Advancements in non-invasive skin sampling: Clinical conditions characterization via the assessment of skin surface cytokine biomarkers.

The skin is increasingly recognized as a biological active organ interacting with the immune system. Given that the epidermal skin layer actively releases various cytokines, non-invasive skin sampling methods could detect these cytokines, offering insights into clinical conditions. This study aims non-invasively measuring cytokine levels directly from the skin surface to characterize different inflammatory chronic disorders in the adult and elderly population: psoriasis, diabetes type 2, rosacea, chronic kidney disease (CKD) and aging. Cytokines IL-1ß, IL-8 and IL-10 were sampled from healthy subjects and patients aged 18-80 using skin surface wash technique. A well with sterile phosphate-buffered saline solution was placed on the skin for 30 min, and the extracted solution was collected from the well for further cytokine levels analysis using ELISA assay. Results show distinct cytokine profiles in different pathological processes, healthy controls, affected and unaffected areas. Aging was associated with increased IL-1ß, IL-8, and IL-10 levels in skin. In diabetes, IL-1ß and IL-8 levels were elevated in lesional areas, while IL-10 levels were decreased in non-lesional skin. Psoriatic lesions showed elevated levels of IL-1ß and IL-8. Rosacea patients had lower IL-10 levels in both lesional and non-lesional areas. CKD patients exhibited significantly lower IL-10 levels compared to healthy individuals. In conclusion, skin surface wash-derived cytokine profiles could serve as "alert biomarkers" for disease prediction, enabling early detection. Additionally, this method's cost-effectiveness allows pre-screening of molecules in clinical studies and holds potential as a tool for biomarkers and omics analysis, enhancing disorder characterization and disease management.

Cutaneous Nrf2-Keap1 pathway modulation by environmental factors: The Dead Sea area as a test case.

The skin is constantly exposed to exogenous environmental stressors and has to cope with excessive oxidative stress and tissue damage. However, exposure to moderate environmental stressors may be beneficial for the cutaneous tissue and assist in protecting against oxidative damage via the enhanced activation of the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathway. Such moderate stressors can be found in various locations around the globe. In this manuscript, we chose to focus on the Dead Sea (DS) area as a test case to study the effect of moderate stressors on the cutaneous tissue because of the unique combinations of moderate stressors in this area. The exceptional location of the DS at an altitude of -438 meters below sea level (the lowest place on earth) is responsible for its rare accumulation of moderate stressors such as high-water salinity, high atmospheric pressure, and unique solar radiation. In this manuscript, we hypothesized that the unique solar radiation in the DS area generates moderate oxidative stress in the skin leading to the induction of intracellular electrophiles, which in turn can activate the protecting Nrf2-Keap1 pathway. We showed that exposure of human skin organ culture from the same donor to solar radiation at the DS resulted in significant activation of the Nrf2-Keap1 pathway, induction of phase II enzymes, and lower apoptotic activity compared to a nearby location at a higher altitude (Jerusalem +700 m). This remarkable effect of activating the Nrf2 protecting pathway and the importance and characteristics of the solar irradiation at the DS is discussed.

Dead Sea minerals: New findings on skin and the biology beyond.

BACKGROUND: Therapeutic effects of Dead Sea (DS) minerals are well established, and their unique combination is analysed and reported. DS water (DSW) is a key source for DS minerals, and various studies report the capability of DSW to alleviate symptoms of different skin disorders and to contribute to skin maintenance. However, the biological mechanisms beyond reported effects are not fully understood yet. OBJECTIVE: To elucidate the effect of topically applied DSW via the expression of different skin biomarkers related to barrier function, homeostasis, inflammation and irritation. METHODS: In vitro skin equivalents and ex vivo human skin organ culture were used to assess the biological effects of DSW. Epidermal barrier protein expression and DSW ions transdermal penetration were analysed on skin equivalents. ß-endorphin secretion was tested on human skin organ culture. The capability of DSW to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by lipopolysaccharides and sodium dodecyl sulphate addition, respectively. RESULTS: Topical application of DSW encouraged the expression of the barrier-related proteins: filaggrin, involucrin and transglutaminase, while transdermal penetration of calcium ions was not detected. Additionally, DSW application had increased skin secretion of ß-endorphin and attenuated the expression of inflammatory and irritation-related cytokines. CONCLUSIONS: This study reports new findings of DSW effects on skin. Signalling pathway activation is proposed as a key step that may result in a vast range of proven biological activities following skin exposure to DS minerals, and specifically DSW.

Safety evaluation of traces of nickel and chrome in cosmetics: The case of Dead Sea mud.

BACKGROUND: Metal impurities such as nickel and chrome are present in natural ingredients-containing cosmetic products. These traces are unavoidable due to the ubiquitous nature of these elements. Dead Sea mud is a popular natural ingredient of cosmetic products in which nickel and chrome residues are likely to occur. OBJECTIVE: To analyze the potential systemic and local toxicity of Dead Sea mud taking into consideration Dead Sea muds' natural content of nickel and chrome. METHODS: The following endpoints were evaluated: (Regulation No. 1223/20, 21/12/2009) systemic and (SCCS's Notes of Guidance) local toxicity of topical application of Dead Sea mud; health reports during the last five years of commercial marketing of Dead Sea mud. RESULTS AND CONCLUSIONS: Following exposure to Dead Sea mud, MoS (margin of safety) calculations for nickel and chrome indicate no toxicological concern for systemic toxicity. Skin sensitization is also not to be expected by exposure of normal healthy skin to Dead Sea mud. Topical application, however, is not recommended for already nickel-or chrome-sensitized persons. As risk assessment of impurities present in cosmetics may be a difficult exercise, the case of Dead Sea mud is taken here as an example of a natural material that may contain traces of unavoidable metals.

Non-invasive skin biomarkers quantification of psoriasis and atopic dermatitis: cytokines, antioxidants and psoriatic skin auto-fluorescence.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are challenging to treat due to the absence of suitable monitoring procedure and their recurrences. Alteration of skin hydrophilic biomarkers (SHB) and structural elements occur in both disorders and may possess a distinct profile for each clinical condition. OBJECTIVE: To quantify skin cytokines and antioxidants non-invasively in psoriatic and in AD patients and to evaluate skin auto-fluorescence in psoriatic patients. METHODS: A skin wash sampling technique was utilized to detect the expression of SHB on psoriatic and AD patients and healthy controls. Inflammatory cytokine (TNFα, IL-1α and IL-6) levels, total antioxidant scavenging capacity and uric acid content were estimated. Additionally, measurement of the fluorescent emission spectra of tryptophan moieties, collagen cross-links and elastin cross-links were performed on psoriatic patients and healthy controls. RESULTS: Our findings demonstrate significant alterations of the SHB levels among psoriasis, AD and healthy skin. Differences were also observed between lesional and non-lesional areas in patients with psoriasis and AD. Ultra-structural changes were found in psoriatic patients both in lesional and non-lesional areas. CONCLUSION: Employing non-invasive measurements of skin wash sampling and skin auto-fluorescence might serve as complementary analysis for improved diagnosis and treatment of psoriasis and AD. Furthermore, they may serve as an additional monitoring tool for various diseases, in which skin dysfunction is involved.

Noninvasive skin measurements to monitor chronic renal failure pathogenesis.

BACKGROUND/AIMS: Cutaneous manifestations are common in hemodialysis (HD) patients with chronic renal failure (CRF). Associated with uremia, pruritus is a frequently observed symptom in CRF patients and increases with deteriorating renal function. Skin hydrophilic biomarkers (SHB) may be altered in CRF compared to healthy controls. METHODS: A noninvasive skin wash sampling technique to detect the expression of SHB, by measuring their secretion on skin surface, was used on HD patients and healthy controls. Hydrophilic antioxidants such as total antioxidant scavenging capacity (TSC) and uric acid (UA) content, and cytokine inflammatory biomarkers such as TNFα and IL-10 levels were estimated. RESULTS: Our findings demonstrate significant alterations of the SHB level between HD patients and healthy volunteers. Furthermore, such alterations of secreted SHB correlated markedly with detected changes in blood biochemistry and dermatology severity score. CONCLUSION: Skin wash sampling of SHB is a noninvasive technique that distinguishes between HD patients and healthy controls. In HD patients, SHB is associated with biochemical markers in blood and dermatologic symptom severity. This technique is also suggested, as a monitoring tool for diagnosis and treatments of various diseases, in which skin dysfunction is involved.