HAN Psor -->FoxP3 & TREGs --ERV's -->Human Endogenous Retrovirus K dUTPase -->PSRO GOOD:? -- TWEAK - TNFSF12 -->TNFα & TRAIL Proteins -- CD11c(+) -- More JXR Busy Bee PANCAN +++++++

[randall]

hi


FoxP3 and TREGs and Chinese Han's with psor?

A good psor test bed?

http://en.wikipedia.org/wiki/Han_Chinese
Han Chinese or Han People (simplified Chinese: 汉族 or 汉人; traditional
Chinese: 漢族 or 漢人; pinyin: hànzú or hànrén) are an ethnic group native
to China and are the largest single ethnic group in the world.

Han Chinese constitute about 92% of the population of the People's
Republic of China (mainland China), 98% of the population of the
Republic of China (Taiwan), 74% of the population of Singapore, and
about 20% of the entire global human population, making it the largest
ethnic group in the world.
<snip>

Say more!

look at it:

http://www.ncbi.nlm.nih.gov/pubmed/22435141
Indian J Biochem Biophys. 2012 Feb;49(1):25-35.
An association study of single nucleotide polymorphisms of the FOXP3
intron-1 and the risk of Psoriasis vulgaris.

Song QH, Shen Z, Xing XJ, Yin R, Wu YZ, You Y, Guo H, Chen L, Hao F,
Bai Y.

Source
Department of Dermatology, Southwest Hospital, College of Basic
Medical Science, Third Military Medical University, Chongqing 400038,
China.

Abstract
Psoriasis vulgaris (PV) is a common autoimmune disease that involves
the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key
transcription factor in the development and function of CD4+CD25+
regulatory T cells. Previous studies have demonstrated a genetic
association between the FOXP3 gene and some autoimmune diseases. To
elucidate the association between the FOXP3 gene and the risk of PV,
408 patients diagnosed with PV and 363 age and sex-matched healthy
controls from a cohort of the Chinese majority Han population were
recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547,
rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the
polymerase chain reaction and ligase detection reaction. The major
allele of three single nucleotide polymorphisms (SNPs - rs2232365 A,
rs3761547 A and rs3761549 C) were associated with an increased risk of
PV in a clinical subgroup of female patients, who were less than 40
yrs of age, had a family history of the disease and did not have
disease complications (p < 0.05 for all parameters). The haplotype was
structured between rs3761547 and rs3761549. An increased risk of PV
was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188;
95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288;
95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic
effect was found among the three SNPs. Subjects with the rs2232365AA-
rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR
= 2.90; 95% CI = 1.05-7.97). No correlation was found between
rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms
appear to contribute to the risk of psoriasis among the Chinese
majority Han population. These findings may aid in our understanding
of the pathogenesis of psoriasis.

PMID: 22435141

Y Bai has 1562 hits -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bai%20Y%22%5BAuthor%5D

But ONLY two of 1562 have psoria*
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bai%20Y%22%5BAuthor%5D%20psoria*

Bai's #2 of 1562 was posted:
Tues, Mar 1 2011 12:53 pm
Subject: Microbiota & Your- LIVER & BRAIN -->P450 -- Anne BOWCOCK NPF
- Abstractions Galore -> RANKL - shRNA -siRNA - LL37 - IBD or SKIN? -
LXR's -PsA -Mer cola -Pharma Science as BS? -Iodine leptin & Psor -AP1
- JUN - mAbs -TNF -Zonulin -FLG & LOR - Z - +
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+21349840+&start=0&


Bai has twice as many Foxp3's as psoriasis abstracts
"Bai Y"[Author] foxp3
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bai%20Y%22%5BAuthor%5D%20foxp3

367 hits: foxp3 -- p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=foxp3&start=0&

http://en.wikipedia.org/wiki/Foxp3
FOXP3 (forkhead box P3) is a protein involved in immune system
responses. A member of the FOX protein family, FOXP3 appears to
function as a master regulator in the development and function of
regulatory T cells.[1]

While the precise control mechanism has not yet been established, FOX
proteins belong to the forkhead/winged-helix family of transcriptional
regulators and are presumed to exert control via similar DNA binding
interactions during transcription.
<snip>

FoxP3 makes TREGs (Th2 skew if to MANY T regulatory cells)
http://en.wikipedia.org/wiki/Regulatory_T_cells
Regulatory T cells (Treg), sometimes known as suppressor T cells, are
a subpopulation of T cells which downregulates the immune system,
maintains tolerance to self-antigens, and downregulates autoimmune
disease. Mouse models have suggested that modulation of Tregs can
treat autoimmune disease and cancer, and facilitate organ
transplantation.
<snip the TREGs... or raise more TREGs to lower psoriasis>



++++++++++++++++++++++++++++++++++++++++++++++++++

A good virus for PSORiASiS?


No way????

But it says... protective.... and it's.. From St. Louis Anne via UCSF
and Liao?

OK while i'm not sure about Liao!.... I luv runX Anne B.

BOWCOCk alert:


3 2 1 ---->>>>>>>>>>>>>>>>>><<<<<<<<<<<<<---------

http://www.ncbi.nlm.nih.gov/pubmed/22437317
J Invest Dermatol. 2012 Mar 22. doi: 10.1038/jid.2012.69.
Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on
Psoriasis Susceptibility.

Lai OY, Chen H, Michaud HA, Hayashi G, Kuebler PJ, Hultman GK, Ariza
ME, Williams MV, Batista MD, Nixon DF, Foerster J, Bowcock AM, Liao W.

Source
Department of Dermatology, University of California, San Francisco,
San Francisco, California, USA.

Abstract
Previous genetic and functional studies have implicated the human
endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1
locus in the major histocompatibility complex region as a candidate
psoriasis gene. Here, we describe a variant discovery and case-control
association study of HERV-K dUTPase variants in 708 psoriasis cases
and 349 healthy controls. Five common HERV-K dUTPase variants were
found to be highly associated with psoriasis, with the strongest
association occurring at the missense single-nucleotide polymorphism
(SNP) rs3134774 (K158R, P=3.28 × 10(-15), odds ratio =2.36 (95%
confidence interval: 1.91-2.92)). After adjusting the association of
the HERV-K dUTPase variants for the potential confounding effects of
HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and
rs3134774 remained significantly associated. Haplotype analysis
revealed that HERV-K haplotypes containing the non-risk alleles for
rs3134774 and rs9264082 significantly reduced the risk of psoriasis.
Functional testing showed higher antibody responses against
recombinant HERV-K dUTPase in psoriasis patients compared with
controls (P<0.05), as well as higher T-cell responses against a single
HERV-K dUTPase peptide (P<0.05). Our data support an independent role
for the HERV-K dUTPase on psoriasis susceptibility, and suggest the
need for additional studies to clarify the role of this dUTPase in the
pathogenesis of psoriasis.Journal of Investigative Dermatology advance
online publication, 22 March 2012; doi:10.1038/jid.2012.69.

PMID: 22437317

ERV's (Endogenous Retrovirus) are bad for MS, ALS and cancer and
autoimmune conditions? But not psoriasis?


This is gonna be so... so, so i DON'T KNOW... LOL

BUT,

Wow.. i should know Liao.

Liao knows PSOR!

460 hits -"Liao W"[Author]
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liao%20W%22%5BAuthor%5D

14 of 460(?) -- for Liao have keyword: psoria*
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liao%20W%22%5BAuthor%5D%20psoria*

#2 of 14 [ PMID: 22185198] was posted
PMID: 22185198 - December 23, 2011 --
Association analysis identifies ZNF750 regulatory variants in
psoriasis.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+22185198&start=0&

And wilson Liao does Psor day in the BAY City of SF?

yep:

http://www.dermatology.ucsf.edu/faculty_staff/StaffBios/LiaoWilson.aspx
Wilson Liao, MD
Assistant Professor of Clinical Dermatology
Department of Dermatology

Contact Information
Psoriasis Day Care Center
515 Spruce Street, San Francisco, CA 94143-1212

Training
MD: Harvard Medical School
Dermatology Residency: University of California, San Francisco
Dr. Liao specializes in the care of patients with psoriasis and photo-
responsive disorders. He is interested in bringing cutting-edge
research technologies into the dermatology clinic. Dr. Liao is
involved in a number of research studies for psoriasis and skin cancer
and welcomes patient inquiries on study participation.
<snip>

He looks YOUNGer then 480 abstracts unless he did some in his sleep?
LoL
http://www.ucsfhealth.org/wilson.liao
<snip>

Let's find his virus:

358 hits for: herv k- pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=herv%20k

341 with retrovirus added in:
http://www.ncbi.nlm.nih.gov/pubmed?term=retrovirus%20herv%20k

4 of 341 have : psoria* -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=retrovirus%20herv%20k%20psoria*

#2 of 4: PMID: 21776007 : was posted in the dorking out in the Gi
tract thread:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+21776007+&start=0&
<snip>

#3 of 4 : PMID: 16029331 has been posted twice:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+16029331+&start=0&

4 of 4 PMID: 15654959 also posted twice p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+15654959+&start=0&

redux of #4of4

http://www.ncbi.nlm.nih.gov/pubmed/15654959
J Invest Dermatol. 2005 Jan;124(1):99-102.
Haplotype sharing analysis identifies a retroviral dUTPase as
candidate susceptibility gene for psoriasis.

Foerster J, Nolte I, Junge J, Bruinenberg M, Schweiger S, Spaar K, van
der Steege G, Ehlert C, Mulder M, Kalscheuer V, Blumenthal-Barby E,
Winter J, Seeman P, Ständer M, Sterry W, Te Meerman G.

Source
Klinik für Dermatologie, Charité, Schumannstr., Berlin, Germany.
john.f...@charite.de

Abstract
The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to
reside within a region around human leukocyte antigen-C spanning 250
kb, termed risk haplotype (RH) 1/2. By re-analyzing a published data
set with a previously developed method, the haplotype sharing
statistic, we confirm localization of PSORS1 to the RH1 region and
refine its location to marker M6S168. We replicate this result in an
independent patient sample. The target region harbors fragments of a
human endogenous retrovirus K (HERV-K) endogenous retrovirus. Two
single-nucleotide polymorphisms with alleles differing between high-
and low-risk haplotypes are located within the HERV-K dUTPase. One of
these encodes a predicted non-conserved Glu-Arg exchange. The HERV-K
dUTPase is expressed in peripheral blood and in normal as well as
lesional psoriatic skin. Our results indicate that an endogenous
retroviral dUTPase constitutes a candidate gene for the PSORS1
mutation.

PMID: 15654959
Free full text


&&&&&&&&&&&&&&&&&&&&&&

http://en.wikipedia.org/wiki/Endogenous_retrovirus
Endogenous retroviruses (ERVs) are sequences in the genome thought to
be derived from ancient viral infections of germ cells in humans,
mammals and other vertebrates; as such their proviruses are passed on
to the next generation and now remain in the genome.

Hypothesis of origin
Endogenous retroviruses may be a variant of a retrovirus which became
permanently integrated with its host and is inherited from generation
to generation as part of the genome of the host.
Retroviruses are single-stranded RNA viruses that reverse-transcribe
their RNA into DNA for integration into the host's genome. Most
retroviruses (such as HIV-1) infect somatic cells, but in very rare
cases, it is thought that exogenous retroviruses have infected
germline cells (cells that make eggs and sperm) allowing integrated
retroviral genetic sequences to be passed on to subsequent progeny,
thereby becoming 'endogenous'. Endogenous retroviruses have persisted
in the genome of their hosts for thousands of years. However, they are
generally only infectious for a short time after integration as they
acquire many inactivating mutations during host DNA replication. They
can also be partially excised from the genome by a process known as
recombinational deletion. They are thought to play a key role in
evolution.[1] Some human ERVs have been implicated in ALS[2], certain
autoimmune diseases, and cancers.[3][4]

Human endogenous retroviruses
Human endogenous retroviruses (HERVs) are suspected of involvement in
some autoimmune diseases, in particular with multiple sclerosis. In
this disease, there appears to be a specially associated member of the
family of human endogenous retrovirus W known as "MS-associated
retrovirus" (MSRV).[5] [6]

Thousands of endogenous retroviruses exist in human DNA. HERVs make up
98,000 elements and fragments—nearly 8%—of the human genome.[7]
According to a study published in 2005, no HERVs capable of
replication had been identified; all appeared to be defective,
containing major deletions or nonsense mutations. This is because most
HERVs are merely traces of original viruses, having first integrated
millions of years ago. However, one family of viruses has been active
since the divergence of humans and chimpanzees. This family, termed
HERV-K (HML2), makes up less than 1% of HERV elements but is one of
the most studied. There are indications it has even been active in the
past few hundred thousand years, e.g., some human individuals carry
more copies of the virus family than others [8]. Traditionally, age
estimates of HERVs are performed by comparing the 5' and 3' LTR of a
HERV; however, this method is only relevant for full-length HERVs. A
recent method called cross-sectional dating [9] uses variations within
a single LTR to estimate the ages of HERV insertions. This method is
more precise in estimating HERV ages and can be used for any HERV
insertions. Cross-sectional dating has been used to suggest that two
members of HERV-K(HML2), HERV-K106, and HERV-K116 were active in the
last 800,000 years and that HERV-K106 may have infected modern humans
150,000 years ago [10]. However, the absence of known infectious
members of the HERV-K(HML2) family, and the lack of elements with a
full coding potential within the published human genome sequence,
suggests to some that the family is less likely to be active at
present.

In 2004 it was reported that antibodies to HERVs were found in greater
frequency in the sera of people with schizophrenia. Additionally, the
cerebrospinal fluid of people with recent onset schizophrenia
contained levels of a retroviral marker, reverse transcriptase, four
times higher than control subjects.[11] Researchers continue to look
at a possible link between HERVs and schizophrenia, with the
additional possibility of a triggering infection inducing
schizophrenia.[12]

In 2006, researchers led by Thierry Heidmann at the Institut Gustave
Roussy in Villejuif, France, were able to recreate a HERV, which they
dubbed Phoenix.[13][14]

In 2007, a group led by Doug Nixon and Keith Garrison at the
University of California, San Francisco, and by Mario Ostrowski and
Brad Jones at the University of Toronto, published a study providing
evidence for T cell immune responses against HERVs in HIV-infected
individuals.[15] The group hypothesized that HIV induces HERV
expression in HIV infected cells, and that a vaccine targeting HERV
antigens could therefore specifically eliminate HIV infected cells.
The potential advantage of this novel approach is that, by using HERV
antigens as surrogate markers of HIV infected cells, it could
circumvent the difficulty inherent in directly targeting notoriously
diverse and fast-mutating HIV antigens.
<snip>

http://upload.wikimedia.org/wikipedia/commons/a/a9/Classes_of_ERVs.jpg

Did erv's kill Lou Gehrig ALS?

http://en.wikipedia.org/wiki/ALS
Amyotrophic lateral sclerosis (ALS), also referred to as Lou Gehrig's
disease
<snip>


^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

http://www.ncbi.nlm.nih.gov/pubmed/22438963
PLoS One. 2012;7(3):e33609. Epub 2012 Mar 16.
TWEAK Affects Keratinocyte G2/M Growth Arrest and Induces Apoptosis
through the Translocation of the AIF Protein to the Nucleus.

Sabour Alaoui S, Dessirier V, de Araujo E, Alexaki VI, Pelekanou V,
Lkhider M, Stathopoulos EN, Castanas E, Bagot M, Bensussan A, Tsapis
A.

Source
Inserm, U976, Paris, France.

Abstract
The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds
to the fibroblast growth factor-inducible 14 receptor (FN14,
TNFRSF12A) on the cell membrane and induces multiple biological
responses, such as proliferation, migration, differentiation,
angiogenesis and apoptosis. Previous reports show that TWEAK, which
does not contain a death domain in its cytoplasmic tail, induces the
apoptosis of tumor cell lines through the induction of TNFα secretion.
TWEAK induces apoptosis in human keratinocytes. Our experiments
clearly demonstrate that TWEAK does not induce the secretion of TNFα
or TRAIL proteins. The use of specific inhibitors and the absence of
procaspase-3 cleavage suggest that the apoptosis of keratinocytes
follows a caspase- and cathepsin B-independent pathway. Further
investigation showed that TWEAK induces a decrease in the
mitochondrial membrane potential of keratinocytes. Confocal microscopy
showed that TWEAK induces the cleavage and the translocation of
apoptosis inducing factor (AIF) from the mitochondria to the nucleus,
thus initiating caspase-independent apoptosis. Moreover, TWEAK induces
FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and
cyclinB1 degradation, resulting in the arrest of cell growth at the G2/
M phase. Finally, we report that TWEAK and FN14 are normally expressed
in the basal layer of the physiological epidermis and are greatly
enhanced in benign (psoriasis) and malignant (squamous cell carcinoma)
skin pathologies that are characterized by an inflammatory component.
TWEAK might play an essential role in skin homeostasis and pathology.

PMID: 22438963


http://en.wikipedia.org/wiki/TNFSF12
Symbols TNFSF12; APO3L; DR3LG; TWEAK
Tumor necrosis factor ligand superfamily member 12 is a protein that
in humans is encoded by the TNFSF12 gene.[1][2][3]
The protein encoded by this gene is a cytokine that belongs to the
tumor necrosis factor (TNF) ligand family. This protein is a ligand
for the FN14/TWEAKR receptor. This cytokine has overlapping signaling
functions with TNF, but displays a much wider tissue distribution.
This cytokine can induce apoptosis via multiple pathways of cell death
in a cell type-specific manner. This cytokine is also found to promote
proliferation and migration of endothelial cells, and thus acts as a
regulator of angiogenesis.
<snip>


44 tweak hits - p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=tweak&start=0&scoring=d&

But most are weak and not the tweak we seek.

And ONLY one of 44 has TNFSF12 thusly being REAL tweaks:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=tweak+TNFSF12&start=0&

#1 of 1
Wed, Jan 5 2011 12:19 am
Subject: Dr. Mark Hyman - Dr.Ron Drucker - JXR 2011--> Cocktail time?
- Psor Abstracts -+++
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/c8a87930b7236558


#2 of 45 (TWEAK hits P NG)
Many tweak hits:
super TWEAK:
Wed, Aug 16 2006 2:31 pm
Subject: Re: sPecial P News
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/bd6fe0354d4192b0

----

6 hits : psoria* TNFSF12- pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=psoria*%20TNFSF12

#1 is above
#2 is PMID: 21797919 and not posted:
http://www.ncbi.nlm.nih.gov/pubmed/21797919
J Cutan Pathol. 2011 Oct;38(10):780-9. doi: 10.1111/j.
1600-0560.2011.01762.x. Epub 2011 Jul 29.
Expression of TWEAK in normal human skin, dermatitis and epidermal
neoplasms: association with proliferation and differentiation of
keratinocytes.
[...]TWEAK was robustly expressed in the epidermis of healthy skin and
decreased in inflammatory conditions, both in the context of epidermal
hyperplasia and atrophy. Decreased TWEAK immunoreactivity was
regularly observed in common warts, actinic keratosis and Bowen's
disease, particularly in areas of marked proliferation as evidenced by
PCNA-positive nuclei. In squamous cell carcinoma, expression of TWEAK
ranged from strong to completely absent, and it mostly corresponded
with the expression of cytokeratin-10. TWEAK was absent in
keratoacanthoma and basal cell carcinoma.
CONCLUSIONS:
TWEAK is a constitutively expressed epidermal protein whose
downregulation might be an early indicator of disturbed
differentiation or pathologic proliferation of keratinocytes that
accompany inflammatory and neoplastic skin diseases.
<snip>

#3 of 6 has not been posted:
http://www.ncbi.nlm.nih.gov/pubmed/21762126

[...] In conclusion, we show that serum levels of TWEAK were elevated
in patients with acute stage HSP. TWEAK may act as a regulator of
nuclear factor-κB (NF-κB) activation and chemokine production in human
dermal microvascular endothelial cells, thus promoting leucocyte
migration in cutaneous vasculitis.
pmid: 21762126
<snip>

#4 of 6
http://www.ncbi.nlm.nih.gov/pubmed/21211655
TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the
induction of keratinocyte apoptosis.
Zimmermann M, Koreck A, Meyer N, Basinski T, Meiler F, Simone B,
Woehrl S, Moritz K, Eiwegger T, Schmid-Grendelmeier P, Kemeny L, Akdis
CA.
J Allergy Clin Immunol. 2011 Jan;127(1):200-7, 207.e1-10.

#5 of 6 was posted to the p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+21190865&start=0&scoring=d&

6 of 6 was posted to the p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+19147618+&start=0&scoring=d&


REDUX:
http://www.ncbi.nlm.nih.gov/pubmed/19147618
Ann Rheum Dis. 2010 Jan;69(1):301-4.
TWEAK and its receptor Fn14 in the synovium of patients with
rheumatoid arthritis compared to psoriatic arthritis and its response
to tumour necrosis factor blockade.

van Kuijk AW, Wijbrandts CA, Vinkenoog M, Zheng TS, Reedquist KA, Tak
PP.

Source
Division of Clinical Immunology and Rheumatology, Academic Medical
Center/University of Amsterdam, NL-1105 AZ Amsterdam, The Netherlands.

Abstract
OBJECTIVE:
To investigate the expression of tumour necrosis factor (TNF)-like
weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth
factor inducible 14 (Fn14) in the inflamed synovium of patients with
arthritis, as TWEAK blockade has been observed to have a beneficial
effect in an animal model of rheumatoid arthritis (RA).

METHODS:
Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate-
naive patients with RA as well as 13 patients with RA and 16 patients
with psoriatic arthritis (PsA) who were matched for treatment and
disease duration. Serial ST samples were obtained from a separate
cohort of 13 patients with RA before and after infliximab treatment.
TWEAK and Fn14 expression was evaluated by immunohistochemistry and
digital image analysis.

RESULTS:
TWEAK and Fn14 were clearly expressed in ST of patients with RA and
PsA. TWEAK expression was significantly higher in RA (sub)lining
samples compared to PsA (p = 0.005 and p = 0.014, respectively), but
Fn14 expression was comparable. Double immunofluorescence showed TWEAK
and Fn14 expression on fibroblast-like synoviocytes and macrophages,
but not T cells. Of interest, persistent TWEAK and Fn14 expression was
found after anti-TNF therapy.

CONCLUSIONS:
TWEAK and Fn14 are abundantly expressed in the inflamed synovium of
patients with RA and PsA. This raises the possibility that blocking
TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory
arthritis.

PMID: 19147618
Free PMC Article
PMID: 21211655


^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^


http://www.ncbi.nlm.nih.gov/pubmed/22438166
Arch Dermatol Res. 2012 Mar 22.
Rise in dermal CD11c(+) dendritic cells associates with early-stage
development of psoriatic lesions.

Teunissen MB, Zheng L, de Groot M, de Rie MA, Fine JS, Chen SC.

Source
Department of Dermatology, Academic Medical Center, University of
Amsterdam, M3-106, P.O. Box 22700, 1100 DE, Amsterdam, The
Netherlands, m.b.te...@amc.uva.nl.

Abstract
There is limited information available regarding the phenotype and
function of leukocytes involved in the earliest stages of psoriatic
lesion development. In this study, we examined the presence of
different types of leukocytes in psoriatic point lesions collected at
three 1-week interval time points from a recent and simultaneously
formed group of point lesions. The cells were quantified and compared
with K16 expression and epidermal thickness, both typically increased
in this disease and considered as hallmarks. We found a significant
correlation between K16(+) cell increment and the increase in
epidermal thickness in the timeframe of 14 days. The change in CD3(+),
CD4(+), and CD8(+) T-cell numbers in the dermis showed a significant
association with these two features from d7 to d14, whereas in the
epidermis only CD8(+) T cells demonstrated a significant correlation.
Remarkably, the relationship between T cells and disease progression
was preceded by a significant correlation of CD11c(+) dendritic cells
(DCs) with K16 expression and epidermal thickness from baseline
onwards. Interestingly, there was also a numeric correlation of
CD11c(+) DCs with the CD3(+) T-cell shifts from d7 to d14. A
significant correlation was also found between dermal CD14(+) cells
and K16 expression from d7 to d14. BDCA-2(+) plasmacytoid DCs were
absent in non-lesional skin, but found at low numbers in most lesions.
The change in plasmacytoid DC or neutrophil numbers did not correlate
with lesion development. In conclusion, our study suggests a relevant
role for T cells, and in particular dermal CD11c(+) DCs, in the
earliest stage of psoriatic lesion development.

PMID: 22438166

210 hits: CD11* + psoria* - pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=psoria*%20CD11*

#1 of 210 is ABOVE:

48 of 210 have CD11c
http://www.ncbi.nlm.nih.gov/pubmed?term=psoria*%20CD11c

-----

http://www.uniprot.org/uniprot/P20702
P20702 (ITAX_HUMAN)
Integrin alpha-X
Alternative name(s):
CD11 antigen-like family member C
Leu M5
Leukocyte adhesion glycoprotein p150,95 alpha chain
Leukocyte adhesion receptor p150,95
CD_antigen=CD11c
<snip>

CD11c(+) --> 75 hits --> P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=CD11c(%2B)+&start=0&

http://en.wikipedia.org/wiki/CD11c
Symbols ITGAX; CD11C; SLEB6
CD11c, also known as Integrin, alpha X (complement component 3
receptor 4 subunit) (ITGAX), is a human gene.[1]
This gene encodes the integrin alpha X chain protein. Integrins are
heterodimeric integral membrane proteins composed of an alpha chain
and a beta chain. This protein combines with the beta 2 chain (ITGB2)
to form a leukocyte-specific integrin referred to as inactivated-C3b
(iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap
the properties of the alpha M beta 2 integrin in the adherence of
neutrophils and monocytes to stimulated endothelium cells, and in the
phagocytosis of complement coated particles.[1]
CD11c is a type I transmembrane protein found at high levels on most
human dendritic cells, but also on monocytes, macrophages,
neutrophils, and some B cells that induces cellular activation and
helps trigger neutrophil respiratory burst; expressed in hairy cell
leukemias, acute nonlymphocytic leukemias, and some B-cell chronic
lymphocytic leukemias.
<snip>

http://en.wikipedia.org/wiki/Integrin
Integrins are receptors that mediate attachment between a cell and the
tissues surrounding it, which may be other cells or the ECM. They also
play a role in cell signaling and thereby regulate cellular shape,
motility, and the cell cycle.
<snip>

248 hits: LPS + CD11c(+)- pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=CD11c(%2B)%20LPS

51 hits: CD11c(+) + Th17
http://www.ncbi.nlm.nih.gov/pubmed?term=CD11c(%2B)%20Th17

2 of 51 have LPS:

2 hits - CD11c(+) Th17 LPS- pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=CD11c(%2B)%20Th17%20LPS

#1
http://www.ncbi.nlm.nih.gov/pubmed/21471450
[...] pmid: 21471450

#2 (get DhA in to you to stop inflammation)
http://www.ncbi.nlm.nih.gov/pubmed/20122166
[...] pmid: 20122166

------

151 hits - CD11c(+) Fc receptor -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=CD11c(%2B)%20Fc%20receptor

======================


And to follow up on my recent--->> PANCAN threads:<---

As JxR got my pancan juices going via in vino veritas and the birds
and bees...

And.... the BUZZ is... busy bee's find the stuff to make honey...

Mon, Mar 19 2012 4:01 pm
Subject: Pancan - Cancer--> Resveratrol, Genistein and Baicalein--
Atad5 & Psors2 --> Anti-ROS Works!... do YOU?
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/ce5e2926d88aee85

All--> 64 pancan hits - p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=pancan&start=0&
chrono order 59 hits:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=pancan&start=0&scoring=d&


Black cohosh is good for hot flashes and menopusal syptoms.

I'm positive a MAN oh PAUSE is also warranted...so you LADIEs in
Waiting... MARRY a good JUAN...

And be sure he's your BEST friend and not SOME sexual PEST... without
consideration for your situation.

Life isn't EASY don't make it HARD... LoL

er!

What about cancer?

Now this is harder... and finding a STRAIGHT answer from big PHARMA is
easy either.

http://www.chiro.org/nutrition/ABSTRACTS/What_is_Black_Cohosh.shtml

[...] Chemical Composition

Black cohosh contains cimicifugin (macrotin) which has estrogenic
effects. Also found in assay are acetein (antihypertensive effects)
and ferulic/isoferulic acids (anti-inflammatory effects). The
following components can also be found: isoflavones, salicyclic acid,
tannins, resins, starch, and sugars.

[...] Anti-inflammatory effects

Ferulic and isoferulic acid, both found in black cohosh, are potent
inhibitors of interleukin-8, which is produced upon stimulation of an
inflammatory response and serves as a chemoattractant for
neutrophils. By inhibiting these acids, inflammation is inhibited.
<snip>


http://www.mayoclinic.com/health/black-cohosh/NS_patient-blackcohosh/DSECTION=related-terms
[...] Note : Do not confuse black cohosh ( Cimicifuga racemosa ) with
blue cohosh ( Caulophyllum thalictroides ), which contains chemicals
that may damage the heart and raise blood pressure. Do not confuse
black cohosh ( Cimicifuga racemosa ) with Cimicifuga foetida ,
bugbane, fairy candles, or sheng ma; these are species from the same
family (Ranunculaceae) with different effects.
<snip>

Looks like the susan komen folks copied the mayo folks?

http://ww5.komen.org/BreastCancer/Blackcohosh.html

[...] The mechanism of action of black cohosh remains unclear and the
effects on estrogen receptors or hormonal levels (if any) are not
definitively known. Recent publications suggest that there may be no
direct effects on estrogen receptors, although this is an area of
active controversy. Safety and efficacy beyond six months have not
been proven, although recent reports suggest safety of short-term use,
including in women experiencing menopausal symptoms for whom estrogen
replacement therapy is contraindicated. Nonetheless, caution is
advisable until better-quality safety data are available. Use of black
cohosh in high-risk populations (such as in women with a history of
breast cancer) should be under the supervision of a licensed
healthcare professional.
<snip>

A google search: black cohosh ferulic acid cancer

The mayo and komen come up 1 and 2.
<snip>

And by adding in resveratrol we get a prostate hit:

http://www.prostate.net/prostate-health-supplements-a-z/black-cohosh/
Black cohosh

BY DR. GEO ESPINOSA, N.D., L.AC, CNS, RH (AHG)

Black cohosh (Actaea racemosa, formerly Cimicifuga racemosa) is a
perennial plant native to North America and a member of the buttercup
family. Remedies of black cohosh, which are prepared from the roots
and rhizomes, were used historically for gynecological conditions,
kidney disorders, malaria, cough, malaise, and constipation.

Research has identified a substance called fukinolic acid as having
estrogenic activity in vitro. (Kruse 1999) The herb also contains
other active compounds, including triterpene glycosides, resins, and
isoferulic acid. (Mills 2000) Black cohosh is also believed to contain
phytoestrogens, which may help reduce estrogen in the body.
(University of Maryland)

Black cohosh may have a role in prostate cancer as well. At the
University of Gottingen, scientists evaluated the impact of black
cohosh extract on human prostate cancer cells in mice. Following
inoculation with 1 million prostate cancer cells, 12 of 18 mice
developed tumors, while only 5 of 18 mice treated with black cohosh
developed tumors. The tumors in the five treated mice were
significantly smaller than those in the nontreated mice. (Seidlova-
Wuttke 2006)

In a subsequent study at the University of Gottingen, investigators
isolated a substance called petasiphenone from black cohosh. In the
lab, they found that petasiphenone inhibited growth of human prostate
cancer cells. (Jarry 2007)

Black cohosh extracts are standardized to contain triterpene saponins,
which typically appears on the label as 26-deoxyactein. Before taking
black cohosh, men should consult their physician.

References

Jarry H et al. Petasiphenone, a phenol isolated from Cimicifuga
racemosa, in vitro inhibits proliferation of the human prostate cancer
cell line LNaP. Planta Med 2007 Feb; 73(2): 184-87

Kruse SO et al. Fukiic and piscidic acid esters from the rhizome of
Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic
acid. Planta Medica 65: 763-764, 1999.

Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh:
Churchill Livingstone, 2000: 303-9.

Seidlova-Wuttke D et al. Inhibitory effects of a black cohosh
(Cimicifuga racemosa) extract on prostate cancer. Planta Med 2006 May;
72(6): 521-26
<snip>


^^^^^^^^^^^^^^^^^^^^^

This is also redux to the last JXR post:


Mucins (mucus) in the Gi tract go haywire years before (sometimes or
all?) you
go south with cancer.

If so then in vino veritas (or Japanese Knotweed) means LESS cancer.

two possibly salient hits.

pde4 inhibitors?

mucins + resveratrol - 2 hits -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=mucins%20resveratrol

#1 of 2

http://www.ncbi.nlm.nih.gov/pubmed/19818280
Nutrition. 2009 Nov-Dec;25(11-12):1169-76.
Influence of dietary resveratrol on early and late molecular markers
of 1,2-dimethylhydrazine-induced colon carcinogenesis.

Sengottuvelan M, Deeptha K, Nalini N.

Source
Department of Biochemistry and Biotechnology, Annamalai University,
Annamalainagar, Tamilnadu, India.

Abstract
OBJECTIVE:
Colon cancer is an exceptionally aggressive disease, and the use of
natural or synthetic substances to prevent or decrease cancer risk
without adverse effects remains a major challenge. In this study, the
mechanistic basis for the chemopreventive effect of resveratrol (Res)
on 1,2-dimethylhydrazine-induced colon carcinogenesis in an rat model
was evaluated.
METHODS:
Rats were randomized into six groups. Group 1 were control rats, group
2 were control rats that received Res (8mg/kg of body weight orally
every day), and rats in groups 3-6 were treated once per week with 1,2-
dimethylhydrazine (20mg/kg of body weight, subcutaenously, 15 times).
In addition, groups 4-6 received Res (as in group 2) in three dietary
regimens: initiation, postinitiation, and entire period. All rats were
sacrificed after 30 wk and the degree of inflammation, cell
proliferation, apoptosis, and mucosal integrity was evaluated.
RESULTS:
Res supplementation during the entire period significantly amended the
expression of inflammatory, cell proliferative, and apoptotic
biomarkers such as cyclo-oxygenase-2, ornithine decarboxylase,
caspase-3, and heat shock proteins 70 and 27. Moreover, supplementing
Res for the entire study period modulated the colonic mucosal protein
mucin 1 and 2 expression.
CONCLUSION:
The results clearly indicate that chronic Res supplementation
inhibited the colon cancer development through modulating the early
and late events of carcinogenesis and helped to maintain the colonic
mucosal integrity. Thus our study demonstrates that the
chemopreventive efficacy of Res could be attributed to its action on
multiple direct targets of carcinogenesis.

PMID: 19818280

2 of 2:


http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10644316/?tool=pubmed
Gut. 2000 Feb;46(2):218-24.
Mucin secretion is modulated by luminal factors in the isolated
vascularly perfused rat colon.

Barcelo A, Claustre J, Moro F, Chayvialle JA, Cuber JC, Plaisancié P.

Source
INSERM U45, Hôpital Edouard Herriot, Lyon, France.

Abstract
BACKGROUND:
Mucins play an important protective role in the colonic mucosa.
Luminal factors modulating colonic mucus release have been not fully
identified.

AIM:
To determine the effect of some dietary compounds on mucus discharge
in rat colon.

METHODS:
An isolated vascularly perfused rat colon model was used. Mucus
secretion was induced by a variety of luminal factors administered as
a bolus of 1 ml for 30 minutes in the colonic loop. Mucin release was
evaluated using a sandwich enzyme linked immunosorbent assay supported
by histological analysis.

RESULTS:
The three dietary fibres tested in this study (pectin, gum arabic, and
cellulose) did not provoke mucus secretion. Luminal administration of
sodium alginate (an algal polysaccharide used as a food additive) or
ulvan (a sulphated algal polymer) induced a dose dependent increase in
mucin discharge over the concentration range 1-25 mg/l (p<0.05 for 25
mg/l alginate and p<0.05 for 10 and 25 mg/l ulvan). Glucuronic acid
and galacturonic acid, which are major constituents of a variety of
fibres, produced significant mucin secretion (p<0.05). Hydrogen
sulphide and mercaptoacetate, two sulphides produced in the colonic
lumen by microbial fermentation of sulphated polysaccharides, did not
modify mucin secretion. Among the short chain fatty acids, acetate
(5-100 mM) induced a dose dependent release of mucus (p<0.05 for 100
mM acetate). Interestingly, butyrate at a concentration of 5 mM
produced colonic mucin secretion (p<0.05), but increasing its
concentration to 100 mM provoked a gradual decrease in mucus
discharge. Propionate (5-100 mM) did not induce mucin release. Several
dietary phenolic compounds (quercetin, epicatechin, resveratrol) did
not provoke mucus discharge.

CONCLUSIONS:
Two algal polysaccharides (alginate and ulvan), two uronic acids
(glucuronic acid and galacturonic acid), and the short chain fatty
acids acetate and butyrate induce mucin secretion in rat colon. Taken
together, these data suggest that some food constituents and their
fermentation products may regulate the secretory function of colonic
goblet cells.

PMID: 10644316
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10644316/?tool=pubmed


============================================

http://www.ncbi.nlm.nih.gov/pubmed/22435425
Int J Dermatol. 2012 Apr;51(4):389-398. doi: 10.1111/j.
1365-4632.2011.05154.x.
The roles of cells and cytokines in the pathogenesis of psoriasis.

Coimbra S, Figueiredo A, Castro E, Rocha-Pereira P, Santos-Silva A.

Source
Biochemistry Laboratory, Department of Biological Science, Faculty of
Pharmacy and Institute of Molecular and Cellular Biology (Instituto de
Biologia Molecular e Celular [IBMC]), University of Porto
(Universidade do Porto), Porto, Portugal Centre for Investigation into
Health Technologies (Centro de Investigação das Tecnologias da Saúde
[CITS]), Northern Polytechnic Health Institute (Instituto Politécnico
da Saúde Norte), Cooperative Higher Education, Polytechnic and
University (Cooperativa de Ensino Superior, Politécnico e
Universitário [CESPU]), Gandra-Paredes, Portugal Dermatology Service,
Coimbra University Hospital (Hospitais da Universidade de Coimbra),
Coimbra, Portugal Centre for Investigation in Health Sciences (Centro
de Investigação em Ciências da Saúde [CICS]), University of Beira
Interior (Universidade da Beira Interior), Covilhã, Portugal.

Abstract
Psoriasis is considered an immune chronic disease in which T cells are
accepted as important. Nowadays, it is believed that psoriasis is most
likely a T helper (Th)1/Th17 induced inflammatory disease. However,
some other cells, such as endothelial cells, dendritic cells,
monocytic cells, neutrophils, keratinocytes, and several cytokines,
appear to have, at different stages of the disease, an important role
in its pathogenesis. For instance, the response to psoriasis therapy
is dependent not only on the inactivation of Th1 and Th17 immune
responses but also on the inactivation of dendritic cell products.
Moreover, interleukin (IL)-23 deregulation appears to be an
independent factor in the pathogenesis of psoriasis. Indeed,
currently, the IL-23/Th17 axis is believed to be crucial in psoriasis
pathogenesis, and its inhibition appears to be important for
therapeutic achievement. This review presents the roles and
interactions of cells and cytokines that are related to psoriasis
pathogenesis.

PMID: 22435425

82 hits: IL-23 Th17 axis -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=IL-23%20Th17%20axis

19 of 82 - have: psoria*
http://www.ncbi.nlm.nih.gov/pubmed?term=IL-23%20Th17%20axis%20psoria*

270 hits - IL-23 + psoria* - pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=IL-23%20%20psoria*

3 of 270 of these have LPS
http://www.ncbi.nlm.nih.gov/pubmed?term=IL-23%20psoria*%20LPS

242 hits -- IL-23 + LPS -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=IL-23%20%20LPS

#1 of 242 is in the black cohosh pancan thread:

Here:
Mon, Mar 19 2012 3:19 pm
Subject: Killing CANCER: Black Cohosh--Actaea racemosa (γ-secretase &
ILL-e-fects?), Ferulic acid (Rhizoma of Cimicifuga), Figwort
(Scrophulariaceae), Sulfonylureas, EDHF, polyphenols, kaempferol
(flavonoid), Gamma-oryzanol ->rice bran oil --> LPS - +++
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=PMID%3A+22379034+&start=0&

[...] http://www.ncbi.nlm.nih.gov/pubmed/22379034
Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells
Potentiates Th17-Mediated Immunity.
Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M,
Herrada AA, Lladser A, Bernales S, Pacheco R.
J Immunol. 2012 Feb 29.
PMID: 22379034

^^^^^^^^^^^

404 hits: LPS + retrovirus -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=%20LPS%20retrovirus



OK... must go FEAST and not FAMINE... will i take some


www.longevinex.com...?

YEs... it's the BEST...


So is JXR on the BEST YET?

No cancer or autoimmune or... bad psor genes?

WeLL?

we can't change your genetics... jxr..

We can do the epigenetic fix... or at least dietary-ILLy---> try.

caveats being....

excess mucus in the Gi tract that goes south..

I hope mazmanian is working on this... it's been
forever since i've seen a new abstract from the caltech lab.



randall.... crack is whack... so what is cocaine? it's INSANE? cardio
disturbing? Sad?