligosaccharides (FOS), short-chain polymers of fructose, have been thoroughly described after 2-3 wk of ingestion, effects after intake for several months are unknown. We tested the hypothesis that these effects would differ after ingestion for short and long periods in rats. Rats were fed a basal low-fiber diet (Basal) or the same diet containing 9 g/100 g of FOS for 2, 8 or 27 wk, and cecal contents were collected at the end of each time period. Cecal short-chain fatty acid concentration was higher in rats fed FOS than in those fed Basal, and this effect persisted over time: 83.8 +/- 4.1 vs. 62.4 +/- 6.5 micromol/g at 2 wk and 103.5 +/- 5.8 vs. 73.2 +/- 7.4 micromol/g at 27 wk (P < 0.05). The molar butyrate ratio was higher in rats fed FOS regardless of the time period (14.8 +/- 0.6% vs. 6.7 +/- 1.1% at 27 wk, P < 0.05). Lactate concentration in rats fed FOS was elevated after 2 wk and then decreased: 63.5 +/- 21.6 micromol/g at 2 wk vs. 8.8 +/- 3.3 micromol/g at 8 wk (P < 0.05). After 2 wk, FOS increased the concentrations of total lactic acid-producing bacteria, and Lactobacillus sp. (P < 0.05), without modifying total anaerobes. However, most of these effects were abolished after 8 and 27 wk of FOS consumption. In the long term, the FOS-induced increase in intestinal lactic acid-producing bacteria was lost, but the butyrogenic properties of FOS were maintained.

 

Prebiotic short chain fructooligosaccharides increase butyrate but not short chain fatty acid receptor or transporter mRNA in an intestinal failure piglet model

 

http://www.fasebj.or...Abstracts/867.6

 

"This study shows that scFOS increases butyrate in a pediatric IF model, but that SCFA receptor and transporter mRNA levels are influenced by other factors."

 

 

Edited by Phoenicis, 02 May 2014 - 12:19 AM.

[Phoenicis]

Some new updates on nutrition -

 

Neu5Gc, IGF-1, VEGF and Alpha Gal: these require further study!

 

Mild to Moderate Psoriasis, Third Edition  John Y. M. Koo, Ethan C. Levin, Argentina Leon and Jashin J. Wu (22 Apr 2014)

 

 "One potential proinflammitory compound found in red meat is a monosaccharide known as Neu5Gc. Neu5Gc accumulates in tissues after excess consumption of meat and dairy and is thought to be immunogenic [33, 34]. When meat is consumed regularly, it may lead to low levels of chronic inflammation that may increase the risk for autoimmune disease and cancer [33, 34]. Psoriasis patients are at increased baseline risk for some malignancies, including nonmelanoma skin cancers, lymphoma, and esophageal cancer, and this risk increases with more severe disease. [35]. Thus, by reducing meat intake, psoriasis patients may decrease systemic inflammation, improve psoriasis, and possibly decrease cancer risk. However the role of Neu5Gc in psoriasis has not been specifically examined."

 

[...]

 

"In addition to its proinflammatory effects, excess consumption of animal protein may enhance angiogenisis, a pathological component of both psoriais and cancer [36]. Increased angiogenisis in psoriatic plaques is needed for keratinocyte hyperproliferation and recruitment of lymphocytes, neutophils, and dendritic cells. The angiogenic mediators insulin-like growth factor 1 (IGF-1) [37, 38-40] and vascular endothelial growth factor (VEGF) [40] are shown to increase after high protein meals. IGF-1 facilitates angiogenisis in several ways, including increasing the sensitivity of endothelial cells to VEGF [39, 40]. Animal proteins have a unique ability to raise serum IGF-1 levels through upregulated hepatic synthesis and enhanced glucose-dependant insulin secretion [41]. Epidemiologic studies show an association between animal protein consumption and increased IGF-1 levels [42-44]."

 

 

Neu5Gc is addressed in this video:

 

 

Sources Cited

McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med. 2002 Feb;8(1):71-5. 

Varki A. Colloquium paper: uniquely human evolution of sialic acid genetics and biology. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8939-46. 

Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12045-50. 

Padler-Karavani V, Yu H, Cao H, Chokhawala H, Karp F, Varki N, Chen X, Varki A. Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology. 2008 Oct;18(10):818-30. 

Varki, A.: Evolutionary Perspectives on the Origin of Diseases IN, Current Trends in Sciences (Invited Book Chapter), Ed. N. Mukunda. Indian Academy of Sciences, Bangalore, India, pp. 395-402, 2009. 

 

 

Other compounds like AlphaGal may be interesting as well!

 

 

Sources Cited

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The Video Referenced:

 

 

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Edited by Phoenicis, 18 May 2014 - 03:26 PM.

[copiacorpus]

I´m trying Vit E

Tocopherol

from wheat germ oil.

Edited by copiacorpus, 21 November 2017 - 01:34 AM.

[pamojja]

Being on comprehensive supplementation ala Linus Paulings therapy for an other condition for 9 years (basically all vitamins, most minerals and some amino-acids), and only once I exceeded a daily dose of 24.000 IUs preformed vitamin A my infrequent psoriasis outbreaks ceased completely.