Nonlinear optical microscopy for skin in vivo:Basics,development and applications

Multi-photon microscopy(MPM)and coherent anti-Stokes Raman scattering(CARS)are two advanced nonlinear optical imaging techniques,which provide complementary information and have great potential in combination for noninvasive in vrito biomedical applications.This paper provides a detailed discussion of the basics,development and applications of these technologies for in vrivo skin research,covering the following topics:The principle and advantage of MPM and CARS,instrumentation development for in vino applications,MPM and CARS of normal skin,application of MPM and CARS in skin cancer and disease diagnosis;application of MPM in skin disease intervention,ie.,imaging guided two-photon photothermolysis.

Topical Application of Synbiotic Bacillus Preparations Positively Affects Skin (Micro) Biology

Alteration in skin microbiome profile is involved in many skin conditions, therefore, microbiome modulation is a reasonable target for skin health. Probiotic skincare was suggested, and leave-on synbiotic skincare preparation, blending bacillus spores, as probiotic active ingredient, and inulin sugar, as prebiotic booster, is evaluated, using microarray, 16S gene sequencing, and clinical skin analyses. Topical application of leave-on synbiotic skincare on skin model activates a profound effect on skin biology, expressed in the transcriptome level, with higher than 10% affected genes. The significance of the synbiotic preparation on skin biology was assured, indicating the involvement of major biological pathways. Blending probiotic with Polygonum aviculare plant extract, had triggered a distinct gene expression alteration, demonstrating the sensitivity of skin responses to different active substances. A synbiotic skincare application, had successfully introduced live and active Bacillus probiotics on human skin, detectable days after application was finalized. Following synbiotic application, the microbial content of several microorganisms, related to skin pathologies, was reduced, while the content of bacillus species, representing a healthier microbiome status, was increased, suggesting that frequent application may lead to overall healthier skin microbiome. Acne vulgaris involves unbalanced skin microbiome, with expansion of Cutibacterium acnes. The efficacy of a synbiotic skin cream was assessed to improve acne symptoms, including IGA dermatologist acne severity score, the number of counted acne lesions, measured skin oiliness and skin redness, visual appearance of skin-pores, skin smoothness and softness, and Acne Quality of Life Index.

Progress in construction and application of skin tissue engineering

Tissue engineering is an interdisciplinary field of bioengineering,cell biology,and biomaterials that seeks to create functional tissues for therapeutic purposes.It is a rapidly growing field of regenerative medicine that has the potential to revolutionize the treatment for many diseases and injuries.General research areas mainly include the engineering of the cardiovascular system,bone and cartilage,oral cavity and skin,and other tissues[1].Skin tissue engineering is one of the earliest clinically applied,most mature and widely used products in the field of tissue engineering[2].

Atopic eczema treatment now and in the future:Targeting the skin barrier and key immune mechanisms in human skin

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin(IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

Development of a Freeze-Dried Skin Care Product Composed of Hyaluronic Acid and Poly(γ-Glutamic Acid) Containing Bioactive Components for Application after Chemical Peels

Eight types of spongy sheet were prepared by freeze-drying aqueous solutions of hyaluronic acid (HA) and poly(γ-glutamic acid) (PGA) with or without bioactive components including vitamin C derivative (VC), glucosylceramide (GC), and epidermal growth factor (EGF). Spongy sheets were categorized into the following groups: Group I (HA/PGA), Group II (HA/PGA + VC), Group III (HA/PGA + GC), Group IV (HA/PGA + VC, GC), Group V (HA/PGA + EGF), Group VI (HA/PGA + VC, EGF), Group VII (HA/PGA + GC, EGF), and Group VIII (HA/PGA + VC, GC, EGF). In the first experiment, we examined fibroblast proliferation in conditioned medium that had been prepared by immersing each spongy sheet in a conventional culture medium. EGF-incorporating spongy sheets (Groups V-VIII) enhanced fibroblast proliferation more than EGF-free spongy sheets (Groups I-IV). In the second experiment, cytokine production by fibroblasts was evaluated using a wound surface model. This involved elevation of fibroblasts-incorporating collagen gel sheets to the air-liquid interface, on which a spongy sheet (Groups I, IV, V and VIII) was placed and cultured for 1 week. EGF-incorporating spongy sheets (Groups V and VIII) enhanced the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by fibroblasts more than EGF-free spongy sheets (Groups I and IV). The effect of these four types of spongy sheet on wounds was investigated in animal experiments. Chemical peel was performed by contacting 50% trichloroacetic acid (TCA) on the dorsal region of mice, after which a spongy sheet was placed, and the wound condition was then observed in a two-week period. Angiogenesis was facilitated to a greater degree in Group VIII compared with Groups I, IV and V. This finding indicates that Group VIII spongy sheet is a promising aid for skin recovery after chemical peel.

Tissue-Engineered Products for Skin Regenerative Medicine

In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer.

Dynamic mechanical allodynia following finger amputation:Unexpected skin hyperinnervation

The development of chronic pain after amputations is not an uncommon event. In some cases the most disabling problem is represented by the symptom called dynamic mechanical allodynia, characterized by the painful sensation evoked by gently stroking the skin. Despite the growing interest in understanding pain mechanisms, little is known about the mechanism sustaining this peculiar type of pain. We present here the case of a 53-year-old female patient who complained of severe tactile allodynia in the hand after amputation of her left second finger, resistant to several medical and surgical treatments. In order to gain information about the pain mechanism, two neurodiagnostic skin biopsies were obtained from the area of tactile allodynia and from the contralateral, normal skin area. Skin biopsies showed an unexpected increased innervation of the allodynic skin compared to the contralateral, normal skin area(+ 80.1%). Hyperinnervation has been proposed as a mechanism of pain following nerve lesions, but the increased innervation described here could be also attributed to neuronal plasticity occurring in chronic inflammatory conditions. Independently from the uncertain cause of the epidermal hyperinnervation, in this patient we tried to reduce the elevated number of epidermal nerve fibres by treating the skin with topical capsaicin(0.075%) three times a day, and obtained a persistent pain relief. In conclusion, neurodiagnostic skin biopsy might represent an useful tool for detecting derangements of epidermal innervation in patients with dynamic mechanical allodynia and can help to select an individually tailored therapeutic strategy in such difficult clinical conditions. Further studies are needed to clarify this issue and try to gain better understanding of chronic pain mechanisms in patients who underwent finger amputation.

Modulation of a Specific Pattern of microRNAs, Including miR-29a, miR-30a and miR-34a, in Cultured Human Skin Fibroblasts, in Response to the Application of a Biofunctional Ingredient that Protects against Cellular Senescence <i>in Vitro</i>

Skin aging is a process of structural and compositional remodeling that can be manifested by wrinkling and sagging. Remarkably, the dermis plays a dominant role in the aging process. Recent studies suggest that microRNAs are implicated in the regulation of gene expression during aging. However, studies about age-related microRNAs and how they modulate skin aging remain limited. In the present work, a complex of hydrolyzed natural yeast proteins (Saccharomyces cerevisiae) and hydrolyzed natural soya bean was developed and showed the ability to modulate the expression of telomere-binding protein TRF2, which is a key factor for telomere protection and to prevent cellular senescence in vitro and DNA damage. The aim of the study was to identify microRNAs specifically modulated after application of the ingredient complex to cultured fibroblasts, and their possible involvement in remodeling of the human extracellular matrix and fibroblast senescence. Consequently, human skin fibroblasts were cultured and treated with 1% of the ingredient complex for 48 h before analyzing microRNA modulation by RT-qPCR. The use of bioinformatics allowed us to predict the target genes for modulated microRNAs. Results show that the ingredient complex modulated a pattern of microRNAs including the down-regulation of miR-29a-3p, miR-30a-5p and miR-34a-5p, which are associated with fibroblast senescence and remodeling of the human dermal extracellular matrix. In conclusion, our results indicate that miR-29a-3p, miR-30a-5p and miR-34a-5p possibly represent key microRNAs that impact human fibroblast senescence and remodeling of the dermal extracellular matrix.

Low Dose Total Skin Electron Beam Radiation in Cutaneous T-Cell Lymphoma: Review

The treatment of advanced stage MF is especially challenging as single agent overall response rates are in the 35% range and chronic recurrence is the rule. The treatment of CTCL across all stages of disease is aimed at the goal of achieving and sustaining remission. Increasingly, low dose total skin electron beam therapy (TSEBT) is being utilized as a skin directed component in combination therapy for advanced stage CTCL. Researchers are seeking to better define the utility of low dose TSEBT as a method of debulking skin disease while simultaneously treating other disease compartments and in combination with sustained maintenance therapies of both the skin directed and systemic varieties. Data exists showing the efficacy of low dose TSEBT in early and advanced disease. There is also data documenting prolonged treatment responses with TSEBT plus adjuvant skin directed therapies such as PUVA and topical nitrogen mustard. Emerging data examining the role of low dose TSEBT in the prestem cell transplant preparation is also promising. This brief review summarizes the utility of low dose TSEBT in multiagent treatment regimens in CTCL.

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

Background: Calotropis procera (C. procera), is an authentic plant naturally grown in the flora of Dead Sea region. Despite its toxicity, C. procera presents healing properties. However, it has not been implemented yet in cosmetics as an active ingredient. Objective: The biological effects of C. procera callus extract on skin were elucidated solely and in combination with Dead Sea water (DSW). Methods: The capability of C. procera extract to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by LPS and SDS addition respectively. Viability and cytokine secretion were evaluated. The combination of C. procera extract with Dead Sea water was tested on full thickness skin equivalents. Gene expression and relevant biochemical markers for glycolysis, hypoxia and extracellular matrix balance were tested. Results: C. procera extract exhibits a protective biological activity against skin irritation and inflammation at the biochemical level. Furthermore, a combination of C. procera extract and DSW demonstrates a potential contribution for skin wellbeing via enhance energy production, resistance to hypoxia and extracellular matrix balance. Conclusions: Topical application of C. procera callus extract might support skin balance and wellbeing at the molecular level. Hence, it is recommended for new cosmetic formulae as standalone or in combination with Dead Sea water, in the effort to achieve anti-aging bio-activity that is working beyond skin aging symptoms, especially via skin calming effects and skin energy enhancement.

Dead Sea Minerals-Induced Positive Stress as an Innovative Resource for Skincare Actives

Objective: Exposure to certain stresses in small doses might lead to a protective effect by improving resistance to other stressors. Dead Sea (DS) minerals can be a relevant source to induce positive stress due to their high salinity and unique mineral combination. This concept could be further optimized using advanced unique cell biotechnology. The purpose of this study was to elucidate the innovative concept of DS minerals (water extract and black mud) supplementation in small amount to Pichia pastoris yeast growth media as a positive stress by testing the capability of accepted fermentation compounds to affect the appearance of skin. Methods: Skin equivalents were topically applied with different Pichia pastoris fermentations (Metabiotics?). Skin elasticity biomarkers were tested, since loss of elasticity and suppleness is a natural skin aging process leading to deeper wrinkles and loss of firmness. A preliminary screening at the gene level using DNA microarray was performed and subsequently, the following proteins were detected using ELISA or immunoblotting assays: elastin, fibulin-1, lysyl oxidase (LOX), metalloproteinase 3 (MMP-3), E-cadherin, claudin 4, tight junction protein (TJP)-1 and TJP-2. UVB irradiation was selected as a stressor. Results: Fermentation compounds generated in the presence of small doses of DS minerals affected the expression of various elasticity-related genes in skin. Moreover, they significantly attenuated the abnormal UVB-induced alterations, the proteins elastin, fibulin-1, LOX, MMP-3, E-cadherin and TJP-2. Conclusions: The observations clearly demonstrate that when DS Metabiotics? compounds are topically applied, significant alterations in several biomarkers that contribute to skin elasticity occur. Thus, these novel compounds have the potential to serve as skincare actives.

Evaluation of Epidermal Growth Factor-Incorporating Skin Care Product in Culture Experiment Using Human Fibroblasts

This study aimed to investigate the potential of a skin care product composed of hyaluronic acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF), vitamin C derivative (VC), glucosylceramide (GC), poly(γ-glutamic acid) (PGA), and argentine (Arg). High-molecular weight HA aqueous solution, hydrolyzed low-molecular weight HA aqueous solution, and heat- denatured Col aqueous solution were mixed, into which each aqueous solution containing EGF, VC, GC, PGA, or Arg were added, followed by freeze-drying to obtain a spongy EGF-incorporating skin care product (EGF-skin care product). In order to evaluate the first efficacy of EGF, fibroblast proliferation was assessed after 6 days of cultivation in the conditioned medium prepared by dissolving EGF-skin care product in a conventional culture medium. The fibroblast densities increased more effectively in conditioned medium with EGF than in control medium without EGF. In order to evaluate the second efficacy of EGF, the amount of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) produced by fibroblasts were assessed in a wound surface model. A fibroblast-incorporating Col gel sheet (cultured dermal substitute: CDS) was elevated to the air- medium interface, onto which a spongy sheet of EGF-skin care product was placed and cultured for 7 days. The condition covered with or without EGF-skin care product is divided into (+) EGF or (-) EGF, respectively. Fibroblasts in the CDS released 3.7 times more VEGF and 25 times more HGF in (+) EGF compared with (-) EGF. In another experiment, an aqueous solution of EGF-skin care product was added onto CDS and cultured for 7 days. Aqueous solutions were prepared and stored at 4°C or 37°C for a different period of 1 day, 2 weeks, and 4 weeks, respectively. Fibroblasts in CDS under different condition released similar amount of VEGF and HGF. This result indicated that the efficacy of EGF was maintained even after preservation at 37°C for 4 weeks. These findings suggest that EGF-skin care product can be used on damaged skin surface by placing its spongy sheet or its solution.

Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy

According to the current definition of neuropathic pain("pain arising as a direct consequence of a lesion or disease affecting the somatosensory system"), the demonstration of a lesion or disease involving the somatosensory system is mandatory for the diagnosis of definite neuropathic pain. Although several methods are currently available for this aim, none is suitable for every type of disease(or lesion). Neurodiagnostic skin biopsy(NSB) is a relatively new technique for the diagnosis of peripheral nerve lesions. It is an objective method, completely independent from the patient's complaining, based on immunohistochemical staining techniques that allow measurement of the density of the epidermal nerve fibers, currently considered the free nerve endings of small diameter(A-delta and C) afferent fibers. NSB has the important property of being used to investigate the skin, allowing obtaining a diagnosis of small fiber axonal neuropathy of peripheral nerves supplying every body part covered by skin. This feature appears to be very important, particularly in cases of unilateral nerve lesions, because it allows going beyond the possibilities of neurophysiological tests which are available only for a limited number of peripheral nerves. All these characteristics make NSB a precious instrument for the diagnosis of peripheral unilateral neuropathic pain.

Safe Retinol-Like Skin Biological Effect by a New Complex, Enriched with Retinol Precursors

Background: Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite its efficacy, the safety profile of RE is controversial. Objectives: Pretinol (PRE) complex was formulated with two RE precursors, β-Carotene and Niacinamide, in order to deliver retinol-like skin benefits with healthier characteristics, assuming that skin enzymes will enable safe RE supply on spot. Methods: The expression levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNFα) and Interleukin 1 alpha (IL-1α), were measured using various skin models before and after exposure to PRE and RE. Full genome microarray was performed and the affected genes and pathways were analyzed. Results: Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated. Skin safety, demonstrated via cytokines expression on ex-vivo skin, results with TNFα and IL-1α elevation by RE application. In contrary PRE significantly reduces TNFα while IL-1α is not affected. These results establish skin safety advantage of PRE vs RE. Microarray results examined on skin equivalents reveal the involvement of PRE in inflammatory attenuation. Conclusions: Formulating RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.

Errors in Surgical Site Identification during Cutaneous Surgery for Skin Cancer: Review and Recommendations

Surgical error due to incorrect identification of the surgical site has been known to occur right from the beginning of surgical practice through the ages. However, increasing awareness, preventative efforts and risks of litigation have not eliminated this problem. Cutaneous surgery for skin cancer makes up a large proportion of procedures performed each year and it is often difficult to correctly identify biopsy sites, especially as this is not easy in sun-damaged skin. In this review article, we review the incidence of wrong-site surgery, measures taken by professional bodies, and the use of photography and newer technologies in an attempt to eliminate this distressing event in the field of plastic and dermatologic surgery. The purpose of this review is to highlight the incidence of such surgical site identification errors, evaluate the risk factors, and educate the surgeon about measures that can be undertaken to avoid being faced with such a situation.

Differences in Skin Properties of Korean Women at the Initial Aging Phase

Many studies on aging have focused on evaluating differences between older and younger people, but only a few have focused on differences in skin properties among subjects from the same age group according to their skin aging status. In this study, we evaluated the facial skin condition and life style factors in 110 Korean women aged 25 to 35 in an attempt to evaluate factors which may affect the skin aging status in the initial aging phase. The facial skin condition of 110 healthy Korean women was assessed over two successive 6-month periods, summer and winter. Using clinical assessments including aging, wrinkles and skin’s elasticity values, the subjects were divided into 7 groups. Then, various facial skin conditions and life style factors were examined between a severe aging group and mild aging group. In the severe aging group, the mean value pH was lower and the mean value of water content was slightly lower than that of women in the mild aging group. Also, the seasonal site variation in water content and sebum secretion level were significantly higher in the severe aging group than in the mild aging group. Topical sunscreen using percentage was not significantly different between the two groups. However, the number of cosmetic subject use was slightly higher in the mild aging group than in the severe aging group. The study suggested that there were several differences in skin characteristics between women in the severe aging group and in the mild aging group at the initial aging phase. Seasonal site variation between cheek and forehead was the most dominant differences. We also considered that life style factors such as cosmetic use could affect skin aging status.

Evaluation of a Barrier Repair Cream Containing Pseudo-Ceramide for Practical Use by Hairdressers with Hand Skin Disorders Due to Daily Exposure to Chemical Irritants

Hairdressers are exposed to numerous skin-damaging factors, such as wet work, skin irritants, and thermal changes. Skin protection is a very important factor for the prevention of occupational skin disorders. Therefore, we evaluated a hand cream that was specially formulated for highly stressed skin with regard to its capability to reduce dry, rough, and scaly skin. The objective of this study was to conduct a controlled use test of a barrier repair cream containing pseudo-ceramide and demonstrate its efficacy for hairdressers with dry, sensitive hands and/or occupational skin disorders. A total of 30 hairdressers (29 females and 1 male, aged 20 - 67) participated in the study. All subjects suffered from dry hands. Subjects applied the test cream on their hands for 28 days (four weeks). For each subject, the skin surface topography of the hands was measured by the Surface Evaluation of Living Skin (SELS) system at day 14 (week 2) and day 28 (week 4). Dryness, scaling, cracking, redness, and itchiness were evaluated and graded by experts at week 2 and week 4, and then compared to baselines. All 30 subjects completed the study. A comparison of the changes from baseline to endpoint revealed a statistically significant reduction in skin roughness, scaling, and volume measured according to SELS. These data were confirmed by photographic documentation. The results were further supported by the expert evaluation. For the symptoms dryness and scaling, improvement could be observed in almost all regions of the hands. In addition, according to subjective assessments of overall hand skin condition and the hand cream, subjects reported clear improvement over time (p value below 0.001) and good efficacy of the product. In this study, the test hand cream showed excellent skin compatibility. Therefore, the hand cream may be effective for hairdressers with dry, sensitive hands and/or occupational skin disorders.

<i>Dunaliella salina</i>and <i>Haloferax volcanii</i>Synergistically Attenuate Skin Cancer <i>in Vitro</i>

Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy, which causes substantial morbidities and mortalities. Although the significant increase in the understanding of skin cancer formation and the development of novel personalized drug regimens have occurred, new treatment options are always of need. The use of natural compounds to alleviate the symptoms or even to prevent and treat cancer has long been proposed. Specifically, the use of marine-based organisms as a source for cancer cure and remedy is being evaluated extensively. The objective of the current study was to assess the ability of the green microalgae Dunaliella salina, the Dead-Sea-derived Haloferax volcanii, and its combinations to treat skin cancer in vitro. The results demonstrate the Dunaliella and Haloferax can reduce sarcoma and basal cell carcinoma cellular growth. Importantly, their combination acts synergistically in a caspase-3 independent manner. Moreover, a synergistic action was found when evaluated sarcoma cell invasion rate, which was completely blocked at pharmacological relevant amounts of the compounds. Collectively, the results demonstrate that the combination of Haloferax volcanii and Dunaliella salina can be used as a new treatment for skin cancer. The specific mechanism of action and further in vivo validation studies are of need.

The Effects of Regional Climate and Aging on Seasonal Variations in Chinese Women’s Skin Characteristics

OBJECTIVES: Skin characteristics change depending on the external environment such as UV, temperature and humidity. But the research how to affect the regional climate, age and seasonal variation on the skin conditions was not well studied. Therefore, we investigated the seasonal variation in the skin by comparing Beijing women and Guangzhou women by age groups. METHODS: 440 healthy Chinese women participated in this study. The skin hydration, sebum secretion, TEWL and skin pH were measured on the cheek front. All the parameters were analyzed in terms of the age, season and region. RESULTS: The skin hydration in Beijing was lower than that in Guangzhou and significantly decreased during winter than summer. The sebum secretion in their 20s and 30s was significantly high in summer in both regions, and this phenomenon was more remarkable in Guangzhou (p CONCLUSIONS: Skin hydration and barrier function decreased more during a cold, dry winter than summer. The barrier dysfunctions such as an increase in TEWL and pH occurred more commonly in old age groups. The greater the differences between summer and winter climates, the greater damage to skin barrier and skin hydration. The sebum secretion was more affected by hot, humid summers. Further, the aged skin was influenced by seasonal variation except for sebum secretion.

Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress—The Case of The Dead Sea Water

Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.