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Abstract

Metadichol ® is a nano formulation of long-chain lipid alcohols derived from food It is a inverse agonist of Vitamin D receptor (VDR), Aryl hydrocarbon receptor (AHR), and ROR gamma (RORC) that could have beneficial effects on skin diseases. We now present case studies of patients with various skin diseases who has symptoms mitigated on treatment with Metadichol. The proposed mechanism is that Metadichol by its actions on the above mentioned nuclear receptors affects Th1, TH2,Th 17, IL 17 and IL22 and IL 23 pathways that exacerbate many Skin diseases. Metadichol is the first molecule to successfully navigate around the problems involved with promiscuous ligands and targets. It fulfills the goals of the emerging field of Polypharmacology i.e a single drug is able to bind to multiple targets beyond the "one drug, one target" concept. We show how Metadichol is an innovative treatment for treating multiple skin diseases like eczema, acne, diabetic wounds viral and bacterial infection and also improving skin texture. Metadichol ® is a safe non toxic low cost solution and is an alternative to numerous clinical candidates in combating over 3000 skin diseases.
Open Access
Journal of Clinical & Experimental
Dermatology Research
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ISSN: 2155-9554
Raghavan, J Clin Exp Dermatol Res 2018, 9:1
DOI: 10.4172/2155-9554.1000445
Volume 9 • Issue 1 • 1000445
J Clin Exp Dermatol Res, an open access journal
ISSN: 2155-9554
*Corresponding author: PR Raghavan, Nanorx Inc, P.O. box 131,Chappaqua,
New York,1051, USA, Tel: +19146710224; E-mail: raghavan@nanorxinc.com
Received January 22, 2018; Accepted February 26, 2018; Published March 12,
2018
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many
Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-9554.1000445
Copyright: © 2018 Raghavan PR. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Keywords: Metadichol; Psoriasis; Eczema; Acne; Warts; Diabetic
wounds; VDR; Vitamin D; Calcitriol; Inverse agonist; TH1; TH2; ROR
gamma T; (RORγt); Interleukin (IL)-17; IL-23; Tumor necrosis factor
(TNFα); IL-17–producing T (T17) cells; T helper ()1 cells; 22 cells
Introduction
The skin is the largest organ of the body that protects against
mechanical and chemical threats, it provides innate and adaptive
immune defenses, enables thermo-regulation and vitamin D
production, and acts as the sensory organ of touch (1). Skin is
frequently damaged because it is directly in the 'firing line' and, is a
significant cause of global disease burden, affecting millions of people
worldwide. There are more than 3000 known diseases of the skin (2).
Aging, environmental and genetic factors, and trauma can result in the
development of a diverse set of skin diseases (3,4).].
A cosmetically disfiguring disorder can have a significant impact
and can cause considerable discomfort and disability. Most of the
chronic skin diseases like Atopic Eczema, Psoriasis, Vitiligo and leg
ulcers, are not immediately life-threatening but are an enormous
burden on health status and quality of life issues, physical as well as
mental. One in four Americans (85 million) were seen by a physician
for skin disease in 2013. In 2013, skin disease resulted in direct health
care costs of $75 billion and indirect lost opportunity costs of $11
billion. Another study estimated the cost of Psoriasis alone in the US to
be $112 billion [5]. .
Skin diseases become more prevalent as population ages worldwide
[6], which directly affects the overall health (Figure 1). A wellness and
prevention approach to protecting the skin can substantially reduce the
incidence of non- melanoma and other skin cancers [7]. Maintaining a
healthier skin enables better health outcomes leading to a more active
and engaged lives.
There are many Biologic agents used today to treat different
cutaneous diseases. Antibiotics like Tetracycline, Rifampicin Retinoids
like Acitretin, Anti-androgens like Metformin and Spironolactone and
immunosuppression drugs like Cyclosporine. Some mAbs are in in in
use for psoriasis, atopic dermatitis, melanoma, and other skin diseases
target IL-17 and TNF alpha [8,9]. Many promising target therapies are
under study, including bio-similars that reduce costs associated with
these originator monoclonal antibodies. Despite progress in clinical
dermatology a more through pathophysiology of diverse skin
conditions is needed to target 3000 skin diseases with a cheaper and
cost-effective solution (Figure 1).
Metadichol [10] is a nano lipid formulation of long-chain
naturally alcohols. It is an inverse agonist of VDR (Vitamin D
receptor) AHR (Aryl hydrocarbon receptor), RORC (Retinoic
acid receptor gamma) and a TNF alpha inhibitor. We have recently
documented how Metadichol is effective against Psoriasis [11]. The
gene cluster targeted by Metadichol are predicted by Topp gene
cluster program [12] to target other skin diseases as shown in Figure
2. One can also see that Skin diseases are related to each other as
predicted by Disease Connect [13], which is based on curated
experimental data as shown in Figure 3.
Research Article
Metadichol® and Healthy Skin: One Approach many Possible Cures
PR Raghavan*
Nanorx Inc, P.O Box, 131, Chappaqua, New York,10514, USA
Abstract
Metadichol ® is a nano formulation of long-chain lipid alcohols derived from food It is a inverse agonist of Vitamin
D receptor (VDR), Aryl hydrocarbon receptor (AHR), and ROR gamma (RORC) that could have beneficial effects on
skin diseases. We now present case studies of patients with various skin diseases who has symptoms mitigated on
treatment with Metadichol. The proposed mechanism is that Metadichol by its actions on the above mentioned
nuclear receptors affects Th1, TH2,Th 17, IL 17 and IL22 and IL 23 pathways that exacerbate many Skin diseases.
Metadichol is the first molecule to successfully navigate around the problems involved with promiscuous ligands
and targets. It fulfills the goals of the emerging field of Polypharmacology i.e a single drug is able to bind to multiple
targets beyond the "one drug, one target" concept. We show how Metadichol is an innovative treatment for treating
multiple skin diseases like eczema, acne, diabetic wounds viral and bacterial infection and also improving skin
texture. Metadichol ® is a safe non toxic low cost solution and is an alternative to numerous clinical candidates in
combating over 3000 skin diseases.
Figure 1: Representation of International Classication of Diseases, Ninth
Revision (ICD-9) diagnosis codes.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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ISSN: 2155-9554
with a p-value less 10-9. Given this high degree of correlation predicted.
We decided to test this hypothesis below by treating Metadichol on
patients with various skin diseases.
Case Studies
Presented are case studies related to skin diseases. Metadichol (5
mg/ml) is sprayed on the aected area and or taken orally. In some
cases, Metadichol gel is was used the concentration was 2.5 mg/gm and
applied to aected areas (Figures 4-38).
Results and Discussion
The results confirm the theoretical prediction as show in
Figures 2 and 3. The clinical case studies presented suggest that
there is a common pathway through which Metadichol acts to
mitigate the condition be it eczema or viral skin disease like herpes
or diabetic wound healing and skin rejuvenation. Metadichol binds
to Vitamin D receptor (VDR) as an inverse agonist and seems to
mimic the well-known actions of 1,25 dihydroxy Vitamin D3
(Vitamin D3) the natural agonist of VDR. The effect of Vitamin
D3 are mediated by its binding to the vitamin D receptor (VDR).
Once it binds its ligand, VDR dimerizes with a RXR (retinoid X
receptor). These VDR-RXR hetero-dimers bind to vitamin D
response elements present on target genes [14-16].
In addition to transcriptional activation, the hetero-dimers
can displace the nuclear factors of activated T cells resulting in
repression of cytokine-related genes [17].
Vitamin D3 suppresses Th-1 cell proliferation leading to the
lowered production of interferon gamma and interleukin-2 [18-20].
Lower levels of circulating cytokines leads to less antigen presentation
by dendritic cells, in addition to less T lymphocyte recruitment and
proliferation. Expression of Th-2 associated cytokines, including
interleukin-4 are increased by Vitamin D3. Overall, vitamin D3
polarizes the adaptive immune system away from Th-1 and toward
Th-2 responses. Also, Vitamin D3 suppresses IL- 17 production via
direct transcription and suppression of IL-17 gene expression [21].
The majority of studies done so far indicate an inverse
relationship between the severity of atopic dermatitis, eczema and
vitamin D levels. Individuals with AD and eczema treated with
vitamin D led to decreased severity of the disease [22,23].
Acne vulgaris is a skin disorder affecting millions of
people worldwide. Inflammation resulting from the immune
response targeting Propionibacterium acnes (P. acnes) has a
significant role in acne pathogenesis. It has been demonstrated that
P. acnes are a potent inducer of Th17 and that 1,25OH2D inhibits
P. acnes-induced Th17 differentiation, and thereby could be
considered as a useful tool in modulating acne [24].
Herpes and shingles are caused by herpes family of viruses,
which are generally dormant but they can reactivate under certain
conditions. Herpes simplex virus-1 (HSV-1) and herpes simplex
virus-2 (HSV-2) can cause oral and genital herpes. Varicella-zoster
virus results in chickenpox in children and shingles later in life.
The anti-viral effects of vitamin D could be explained by it
inducing cathelicidin (in the form of LL-37) and also human
Figure 2: The gene cluster targeted by Metadichol by Topp gene cluster program to target other skin diseases.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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ISSN: 2155-9554
beta-defensin 2, and the likely release of reactive oxygen species [25].
Vitamin D has an essential role in innate immune
response modulation. The toll-like receptors (TLRs) in
macrophages, polymorphonuclear cells, monocytes, and epithelial
cells are central to the innate immune response [26,27]. TLRs
recognize pathogen-
associated molecular patterns associated with infectious agents. TLR2
recognizes the lipopolysaccharides of bacteria and also the viral
proteins and nucleic acids. Upon recognition, activated TLRs release
cytokines that induce expression of antimicrobial peptides and reactive
oxygen species. Metadichol has been shown to be active against MRSA
bacterial infection [28].
Figure 3: Relation between Skin diseases as predicted by Disease Connect which is based on curated experimental data.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Skin wounds require vitamin D3 to protect against infections
to initiate the normal repair process. Vitamin D has an indirect
role in wound healing due to its effect on improved glycemic
control in 12 weeks among patients with diabetic foot injury and
reduced inflammatory markers like ESR, hS-CRP [29]. Vitamin D
deficiency
Figure 4: Female-45 with eczema on her right hand for more than ten years.
She had tried many medicines and topical drugs but with no success.
Treated with Metadichol Nano-Spray in the mouth and on hand for 8 weeks.
Her hand eczema healed completely.
Figure 5: A 12 years old girl with painful eczema under her left foot for a year.
Treated by doctors with different cream and drugs but with no success. Had
difculty walking. Treated with Metadichol by spraying (5 sprays a day) in the
mouth and on eczema three times a day. Day 10 her eczema foot healed to the
extent and was able to walk without any discomfort or pain.
Figure 6: Female aged 18 years old with Eczema for six year. Treatment
by spraying leg with Metadichol. Healed in 4 weeks.
Figure 7: 30 year old Eczema patient five sprays in the mouth (5 mg) 3 times
a day and on face three times a day. Completely healed in 30 days.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 8: Male 40 Eczema of hand Applied gel on affected areas twice a day.
Figure 9: Male 40 Eczema of hand. Sprayed Metadichol on the affected area.
Conditions cleared in 7 days.
Figure 10: Male 36 years old with eczema. Progress with Metadichol gel day
1 to 42. Gel treatment stopped. After ve years no recurrence.
Figure 11: M-50. Type 2 diabetic for ten years. Left index toe was amputated.
Sprayed Metadichol on affected area 3 times a day and 5 mg per day orally.
compromises the body’s innate immune system, making a patient
more vulnerable to microbes and infections [30]. Vitamin D3 role in
innate immunity is to enable keratinocytes to recognize and respond
to bacteria and to protect wounds against infection [31] Metadichol as
we documented earlier has a powerful effect on diabetic patients
[32,33]. Metadichol is an agonist of GPR 120 [34]. This is another
pathway though which it can act as shown by Arantes El et al. [35] that
the topical use of GPR 120 agonists like polyunsaturated fatty acids
(PUFAs) can accelerate skin wound healing. Da Younz et al. [36] have
shown that GPR120 agonist treatment of high-fat diet–fed obese mice
causes improved glucose tolerance, decreased hyperinsulinemia,
increased insulin sensitivity and decreased hepatic steatosis. For
wound healing, a decrease in glucose levels leads to improved
outcomes.
Atopic Dermatitis (AD) is a common chronic inflammatory skin
disease where VDR signaling is essential to be important not only in
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 12: Female 61. The diabetic wound on feet did not heal over two years
could not walk. Metadichol sprayed on wound three times a day. Now walks
slowly with the heel raised without pain.
Figure 13: Female 83 diabetics for 25 years. Left foot was amputated at age
76. Right foot has a diabetic wound that did not heal. Sprayed Metadichol on
affected area for two months. The diabetic wound on right foot healed.
Figure 14: Middle-aged man with a painful tumor on his neck for over 20
years. His tumor could not be operated as he is a Diabetic Metadichol 5
mg per day orally and sprayed on wound . After using Metadichol, the
tumor pain was gone within 30 minutes. Yellow pus and blood discharged
after a day during the first two weeks. After using Metadichol for one month,
the wound is almost healed.
Figure 15: Diabetic Wound-Calf. Subject: Female-52. Had wound for more
than six months. It started as a small spot and was prescribed Calapure by a
physician. The patient stated the wound always bleed after a hot bath. When
scratched, it begins to look very “angry” and red. Metadichol topically and
orally twice a day.
the immune system but also in particular keratinocytes to regulate
skin homeostasis and epidermal barrier function. Hartmann et al. [37]
showed that regulatory T cells have a role in the AD, are increased in the
skin of VDR agonist-treated mice and induction of skin barrier gene
and antimicrobial peptide gene expression in skin lesions of the treated
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 16: Patient M-65. Carbuncle is a cluster of boils, which drains pus
onto the skin. It is usually caused by bacterial infection, most commonly with
Staphylococcus aureus or Streptococcus pyogenes, which can turn lethal.
Diagnosed and treated with antibiotics for one year without improvement.
Metadichol @ 5 mg per day sprayed on the wound.
Figure 17: Male-45 Herpes on his back and stomach. Sprayed with
metadichol.
Figure 18: Male 34 fungal infection and skin peeling painful while
walking. Applied Metadichol gel on affected are. Pain eased after day 1.
Figure 19: Female, 33 years old. Warts on the palm of hands and fingers.
She experienced a sudden outbreak of warts on her hands due to an
immune response to toxins in the body. Over 50, dry and rough spots were
developing into warts on all ngers: Tiny, brown specks appeared all over
palms and fingers, forming into wart heads. Small, circular-shaped spots
were scaly and dry. These spots were the beginning of wart heads
forming: She noted it looked like small coffee grinds all over palms: Treated
by spraying Metadichol on each hand, two times per day. Orally, two sprays
(2 mg) per day.
mice. Targeting the VDR with low-calcemic agonists could be a new
feasible approach for the AD.
Alopecia results when the immune system attacks the hair follicles,
resulting in patterned hair Cianferotti et al. found that vitamin D
receptors in the hair follicles a play a role in normal hair cycling loss
[38]. Mutation of the VDR, in humans and mice, results in alopecia.
e actions of VDR that prevent alopecia are ligand-independent.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 20: Male, ten years old. Condition: Keratosis Pilaris, Eczema and toe
injury scrape from swimming pool. Topically, spray twice a day on the affected
area. Rash and inammation deceased. Scabs faded to healthy skin.
Figure 21: Hand Foot Mouth Virus (HMF). Female, 35 years old contracted
HMF virus mostly on hand from her son (see gure 22). She developed red
itchy sores on her hands. She was severely allergic to Benadryl. Metadichol
Topically and orally 4 times per day.
Figure 22: Hand Foot Mouth Virus . Male five years old. Pus oozed from the
sores. It was itchy and painful to the point of crying. Metadichol was used
topically on affected areas and orally up 5 sprays (5mg) 4 times per day.
After one day of using Metadichol sores began to scab and dry out. Less
itching on 5th-day, sores drying out and shrinking in size, less redness.
Metadichol helped reduce the pain, relieved itching, eased the oozing sores,
and stopped the spread of the lesions.
Figure 23: F-14 years old conjunctivitis sprayed Metadichol into eye at 24 h
the area around eye turned red and at 36 h completely cleared her eyes.
Mutations in the VDR that disrupt the ability of the unliganded VDR
to suppress gene transcription are hypothesized to lead to disruption if
the hair cycle that ultimately leads to alopecia [39]. It like hair follicle
cycling is dependent on unliganded actions of the VDR [40].
Vitamin C is an antioxidant useful for preventing and treating
skin aging. It stimulates the barrier function of the endothelial cells
and is proven to have photo protective eects [41,42]. What hampers
its uses widely is the inability to delivery into the dermis for collagen
production [43].
Metadichol over comes this delivery problem as it increases
Vitamin C levels [44,45] over and beyond what is achieved by oral
supplementation. Vitamin C is present at cutaneous level, displaying
antioxidant, anti-inammatory, photoprotective properties, and is
a known bio stimulator of collagen synthesis [46]. It has a role in the
maintenance of dermal collagen, preventing the inactivation of enzymes
involved in the biosynthesis of collagen, hydroxylase, and lysine [47].
Vitamin D3 has an essential role in mitigating many skin diseases
be it production of AMP’s,  17 inhibition and directing immune
response towards a 2 outcome [48]. Metadichol binds to VDR as an
inverse agonist and based on the result mimics the action of Vitamin
D3. Also, its eects are enhanced by its inverse agonist actions on
RORC that is involved in the 17 expression.
Metadichol is an inverse agonist of AHR which is involved
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 24: Patient M-58 ganglion cyst that he could not rid with surgery
every year for two years and it reappeared in days after each operation.
Applied Metadichol gel and it healed in 12 weeks. Five years since last
application of gel and no reappearance of Cysts.
Figure 25: M-35. Finger wound that did not heal. sprayed with
Metadichol twice a day.
Figure 26: M-30. Deep Laceration on the arm and Metadichol sprayed
on affected areas twice a day.
Figure 29: Male 85 bed sore infection in Hospital. Gel applications on
the affected area. Complete healing on 3rd day.
Figure 27: M-25. Thumb Injury caused by a car door. Sprayed with
Metadichol complete healing on day 3.
Figure 28: M-65, while cooking spilled hot oil on his hand. Treated
with Metadichol sprayed twice a day on affected areas.
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 30: Female 35. Dog bite. Sprayed Metadichol on affected area.
Figure 33: F-24 Pimples and acne and disfigures skin. Treated with gel.
Figure 34: F-36 acne and pimples. Metadichol gel twice a day and
vast improvement in skin seen after three days.
Figure 32: F-58 years old. Skin treatment with Metadichol Gel twice a day.
Figure 31: F-29. Disfigured skin. Sprayed Metadichol on affected areas..
in adaptive responses against UVB or topical chemicals and plays
a role in maintaining homeostasis of skin cells and skin immunity.
AHR ligands have applications in the prevention and treatment of
skin disease [49].
Metadichol is an inhibitor of TNF alpha a significant
cytokine of inflammatory diseases of the skin. The anti-TNF
alpha arsenal is currently dominated by Etanercept, a fusion
protein composed of a soluble TNF alpha receptor, and
infliximab, a chimeric monoclonal antibody. Many
dermatological diseases will probably benefit from these new
treatments.These are expensive, with unknown long-term side
effects, A small number of Studies have already demonstrated
their effects in cutaneous and articular psoriasis. Encouraging
sporadic results suggest other potential indications of Behcet’s
disease, bullous dermatitis, neutrophilic dermatitis, toxic
epidermal necrolysis, and systemic vasculitis [50].
Metadichol is also an inhibitor of ICAM 1 and expression
of cell-adhesion molecules are known to contribute to
inadequate inflammatory response seen in inflammatory skin
diseases. The epidermis of patients with inflammatory skin
diseases exhibits increased expression of ICAM 1 [51].
Citation: Raghavan PR (2018) Metadichol® and Healthy Skin: One Approach many Possible Cures. J Clin Exp Dermatol Res 9: 445. doi:10.4172/2155-
9554.1000445
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Figure 35: Male 35. Male 35. Knife wound that needed 20 stitches. Scar did
not disappear after one year. Applied Gel and most of the ugly scar
disappeared and with new skin formation.
Figure 36: M-25 with a wound on arm. Metadichol gel applied on
affected area led to elimination of skin marks.
Figure 37: Female 17 with eczema since she was a baby. Treated with
Metadichol orally and on skin. 4 days later, her eczema spots showed vast
improvement
Conclusion
Given that there are approximately 50000 diseases [52] that
confront humanity. The dogma ‘one drug’ ‘one target’ ‘one disease’ is
not a viable option. A Poly pharmacological approach [53-55], i.e.,
single drug acting on multiple targets of a unique disease pathway or a
single drug working on multiple targets on multiple disease pathways
is an emerging approach that needs to be exploited.
Metadichol is first in this class of molecules. It acts on varied
diseases and through multiple pathways. It is also a food-based
ingredient devoid of any side effects and could be the harbinger of
changes that can impact the healthcare industry. Metadichol by its
actions on VDR, AHR, RORC,TNF alpha and ICAM1 efficiently shuts
down the many pathways that are involved in the inflammatory
process in the pathogenesis of skin diseases. This explains why
Metadichol is useful in many types of skin diseases based on the
results we have presented. Given that there are over 3000 skin diseases
and it would be virtually impossible to treat them one by one,
Molecules like Metadichol a safe food-based ingredient will hopefully
fulfill the quest to reduce the burden of skin diseases worldwide.
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9554.1000445
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Volume 9 • Issue 1 • 1000445
J Clin Exp Dermatol Res, an open access journal
ISSN: 2155-9554
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... Enriched expression of IRS1, IRS2 and GLUT4 on treatment of UC cells with has not been reported so far and has a role in diabetes treatment. We recently presented clinical case studies that showed the effectiveness of Metadichol in treatment of diabetes and related complications like wound healing [20][21][22]. IRS1 and IRS2 have been shown to play an essential role in the insulin signaling pathway [23]. Increase in IRS2 expression in β-cells has been shown to be essential for growth and function [24]. ...
... Since adult stem cells are present in PBMCs which have similar expression profiles to UBC [39], one could expect similar actions by Metadichol on these cells leading to observed improvements that we have documented in diabetes patients [21][22][23]. The study shows highly related biologically functional gene clusters are the key in targeting diseases. ...
Article
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Insulin and IGF signaling require a family of scaffold proteins, also called as Insulin Receptor Substrate (IRS) proteins to integrate extracellular signals into intracellular responses, leading to cellular effects. Two main IRS proteins in humans are IRS1 and IRS2 and are widely expressed in most human and mammalian tissues. In this study, IRS1, IRS2, GLUT4 gene expression is quantified in Umbilical Cord (UC) cell line by semi quantitative- PCR. The internal control β-actin was used to normalize the IRS1, IRS2, GLUT4 gene expression levels. This is the first example of UC cells being induced by a ligand in expressing genes that regulate glucose and insulin levels. Metadichol® treatment at different concentrations on UC cells showed upregulation of IRS1, IRS2 and GLUT4. 100 pg/mL concentrations showed the highest upregulation of IRS1, IRS2 and GLUT4 expression. 1 ng and 100 ng/mL treatment showed marginal. Metadichol® is in addition a TNF alpha inhibitor and also inhibits Plasminogen Activation Inhibitor (PAI1) also known as SERPINE1. These genes play an important role in diabetes. The experimental results fully correlated with curated literature data using Bioinformatics software. Network analysis show the uniqueness of shared genes, IRS1, IRS2, GLUT4, TNF, PAI1, acting through multiple pathways that target multiple diseases.
... This paper deals with Metadichol ® expression on UCB cells leading to increased CD33 expression similar to what we saw in CD34 expression. The increased expression observed with CD33 could be one possible mechanism that could explain its diverse pharmacological actions of Metadochol ® on multiple diseases [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. ...
... We have shown previously that Metadichol ® binds to VDR whose natural ligand is Calcitriol. We have published Metadichol's action on biomarkers implicated in various diseases [25][26][27][28]. It exhibits antimicrobial activity against parasites, viruses, and bacteria. ...
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CD33 also known as Siglec-3 is endogenously expressed in stem cells and is a marker for the myeloid lineage of cells. Increased expression of CD33 thus allows it to bind to any Sialic Acids (SIAs). These acids are binding sites for pathogens and toxins. By binding to these acids, CD33 can prevent invasion of hosts by these pathogens. Down-regulation of CD33, increase the release of the pro-inflammatory cytokine TNF-α by monocytes that increases reactive oxygen species that are involved in diseases like diabetes mellitus, Alzheimer's, cardiovascular diseases asthma, and in various cancers. The up-regulation of CD33 using Metadichol ® was studied using Wharton's Jelly Mesenchymal Stem Cells (MSCs) isolated from human umbilical cord and were grown in p-35 dishes until confluent and treatment was carried out with different concentrations. One dish was untreated and considered as control. The treated and untreated cells were analyzed using Flow Cytometry. The cells treated at 100 pg of Metadichol ® has shown the highest increase (>400 fold) in CD33++ expression (48.77%) compared to untreated control (0.11%).
... Enriched expression of IRS1, IRS2 and GLUT4 on treatment of UC cells has not been reported so far and has a role in diabetes treatment. We recently presented clinical case studies that showed the effectiveness of Metadichol in treatment of diabetes and related complications like wound healing [20][21][22]. IRS1 and IRS2 have been shown to play an essential role in the insulin signaling pathway [23]. Increase in IRS2 expression in β-cells has been shown to be essential for growth and function [24]. ...
... Since adult stem cells are present in PBMCs which have similar expression profiles to UBC [40], one could expect similar actions by Metadichol on these cells leading to observed improvements that we have documented in diabetes patients [21][22][23]. The study shows highly related biologically functional gene clusters are the key in targeting diseases. ...
Article
Full-text available
Insulin and IGF signaling require a family of scaffold proteins, also called as Insulin Receptor Substrate (IRS) proteins to integrate extracellular signals into intracellular responses, leading to cellular effects. Two main IRS proteins in humans are IRS1 and IRS2 and are widely expressed in most human and mammalian tissues. In this study, IRS1, IRS2, GLUT4 gene expression is quantified in Umbilical Cord (UC) cell line by semi quantitative-PCR. The internal control β-actin was used to normalize the IRS1, IRS2, GLUT4 gene expression levels. This is the first example of UC cells being induced by a ligand in expressing genes that regulate glucose and insulin levels. Metadichol ® treatment at different concentrations on UC cells showed upregulation of IRS1, IRS2 and GLUT4. 100 pg/mL concentrations showed the highest upregulation of IRS1, IRS2 and GLUT4 expression. 1 ng and 100 ng/mL treatment showed marginal. Metadichol ® is in addition a TNF alpha inhibitor and also inhibits Plasminogen Activation Inhibitor (PAI1) also known as SERPINE1. These genes play an important role in diabetes. The experimental results fully correlated with curated literature data using Bioinformatics software. Network analysis show the uniqueness of shared genes, IRS1, IRS2, GLUT4, TNF, PAI1, acting through multiple pathways that target multiple diseases.
Article
Full-text available
Purpose: Currently, several disorders including burns, trauma, excisional and diabetic wounds, and bedsores threaten the human health. Application of mesenchymal stem cells (MSCs) is recommended for treatment of skin disorders. However, because of oxidative stress and inflammation after skin injury, survival of transplanted MSCs is low which in turn negatively affects the efficiency of the MSCs-based therapy. In an attempt to address the aforementioned challenge and introducing a novel potential therapeutic strategy, we employed combination therapy by Lipocalin (Lcn2)-engineered MSCs and a Metadichol (an inverse agonist of vitamin D receptor (VDR)) nanogel in a rat model of excisional wound. Methods: First, Human umbilical cord MSCs (hUC-MSCs) was transfected by a recombinant plasmid encoding Lipocalin 2 (Lcn2) gene. Next, a combination of Metadichol nanogel and the engineered MSCs was co-applied on wound in rat model of excision injury. Finally the improvement of wound healing in experimental groups was evaluated by photography and histological assessments (hematoxylin and eosin staining). Results: Our findings revealed that the repair rate was higher in the group received combination therapy comparing to control groups. Notably, Metadichol+Lcn2-MSCs showed significantly higher wound contraction rate compared to control group at all time points (p value< 0.001). Furthermore, wound repair rate was 95% 14 days after surgery, and 100% after 21 days in the treatment groups. Our results also revealed that the combination therapy improved and accelerated the wound healing process. Conclusion: Our findings suggest a novel potential therapeutic strategy i.e. Lcn2-engineered MSCs and Metadichol for wound healing. However, further preclinical and clinical studies are required.
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Psoriasis affects 3% of the population worldwide, and there is no known cure. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, and Crohn’s disease. Psoriasis treatments today include steroid and vitamin D3 cream, ultraviolet light, and immune systemsuppressing medications such as methotrexate. The T cells responsible for psoriasis are Th1 and Th l7 cells. IL-22, produced by Th17 cells, is crucial for the proliferation of keratinocytes. IL-22 with the help of IL-17 can induce the critical events of psoriasis. To maintain Th17 cells, IL-23 is required, and it is released from tumor necrosis factor-alpha (TNF-alpha) induced pathways. The pathophysiology of psoriasis involves RORC (retinoic acid receptor-related orphan nuclear receptor gamma) as a critical transcription factor for the development of Th17 cells. FDA has approved an antibody Secukinumab® targeting TNF-α for the treatment of psoriasis. Other FDA approved drugs are Tremfya® targeting IL23 for treatment of moderate to severe plaque psoriasis and Taltz® that blocks IL17 for treatment of plaque psoriasis. Metadichol® a nanoformulation of long-chain lipid alcohols derived from food is a TNF-alpha inhibitor and also binds to Vitamin D receptor (VDR) that could have beneficial effects on Psoriasis. VDR modulates Th1-mediated inflammatory disease like psoriasis. We now present evidence that Metadichol is an inverse agonist of RORγt and AHR (Aryl Hydrocarbon Receptor) thus controlling Th17, IL17 and IL22. Being a TNF-alpha inhibitor, it can control IL23 thus blocking the significant pathways that exacerbate psoriasis. We present case studies of 7 patients afflicted with psoriasis and skin related conditions and how treatment with Metadichol resolved the underlying disease. Metadichol® has properties that allow its use as a safe nontoxic solution to combating the growing number of psoriasis cases
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We recently reported that Metadichol ® [1] brings about a three to four-fold increase in Vitamin C levels in patients without the use of Vitamin C supplementation. In this study of 6 patients who experienced a 5-12 fold increase in plasma Vitamin C levels higher than 80-100 u mol/L level which is the highest reported to date by oral supplementation at high doses of Vitamin C. Metadichol improved in these patients TSH levels, normalized High Blood pressure, fasting glucose levels, reduced eosinophil count, high triglycerides, body fat reduction and increased bone mass, normalized sodium levels, reducing high insulin levels, increased creatinine output in urine and also reducing of Red Cell Distribution width %. Metadichol thus serves as a surrogate for Vitamin C at doses of 5 mg per day as opposed to mega doses that are currently used.
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Vitamin C, also known as ascorbic acid, is a water-soluble antioxidant. Today we meet our requirements of vitamin C through consumption of fruits and vegetables or by supplementation. Homo sapiens cannot produce vitamin C like many other species that can convert glucose to vitamin C. The gene for enzyme production is dormant in humans. The gene, GULO, that we all carry converts glucose to Vitamin C. in other species but not in humans and primates. The open-label study showed Metadichol ® raised levels of vitamin C by 3 fold, endogenously without supplementation of Vitamin C. Possible mechanisms for the increased Vitamin C levels through antioxidant pathways are presented. Metadichol ® [1] is a nano-formulation of long chain alcohols derived from sugar cane. In addition to increased Vitamin C levels reduction in Potassium and uric acid, and decreased blood pressure and improvement in quality of life issues were also observed.
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Metadichol® is a Nanoemulsion of long-chain alcohols found in many foods. Metadichol acts as an inverse ag-onist on Nuclear Vitamin D receptors (VDR) that have a ubiquitous presence in cells and acts by modulating the immune system and affects many biological processes to modulate many diseases. We have demonstrated that Metadichol is useful in both type 1 and two diabetes and in modulating insulin levels and reducing sugar levels and thus increasing insulin sensitivity. We had earlier shown that it binds to VDR and thus an effect on glucose homeostasis that is a hallmark of VDR pathways. We now report also that it is an agonist of GPR120 (G protein-coupled receptor 120) which has emerged as a key target for metabolic diseases like obesity and insulin resistance. In the in-vitro assay, Metadichol is comparable to GW9508 the most extensively used standard compound in GPR 120 research.
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A b stract Metadichol® [1] is a Nanoemulsion of long-chain alcohols called as Policosanol and is present in foods such as rice, sugar cane, wheat, and peanuts. Metadichol® acts on Nuclear Vitamin D receptors (VDR) that have a ubiquitous presence in cells and tissues of the body to stimulate the immune system and inhibit a variety of disease processes, resulting from viral, bacterial and parasitic infections. Infectious agents can cause disease by avoiding normal host defense mechanisms or by subverting them to promote their replication. They do so by blocking VDR receptor that is responsible for innate immunity, and this suppression of the immune response leads to persistent infections. We present a case study of a patient who had acquired MRSA infections and how Metadichol® by its actions on the VDR has resolved the problem of this deadly disease without any side effects.
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The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across often-conflicting sources, providing effective annotation consolidation. A central feature is a balanced Genes section, with scores reflecting the strength of disease-gene associations. This is accompanied by other gene-related disease information such as pathways, mouse phenotypes and GO-terms, stemming from MalaCards' affiliation with the GeneCards Suite of databases. MalaCards' capacity to inter-link information from complementary sources, along with its elaborate search function, relational database infrastructure and convenient data dumps, allows it to tackle its rich disease annotation landscape, and facilitates systems analyses and genome sequence interpretation. MalaCards adopts a 'flat' disease-card approach, but each card is mapped to popular hierarchical ontologies (e.g. International Classification of Diseases, Human Phenotype Ontology and Unified Medical Language System) and also contains information about multi-level relations among diseases, thereby providing an optimal tool for disease representation and scrutiny.
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Background Metadichol (1,2) is a Nano emulsion of long-chain alcohols called policosanols which are found in many foods like rice, wheat, grapes, sugar cane, apple and many others (3). It acts on membrane receptors in cells throughout the body to stimulate the immune system and inhibit a variety of disease processes, including those that result in metabolic diseases such as diabetes, obesity and hypertension. Methods A 38-year-old male of middle eastern origin was diagnosed as diabetic after complaining of tiredness and bouts of hunger. He was not on any medication and chose to be treated with Metadichol @ 10 mg per day. Findings Metadichol helped to lower his fasting blood sugar level from 300 mg/dl to normal in 6 weeks. His HBA1C was reduced from 9.8% to 6.2% in 12 weeks. After 32 more months, his diabetic indicators remain normal. Interpretation Metadichol is safe and effective in controlling blood sugar and HbA1C levels in humans. Metadichol has been shown to bind to the vitamin D receptor (2) as an inverse agonist. However, it acts more like a protean agonist ligand (4) to increase or decrease activity depending on the system. Since Metadichol has no known negative side effects and consists of natural components of common foods, Metadichol has the potential to serve as a novel treatment for type 2 diabetes.
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Background: The development of methods for improving skin wound healing may have an impact on the outcomes of a number of medical conditions. The topical use of polyunsaturated fatty acids (PUFAs) can accelerate skin wound healing through mechanisms that involve, at least in part, the modulation of inflammatory activity. Purpose: We evaluated whether G-protein-coupled receptor 120 (GPR120), a recently identified receptor for docosahexaenoic acid (DHA) with anti-inflammatory activity, is expressed in the skin and responds to topical DHA. Method: Male Wistar rats were submitted to an 8.0-mm wound on the back and were immediately administered a topical treatment of a solution containing 30 μM of DHA once a day. The healing process was photodocumented, and tissues were collected on Days 5, 9, and 15 for protein and RNA analyses and histological evaluation. Results: GPR120 was expressed in the intact skin and in the wound. Keratinocytes expressed the most skin GPR120, while virtually no expression was detected in fibroblasts. Upon DHA topical treatment, wound healing was significantly accelerated and was accompanied by the molecular activation of GPR120, as determined by its association with β-arrestin-2. In addition, DHA promoted a reduction in the expression of interleukin (IL) 1β and an increase in the expression of IL-6. Furthermore, there was a significant increase in expression of transforming growth factor β (TGF-β) and the keratinocyte marker involucrin. Discussion: Topical DHA improved skin wound healing. The activation of GPR120 is potentially involved in this process.
Article
Objective: This study was conducted to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). Methods: This randomized, double-blind, placebo-controlled trial was performed among 60 patients with grade 3 DFU according to "Wagner-Meggitt's" criteria. Participants were randomly divided into two groups (each 30 participants) and received either 50,000IU vitamin D supplements every 2weeks for 12weeks (group A) or placebo (group B). Fasting blood samples were taken at study baseline and after 12-week intervention to determine related markers. Results: After 12weeks of intervention, compared with the placebo, vitamin D supplementation resulted in a significant reduction in ulcer length (-2.1±1.1 vs. -1.1±1.1cm, P=0.001), width (-2.0±1.2 vs. -1.1±1.0cm, P=0.02) and depth (-1.0±0.5 vs. -0.5±0.5cm, P<0.001), and erythema rate (100% vs. 80%, P=0.01). In addition, in supplemented patients changes in serum insulin concentration (-3.4±9.2 vs. +2.8±9.3 μIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-1.5±4.1 vs. +1.7±5.1, P=0.01), the quantitative insulin sensitivity check index (+0.006±0.02 vs. -0.006±0.02, P=0.03) and HbA1c (-0.6±0.6 vs. -0.1±0.5%, P=0.004) were significantly different from those of patients in the placebo group. Additionally, following supplementation with vitamin D, significant reductions in serum total- (-15.8±18.9 vs. +5.3±31.8mg/dL, P=0.003), LDL- (-17.2±19.8 vs. +2.2±28.6mg/dL, P=0.003), total-/HDL-cholesterol ratio (-1.1±0.8 vs. -0.2±1.1, P=0.001), high sensitivity C-reactive protein (hs-CRP) (-0.4±2.5 vs. +1.9±4.2μg/mL, P=0.01), erythrocyte sedimentation rate (ESR) (-34.7±32.4 vs. -18.0±26.6mm/h, P=0.03) and plasma malondialdehyde (MDA) concentrations (-0.7±0.9 vs. -0.2±0.5μmol/L, P=0.008) were seen compared with the placebo. Conclusions: Overall, vitamin D supplementation for 12weeks among patients with DFU had beneficial effects on glucose homeostasis, total-, LDL-, total-/HDL-cholesterol, ESR, hs-CRP and MDA levels. In addition, vitamin D may have played an indirect role in wound healing due to its effect on improved glycemic control.