Tag Archives: Skin Inflammation

Epithelial Barrier Dysfunction in Noncommunicable and Communicable Diseases

The modern world’s dramatic increase in the number and types of chemicals in which man is exposed, a major part of of someone’s exposome, responsible for about 90% of diseases (not genetics), is causing a dramatic rise in noncommunicable and communicable diseases. Over 350 000 chemicals and mixtures of chemicals have been registered for production and use, up to three times as many as previously estimated, and an underestimate of the true number of chemical types that have been produced and commercialized. As the skin and other epithelial tissues are compromised and exposed to communicable diseases, skin and epithelial transmitted diseases are on the rise. For example, the shingles virus can enter through the skin or the epithelial tissue in our respiratory tract, and having shingles can even lead to increased risk of dementia (2nd Ref). Further, a compromised skin epithelial barrier caused by environmental factors such as mechanical trauma, exposure to exogenous proteases in microorganisms and our food, detergents, and air pollution can activate the innate and adaptive immune systems, inducing keratinocytes to release pro-inflammatory cytokines and chemokines and enhancing the antigen presentation by intradermal Langerhans cells (LCs) and dermal DCs and activating T-cells. In turn, for example, activation of T2 type T-cells leads to IL-4, IL-5, and IL-13 secretion, provoking skin barrier alteration, immune cell infiltration into skin, and itch as observed in atopic dermatitis. 

The first essential step to skin immunity is the epithelial barrier, as infection and resulting inflammation are impossible without first breaching it. Epithelia, coated with a sugary glycocalyx, not only comprise our skin but also the mucosal membranes that line our organs. Their ability to secrete squalene, mucus, lipids, and antimicrobials help protect against pathogen invasion. Additionally, epithelia can prevent inflammation by physically shoving out cells infested with toxins, allergens, antigens, pathogens, or other damage by seamlessly extruding them. This is a strategy employed by not only epithelia, but also our hair does the same as it sheds. Given that chronic inflammation could stem from a defective epithelial barrier, the current approach of treating only the inflammation will only partially mitigate symptoms of a more central problem, ongoing wound healing and disrupted barrier.

Scientists now understand that in patients with allergic disease, regardless of tissue location, the homeostatic balance of the epithelial tissue barrier is skewed toward loss of differentiation, reduced junctional integrity, and impaired innate defense and a hyperactive adaptive (trained immunity) immune system. Importantly, epithelial dysfunction characterized by these traits appears to pre-date a predisposition to immunological responses against a range of antigens or allergens, and development of allergic disease.

From the disease perspective, trained immunity is beneficial, as it improves the host’s defense against subsequent infection from pathogens. However, it can also be detrimental and result in overly active immune responses or chronic inflammation.  Even the innate immune system has some memory, given evidence that components in House Dust Mite extract activate and likely train macrophages to produce high amounts of CCL17, IL-6, and cysteinyl leukotrienes following re-exposure to HDM through the TNF-α and PGE2 pathways. Thus, an activated immune system, one that has memory and is primed to react, can lead to sensitivities that may be triggered by an overabundance of chemicals in the environment, and those sensitivities heightened by a disrupted barrier.

Evidence that epithelial barrier dysfunction explains the growing prevalence and exacerbations of inflammatory diseases such as eczema has grown through many studies performed world-wide. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s that cannot be accounted soley by the emergence of improved diagnostic methods. They are indeed increasing in prevalence, i.e. the number of afflictions per 1,000 people.

Eepithelial barrier dysfunction enables the microbiome’s translocation from the skin’s surface to interepithelial and deeper subepithelial areas, doing in combination with allergens, toxins, pathogens, and pollutants. Thereafter, microbial dysbiosis and possible infection, characterized by colonization of opportunistic pathogenic bacteria and loss of the number and biodiversity of commensal bacteria results. Local inflammation, impaired tissue regeneration, and remodeling characterize the skin that suffers from impaired barrier. For example, commensal bacteria on the skin’s surface are important for epidermal lipid synthesis and improve barrier function. The skin’s microbiome is therefore critical to maintaining epidermal barrier function. The infiltration of inflammatory cells and inflammatory cytokines to affected tissues is part of the immune system’s response to erradicate invading bacteria, allergens, toxins, and pollutants away from the deep tissues. As Peter Elias, M.D. has written, “AD [atopic dermatitis] can be considered a disease of primary barrier failure, characterized by both a defective permeability (Proksch et al., 2006, and references therein) and antimicrobial function.” Further, inflammatory cells and inflammatory cytokines that migrate from the skin to other organs may play roles in the exacerbation of various inflammatory diseases in other organs. Thus, inflammation iniated in the skin may contribute to chronic inflammatory diseases in other tissues.

What Dr. Elias has been saying is that the permeability-barrier abnormality in AD is not merely an epiphenomenon but rather the “driver” of disease activity, an “outside–inside view of disease pathogenesis” (Elias and Feingold, 2001). The evidence for this is: (1) the extent of the permeability-barrier abnormality parallels severity of disease phenotype in AD, (2) both clinically uninvolved skin sites and skin cleared of inflammation for as long as 5 years continue to display significant barrier abnormalities, (3) topical artificial barrier therapy comprises effective ancillary therapy, and (4) specific replacement therapy, which targets the prominent lipid abnormalities that account for the barrier abnormality in AD, not only corrects the permeability-barrier abnormality but also comprises effective anti-inflammatory therapy for AD (Figure 1; Chamlin et al., 2002). Thus, inflammation in AD may begin with insults from without, i.e. the exposome.

That barrier insult can then activate epithelial cells in the skin, keratinocyes, which are non-professional immune cells, but do possess MHC-II molecules, that present antigens to professional immune cells, such as T-cells. Thus, with disrupted barriier, the keratinocytes can recognize antigens and present them to the immune system, leading to inflammation. More and more, scientists are discovering how epithelial cells are part of the immune system, regardless in which organ they exist. Key here is to protect barrier function in all of our epithelial tissues, including the skin.

So if inflammatory diseases such as eczema and psoriasis are environmentally triggered and lead to barrier dysfunction and resultant inflammation, what can we do?

First, calm the inflammation. It’s destructive and further degrades the epidermal barrier. S2RM technology (in NeoGenesis Recovery) is great for reducing inflammation, doing so in both the innate and adaptive immune systems.

Second, use a topical product that provides the 3 lipids and natural moisturizing factors that are needed to rebuild normal stratum corneum and barrier function. One product to use is NeoGenesis Barrier Renewal Cream (BRC).

Third, use a product that provides instantaneous barrier function and commensal bacteria. The instantaneous barrier allows the BRC to rebuld the natural barrier function over time, and the commensal bacteria help to rebuild the barrier through activation of lipid synthesis by skin cells. The commensal bacteria in Neogenesis MB-2 also help to reduce the Staphylococcus aureus infection often assicated with disrupted barrier function.

So remember, these inflammatory skin conditions are triggered by the environment. Therefore, their treatment and prevention means that if you change your environment, you can prevent or treat these diseases. Part of changing your environment is the careful choice of topical products to reduce inflammation and renormalize the structure and function of your skin.

Human Platelet Extract: Some People Want You to Apply Blood Clotting, Cancer-Causing Factors to Your Face

In the land of where some people will do nearly anything for money, a company is selling “human platelet extract” as a topical cosmetic product for daily use on normal skin. Can you say, “Gee, let’s clot our skin’s blood supply, induce inflammation, and induce cancer at the same time?” Yes, extended use of a platelet extract product is likely carcinogenic (Carr et al, 2014; Sabrkhany et al, 2021).  To be clear, platelet lysate (extract) triggers an inflammatory response in stem cells in the skin and induces the secretion of factors maintaining immune cells (macrophages) in a proinflammatory state thus enhancing inflammation (Ulivi et al, 2014), and long term inflammation is dangerous.

First, platelet extract does not contain exosomes as some are claiming. The company Plated uses the term “Renewosome”” to fool people. It’s marketing hype that the hysterical mass media has been repeating. They even put a trademark after this silly name. Lol. Platelet-derived exosomes (PLT-Exos) are the main subtype of extracellular vesicles secreted by platelets, which carry proteins, nucleotides, lipids, and other substances to acceptor cells, playing an important role in intercellular communication.” Notice the term “secreted.” Exosomes are actively secreted from living platelets, and an extraction process of platelets will not yield any exosomes. None. I introduced the concept of and actual products containing exosomes to skin care over a decade ago. Many people criticized me at the time, and never bothered to read my peer-reviewed work on the subject, including my scientific book on the subject. But over a decade later following my introduction of exosomes to skin care, the word is out and people are making false claims to have exosomes in their products. Again, exosomes must be released (secreted) and cannot be collected through cellular extraction processes.

BTW, if you want to buy some human platelet extract (lysate is the scientific term for extract), here’s the source:

You can also purchase the platelet extract without fibrinogen. The company has removed the fibrinogen to reduce clotting because fibrinogen is one of the clotting factors.

So, what are platelets? Platelets are anucleated red blood cells that circulate in blood. They are small because they’re anucleated and can therefore squeeze into small places. Platelets are called into action when a wound occurs and blood is spewing. Their job is to close the wound fast by clotting to stop blood leakage, and by inducing high rates of cellular proliferation and inducing an inflammatory response to fight infection. Thus, quoting from Scherlinger et al (2023) in a Nature review article, “platelets produce soluble factors and directly interact with immune cells, thereby promoting an inflammatory phenotype. Furthermore, platelets participate in tissue injury and promote abnormal tissue healing, leading to fibrosis.” Inflammation, fibrosis, abnormal tissue healing with an abnormal matrix, and proliferation are hallmarks of cancer. Tumors are wounds that don’t heal, and applying platelet extract on your face mimics a wound that doesn’t heal. Platelets don’t live long in humans, about 7-10 days, nor would you want them to. They’ve evolved to flux into an area rapidly, secrete all of their inflammatory, clotting, and proliferative factors, close the wound, and then die before before they cause too much damage. If the platelets didn’t die, but instead stayed around for a long time secreting their inflammatory, clotting, and proliferative factors, it would be similar to applying platelet extract to your skin on daily basis. Chronic inflammation, clotting and fibrosis with tumorigenesis would result.

If we consider platelet rich plasma (PRP), a less concentrated form of platelet extract, an inflammatory response in fibroblasts is induced that leads to the formation of ROS (reactive oxygen species) and activation of oxidative stress pathways. It does not promote regeneration. Recent studies have found, “Treatment with PRP increased reticular dermis thickness with a fibrotic aspect. In the long term, the presence of inflammation and microangiopathy caused by PRP injection could lead to trophic alteration of the skin and the precocious aging process.” In other words, platelets cause fibrosis and advanced aging of the skin. Why someone would want to use platelet extract on their skin is beyond me.

According to epidemiologists, “A growing body of laboratory research has shown the direct involvement of platelets with cancer.: Cancer follows a high platelet count. Signaling by platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial–mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. In other words, the extract of platelets will be high in PDGF and when applied daily will enhance the probability of cancer.

Recent studies have found that over-active PDGF signaling is implicated in several types of human malignancies, in one way by promoting proliferation, survival and invasion of tumour cells directly, and in another way by changing the tumor stroma (matrix) in a manner that promotes tumorigenesis. If we look at a product called Regranex, which is a topical product containing 0.01% PDGF, the label includes a warning, “Malignancies distant from the site of application have occurred in REGRANEX users in a clinical study and in postmarketing use.” Thus, using a platelet extract, loaded with PDGF, on a daily basis may be asking for trouble, specifically tumorigenesis.

Let’s look at the ingredients of the platelet extract product used in a “clinical study” of the platelet extract product (from their website):

“purified water, glycerin, pentylene glycol, trideceth-9, panthenol, human platelet extract™, PEG-5 isononanoate, polyacrylate crosspolymer-6, hyaluronic acid, caprylyl glycol, 1,2-hexanediol, hydrolyzed gelatin, arginine, silanetriol, saccharide isomerate, menthyl lactate, carnosine, citric acid, sodium citrate.”

Question – If the “human platelet extract” is so good, why do they need to include all of those other actives?

Answer- because the platelet extract doesn’t work well on its own. At NeoGenesis, we don’t have to add anything to our S2RM adult stem cell-based technology containing exosomes because it really works.

Let’s look at a study published by the company selling platelet extract. The study is:

This study is for short term results in treated skin, not long term results in normal skin. The study suffers from a poor experimental design, conflicts of interest, and the results are underwhelming,

First, the study was not conducted at Mayo Clinic as some people have said in social media. Rather the study was performed for payment from the company to a plastic surgeon named Steve Dyan, and the authors included those employed by the company. So Steve Dyan put his name on the paper for money – this is common, and is called ghostwriting. This is where a physician puts their name on a paper when others have done the work. He was paid to put his name on this published paper. This is a conflict of interest, and is one of the reasons why most medical research and clinical trials cannot be believed.

Look at the study design, and find the problem with the design:

Treatment Group – Before Procedure:   “A 7-day pre-procedure facial skincare regimen for subjects randomized to the HPE treatment group included Cetaphil cleanser (or equivalent) twice daily morning and evening, with application of HPE once daily, and EltaMD (Colgate-Palmolive, New York, NY) UV Daily Broad-Spectrum SPF 40 (or equivalent) in the morning, with reapplication throughout the day as needed.”
Treatment Group – Post-Procedure: 

 “Post-procedure skincare (until the skin was fully healed at 7–10 days) in the treatment group included application of HPE three times daily (morning, mid-day, and before bedtime) followed by Vanicream (PSI, Rochester, MN) Moisturizing Ointment as needed for dryness, applied 15 min after HPE CALM. Post-healing when were they [sic] determined “healed” skincare in the HPE treatment group included Cetaphil (Galderma, Fort Worth, TX) cleanser twice daily, application of HPE three times daily, sunblock, and Vanicream.” 

Control Group: “Post-procedure skincare in the control group (until the skin was fully healed) included application of silicone gel twice daily and application of Vanicream Moisturizing Ointment as needed for dryness. After complete healing, the control group used Cetaphil cleanser twice daily and application of sunblock.”

Do you see the problems?

A proper study design will make the control and experimental groups the same except for the one variable, which is the test product.


Did the study do this?

No, the treatment group received extra care in the form of 7-day pre-procedure care.


Are the results convincing?

No, look at the pictures and the data – the improvement is minimal if at all.


Why didn’t the study use an active comparator?
Basically this is a study of platelet extract versus doing nothing. A good study would have compared the platelet extract to something that is known to improve post-procedure healing, something like, say, NeoGenesis Recovery. The company decided to compare their product to doing nothing, and even when compared to doing nothing, the results are poor.

I could have formulated a product using platelet extract years ago, but decided not to because it is not good for the skin (inflammation and fibrosis) and is dangerous (tumorigenesis). So, if you want clotted blood vessels in your skin, tumorigenesis, fibrosis, and inflammation, go ahead and do as some company wants you to do, apply platelet extract to your face daily. Halloween is coming in a couple of months, and if you start now, you won’t need a costume.