Increase In Transepidermal Water Loss Research Articles

Oral administration of Jumihaidokuto inhibits UVB-induced skin damage and prostaglandin E2 production in HR-1 hairless mice

This study was conducted to investigate whether and how Jumihaidokuto (JHT), a traditional Chinese medicine, prevents UVB-induced skin damage in male HR-1 hairless mice. JHT has been traditionally prescribed for patients presenting skin disorders with redness and swelling, and, in Japan, it is approved for prescription to patients with acute and/or purulent skin disorders, hives, acute eczema, and athlete’s foot. Considering the traditional use of JHT, we hypothesized that oral administration of JHT might emerge as an effective strategy to prevent UVB-induced skin damage, such as edema and erythema. Here, we pretreated mice with JHT (1000 mg/kg, p.o.) for 3 weeks and then administered a single dose of UVB irradiation (250 mJ/cm2) on the dorsal skin. UVB irradiation increased the erythema index and transepidermal water loss (TEWL) and decreased the skin water content in the epidermis at 72 h post-irradiation. JHT treatment inhibited the increase of TEWL and the loss of water content in the epidermis, but not the elevation of the erythema index. Moreover, administration of JHT suppressed UVB-induced epidermal hyperplasia by blocking the proliferation of keratinocytes and also inhibited irradiation-triggered reduction of collagen fibers and infiltration of immune cells into the dermis. Lastly, administration of JHT suppressed UVB-induced production of proinflammatory mediators, such as prostaglandin E2 and interleukin-1β. These results suggest that JHT prevents UVB-induced skin damage and that the underlying mechanism involves the inhibition of proinflammatory mediators.

Impact of cigarette smoke on physical-chemical and molecular proprieties of human skin in an ex vivo model.

This is a study about the skin ageing exposome, focusing on the effect of cigarette smoke. Human living skin explants (HSE) were exposed to cigarette smoke (CS) of two cigarettes for 2hours using a custom-made exposure chamber, the Pollubox® . Effects on the surface physico-chemistry and molecular properties of the skin were analyzed and reported for the first time. To this end, transcriptomic study followed by immunohistochemistry, MDA (Malondialdehyde Dosage), and surface physio-chemistry data: surface free energy determination, TEWL (Trans Epidermal Water Loss), skin pH and FT-IR (Fourier Transform-Infrared) spectroscopy of the explant were collected from untreated and treated HSE. Results showed a decrease of the total surface free energy of the treated HSE. This decrease reflected higher interactions with polar compounds from the environment and consequently a decrease of the surface hydrophobicity. Additionally, an increase of TEWL and skin pH was observed after treatment. The transcriptomic analysis showed downregulation of mitochondrial genes (PON2-NDUFA4L2-ATP1A1-ALDH2-PRODH) combined with an increase of MDA in CS-treated HSE. CS-induced oxidation of lipids at HSE surface alters the skin barrier: interactions with polar products are enhanced and the lipid chain packing at the surface is modified. Consequently, skin permeability could increase which correlated with repression of CA9 and AQP1 genes. Beside activation of AHR-NRF2 pathway in CS-exposed HSE, our results suggested that mitochondrial functions were strongly impacted and oxidized lipids failed to be eliminated promoting skin barrier alteration. A mitophagy activity was suggested through the confirmation of PINK1 accumulation in the epidermis by immunostaining.

Effects of local forearm skin heating on skin properties

This study investigated impacts of local skin heating on skin properties and tested whether skin changes depended on heat-induced hyperaemia. It was reasoned that heat-induced vasodilation impacts accompanying interstitial fluid changes. Forearm skin was locally heated from a baseline of 35°C to 40-42°C in 30 young adults (15 females, 15 males, 24.9±2.1years) and non-heated in 10 others (5 females, 5 males, 25.2±1.3years. Skin blood flow (SBF) was continuously measured using a laser Doppler method and skin tissue dielectric constant (TDC), stratum corneum capacitance (SCC) and transepidermal water loss (TEWL) were measured before and after maintained heat for 12min. TDC values were determined to effective measurement depths of 1.5mm (TDC15) and 2.5mm (TDC25). Results showed a large heat-induced hyperaemia, with SBF increasing on average 8.8-fold from its baseline of 35°C. Heating also caused significant increases in TDC, SCC and TEWL that, compared to preheating, increased approximately 1.1-fold, 3.1-fold and 4.5-fold. None of these skin changes correlated with the magnitude of the SBF hyperaemic response. Absence of this correlation may indicate that in young healthy adults, increased capillary filtration due to heat-induced arteriolar vasodilation is rapidly accommodated by postcapillary reabsorption, enhanced lymphatic activity and TEWL processes. An alternate explanation is that heating caused increased red cell oscillations that were detected as part of the laser Doppler increase without representing increased capillary flux. The major determinant of the Increases in TDC, SCC and TEWL is likely a consequence of heat-induced eccrine gland activation. Studies of older persons or those with depressed function are warranted.

Skin barrier function after repeated short-term application of alcohol-based hand rub following intervention with water immersion or occlusion.

Alcohol-based hand rub (ABHR) is recommended for hand hygiene, and application on dry skin is generally well tolerated. However, hydration of the skin may lead to increased susceptibility to ABHR. To evaluate if increased skin hydration changes skin barrier response to ABHR, as compared to application on dry skin. Twenty healthy volunteers participated in a 3-day experimental setup. Intervention areas on the forearms were exposed to either water immersion or occlusion followed by repeated exposures to ABHR. Skin barrier function was assessed by measurement of transepidermal water loss (TEWL), electrical conductance, pH, and erythema at baseline and day 3. The area exposed to water immersion preceding ABHR showed a significant increase in TEWL from baseline to day 3 (P = .04), and for the occluded area the same trend was found (P = .11), with an additional decrease in electrical conductance (P = .03). No significant differences were found for the control area. The assessments did not differ significantly between intervention and control sites. Our results indicate that extensive skin hydration may lead to increased susceptibility to ABHR. Further evaluation of this observation is important, since ABHRs are widely used, particularly among health care workers in whom hand eczema is a huge problem.

Dietary immature Citrus unshiu alleviates UVB- induced photoaging by suppressing degradation of basement membrane in hairless mice

Ultraviolet (UV) irradiation induces physiological and morphological skin damage, resulting in skin dryness, wrinkle formation, and loss of elasticity. The basement membrane (BM) has been shown to play crucial roles in binding epidermis to dermis tightly, regulating cell differentiation and proliferation, and signaling protein production. Dietary flavonoids have been revealed to improve the damage caused by UV exposure. Immature Citrus unshiu is known to contain high concentrations of flavonoids such as hesperidin and narirutin. In this study, the effects of immature Citrus unshiu powder (ICP) on photoaged skin were demonstrated using UVB irradiated hairless mice. Oral administration of ICP improved loss of skin hydration and increase of transepidermal water loss. The histological analyses of hairless mice dorsal skin revealed that oral administration of ICP improved UVB-induced overgrowth of epidermal cell, suppressed epidermal cell mortality and BM destruction. Therefore, the administration of ICP could improve photoaging by protecting the tissues around BM.

Antioxidant/stress response in mouse epidermis following exposure to nitrogen mustard

Nitrogen mustard (NM) is a highly reactive bifunctional alkylating agent that induces inflammation, edema and blistering in skin. An important mechanism mediating the action of NM and related mustards is oxidative stress. In these studies a modified murine patch-test model was used to analyze DNA damage and the antioxidant/stress response following NM exposure in isolated epidermis. NM (20 μmol) was applied to glass microfiber filters affixed to a shaved dorsal region of skin of CD-1 mice. NM caused structural damage to the stratum corneum as reflected by increases in transepidermal water loss and skin hydration. This was coordinate with edema, mast cell degranulation and epidermal hyperplasia. Within 3 h of NM exposure, a 4-fold increase in phosphorylated histone H2AX, a marker of DNA double-stranded breaks, and a 25-fold increase in phosphorylated p53, a DNA damage marker, were observed in the epidermis. This was associated with a 40% increase in 8-oxo-2′-deoxyguanosine modified DNA in the epidermis and a 4-fold increase in 4-hydroxynonenal modified epidermal proteins. At 12 h post NM, there was a 3–75 fold increase in epidermal expression of antioxidant/stress proteins including heme oxygenase-1, thioredoxin reductase, superoxide dismutase, glutathione reductase, heat shock protein 27 and cyclooxygenase 2. These data indicate that NM induces early oxidative epidermal injury in mouse skin leading to an antioxidant/stress response. Agents that enhance this response may be useful in mitigating mustard-induced skin injury.

Influence of Buffers of Different pH and Composition on the Murine Skin Barrier, Epidermal Proliferation, Differentiation, and Inflammation

The pH of the skin is tightly regulated by endogenous buffering systems. We examined the influence of buffers of different pH and composition on skin barrier repair, pH, inflammation, and epidermal thickness/proliferation/differentiation. After tape-stripping in hairless mice buffers with pH 4–7 were applied in patch test chambers. After removal of the chambers, skin pH and transepidermal water loss (TEWL) were monitored for 24 h, and biopsies were taken for histology/immunohistology. Hairless mice showed a basal skin pH of about 5.8. Following barrier disruption and application of water, the pH increased by 0.6 units; increase in pH was reduced by the pH 4 glycolate buffer, unchanged by pH 4 citrate and pH 5.5 buffers, and even increased by the pH 7 buffer. pH 5.5, pH 4 citrate, and pH 4 glycolate buffers led to a slight, while the pH 7 buffer led to a significant increase in TEWL after barrier disruption compared to water. The pH 7 buffers led to a significant increase in epidermal thickness/proliferation/differentiation and inflammation after barrier disruption, whereas buffers with pH 4 and 5.5 caused a slight increase. In conclusion, only the pH 4 glycolate buffer significantly reduced the skin barrier disruption-related increase in skin pH. This was accompanied by only slight increase in epidermal thickness and inflammation compared to water. Application of the pH 7 buffer led to a significant increase in the skin pH, TEWL, epidermal thickness, and inflammation. The results are important for the formulation of topical products for effective acidification in pathological skin conditions.

Severe Skin Permeability Barrier Dysfunction in Knockout Mice Deficient in a Fatty Acid ω-Hydroxylase Crucial to Acylceramide Production

The skin permeability barrier is indispensable for maintaining water inside the body and preventing the invasion of pathogens and allergens; abnormalities lead to skin disorders such as atopic dermatitis and ichthyosis. Acylceramide is an essential lipid for skin barrier formation, and CYP4F22 is a fatty acid ω-hydroxylase involved in its synthesis. Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis, although the symptoms vary among mutation sites and types. Here, we generated knockout mice deficient in Cyp4f39, the mouse ortholog of human CYP4F22, to investigate the effects of completely abrogating the function of the fatty acid ω-hydroxylase involved in acylceramide production on skin barrier formation. Cyp4f39 knockout mice died within 8 hours of birth. Large increases in transepidermal water loss and penetration of a dye from outside the body were observed, indicating severe skin barrier dysfunction. Histologic analyses of the epidermis revealed impairment of lipid lamella formation, accumulation of corneodesmosomes in the stratum corneum, and persistence of periderm. In addition, lipid analyses by mass spectrometry showed almost complete loss of acylceramide and its precursor ω-hydroxy ceramide. In conclusion, our findings provide clues to the molecular mechanisms of skin barrier abnormalities and the pathogenesis of ichthyosis caused by Cyp4f39 and CYP4F22 by association.

Direct assessment of skin epithelial barrier by electrical impedance spectroscopy.

Many skin and mucosal inflammatory disorders, such as atopic dermatitis, have been associated with an impaired epithelial barrier function, which allows allergens, pollutants, or microbes to enter the tissue and activate the immune response. The aim of this study was to establish a method to directly assess in vivo the epidermal barrier function by electrical impedance (EI) spectroscopy. Mice epidermal barrier was damaged by epicutaneous application of proteases and cholera toxin and by tape stripping. EI and transepidermal water loss (TEWL) were measured before and after the application. Additionally, histological analysis, immunofluorescence staining, and RT-PCR were performed on skin biopsies to evaluate the epithelial barrier. A few hours after papain application, a dose-dependent reduction of EI was detected, reflecting the decreased barrier function. At the same time, an increase of TEWL was observed, with a significant negative correlation with EI, demonstrating that EI changes were directly linked to barrier defects. Twenty-four and 48hours after the treatment, EI starts to increase to background levels, indicating tissue healing and restoration of skin barrier. Barrier disruption was confirmed by histological analysis showing an impaired stratum corneum and higher cellular infiltration after papain application. In addition, immunofluorescence staining and RT-PCR showed downregulation of molecules involved in the barrier function, such as filaggrin, occludin, and claudin-1, and mRNA levels of filaggrin, loricrin, and involucrin. Comparable results were observed after tape stripping and cholera toxin treatment. Electrical impedance spectroscopy is a rapid and reliable diagnostic tool to detect skin barrier defects.

Impaired skin barrier function caused by reactive oxygen species in mice with colonic tumours

Purpose: We have previously reported that skin barrier function is disrupted in mice with colonic tumours induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). We postulated that the impaired skin barrier function was associated with reactive oxygen species derived from gp91phox. In this study, we investigated the mechanisms underlying the impaired skin barrier function using gp91phox−/− mice.Materials and methods: We induced colonic tumorigenesis in C57BL/6j mice by AOM + DSS administration and evaluated the influence of reactive oxygen species on skin barrier function by using the hydroxyl radical scavenger N-acetyl-l-cysteine (NAC) or gp91phox−/− mice. Damage to the colon and skin following treatment with AOM + DSS was monitored using protein analysis methods and by detection of inflammatory mediators in the plasma.Results: NAC could not prevent the increase in transepidermal water loss (TEWL) and decrease in skin hydration level caused by AOM + DSS in gp91phox+/+ mice. However, gp91phox−/− mice showed no change in TEWL and skin hydration level. The dermal expression levels of nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3), and caspase-1 were reduced in gp91phox−/− mice. Moreover, the plasma concentrations of interleukin-18 and thymic stromal lymphopoietin (TSLP) were lower in gp91phox−/− mice than those in gp91phox+/+ mice. Inhibition of hydrogen peroxide production from superoxide anions in the gp91phox−/− status prevented the increased TEWL and decreased skin hydration level noted with degradation of NLRP3 and caspase-1.Conclusions: Superoxide anions may play an important role in the onset of the impaired skin barrier function in mice with colonic tumours.

The influence of incontinence pads moisture at the loaded skin interface

AimProlonged mechanical loading on soft tissues adjacent to bony prominences can lead to pressure ulcers. The presence of moisture at the skin interface will lower the tolerance to load. Absorbent pads manage moisture in individuals with incontinence, although their role in maintaining skin health is unknown. The present study investigated the effects of moist incontinence pads on skin physiology after periods of mechanical loading. Material and methodsTwelve healthy participants were recruited to evaluate a single incontinence pad design under three moisture conditions: 0% (dry), 50% and 100% fluid capacity. For each pad condition, pressure (9 kPa) or pressure in combination with shear (3 N) was applied to the sacrum, followed by a period of off-loading. Measures included trans-epidermal water loss (TEWL) and inflammatory biomarkers sampled at the skin interface. ResultsResults revealed no change in TEWL in the loaded dry pad condition. By contrast, when the pads contained moisture, significant increases in TEWL were observed. These increases were reversed during off-loading. Inflammatory biomarkers, specifically IL-1α/total protein ratio, were up-regulated during dry pad loading, which recovered during off-loading. Loaded moist pads caused a significant increase in biomarkers, which remained elevated throughout the test period. ConclusionThe study revealed a marked compromise to stratum corneum integrity when the skin was exposed to moist incontinence pads in combination with mechanical loads. These physiological changes were largely reversed during off-loading. Incontinence pads provided some protection in the dry state, although more research is required to determine optimal clinical guidance for their use.

Th2 and Th17 Induce Dry Skin in a Mouse Model of Arthritis.

Skin dryness is a characteristic of rheumatoid arthritis (RA) model mice. However, the mechanism underlying the induction of dry skin by RA is unclear. We hypothesized that T helper (Th)2 and Th17 cells mediate this process. A mouse model of DBA/1JJmsSlc collagen-induced arthritis was treated with Th2 or Th17 cell inhibitor, and transepidermal water loss (TEWL) and the expression of markers associated with allergic reaction and inflammation were evaluated. TEWL and plasma levels of thymic stromal lymphopoietin, interleukin (IL)-6 and -17, and tumor necrosis factor (TNF)-α were increased in the arthritis mouse model compared to that in control mice. Administration of Th2 cell inhibitor abolished the increase in TEWL, IL-6, and TNF-α levels, whereas Th17 cell inhibitor reversed TEWL and decreased IL-17 level. Th2 and Th17 cells contribute to the induction of dry skin, but via distinct mechanisms.

Abstract P4-16-07: The CHANCE study: Mechanical skin changes among women with non-metastatic breast cancer receiving chemotherapy and endocrine therapy

Abstract Background: The persistent effects on skin hydration and elasticity resulting from cytotoxic and endocrine agents used in early stages of breast cancer are poorly understood. The objective of this preliminary analysis of the CHANCE study is to describe the pattern of persistent biomechanical skin changes in non-metastatic breast cancer patients treated with cytotoxic chemotherapies and/or endocrine therapies. Methods: This is an ongoing single-center, prospective, longitudinal cohort study of non-metastatic breast cancer patients treated with cytotoxic chemotherapies and/or endocrine therapies. Objective skin hydration and elasticity measurements of the forearm were measured using Tewameter® (TM 300; Courage & Khazaka) and Cutometer® (MPA 580; Courage & Khazaka) devices under a controlled ambient environment at baseline and 6 months after chemotherapy completion, or one year after initiation of endocrine therapy. Results: A total of 107 patients were assessed at baseline and follow-up for transepidermal water loss (TEWL) (median age 53, range 26-82) and 106 patients for skin elasticity (median age 53.5, range 26-82). Fifty-three healthy controls were evaluated at baseline with median age 47 (range, 22-73). The mean TEWL at baseline and follow-up among patients were 6.922 g/h/m2 and 8.521 g/h/m2, respectively (p<.0001). Skin firmness (0.420 versus 0.421 mm, p=0.949) and elasticity (77.2% versus 77.4%, p=0.836) did not significantly change during follow-up. When comparing chemotherapy recipients with endocrine therapy recipients, chemotherapy patients had a mildly lower TEWL at follow-up (8.369 versus 8.928 g/h/m2, p=.247) but a greater net increase in TEWL (1.687 versus 1.359 g/h/m2, p=.5) compared to endocrine patients over the study period. Conclusions: An increase in TEWL was observed in patients receiving cytotoxic and endocrine therapies, suggesting a deterioration of the protective skin barrier possibly attributed to these therapies. No significant changes in skin firmness or elasticity were found in this preliminary analysis. Further studies are needed to elucidate the pathophysiologic mechanisms involved in persistent skin changes after systemic breast cancer therapies. Objective skin hydration and elasticity in patients receiving breast cancer therapy Control (n=53)Baseline (n=107)Follow-Up (n=107)p-value*TEWL (g/h/m2)9.4626.9228.521<.0001Cutometer Baseline (n=106)Follow-Up (n=106) Immediate recovery, R0 (mm)0.4150.4200.4210.949Gross elasticity, R2 (%)79.3%77.2%77.4%0.836*p-value calculated from baseline and follow-up only Citation Format: Lacouture ME, Phillips GS, Freites-Martinez A, Patil S, Samuels A, Shapiro J, Kukoyi O, Goldfarb S. The CHANCE study: Mechanical skin changes among women with non-metastatic breast cancer receiving chemotherapy and endocrine therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-07.

Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer

In spite of the high incidence of breast cancer worldwide, there are few strategies for its chemoprevention, and they have limited adherence mainly due to their serious adverse effects. As a new approach for local breast cancer chemoprevention, we developed and optimized microemulsions for topical delivery of celecoxib to the breast skin, and evaluated their combination with microneedles to improve drug penetration for localization in the mammary tissue. Microemulsions containing water at 15% (ME-15), 29% (ME-29) and 60% (ME-60) were obtained and characterized. They were isotropic, displayed Newtonian behavior and particle size smaller than 100 nm. ME-15 and ME-29 increased transepidermal water loss (TEWL) compared to ME-60, and displayed stronger vascular toxicity, evidenced by hemorrhage and lysis in HET-CAM assays. ME-60 was more efficacious at increasing celecoxib cutaneous and percutaneous delivery (1.3–4-fold). Increasing the number of microneedle roller applications from 1 to 8 increased the number of skin punctures and TEWL; its association with ME-60 promoted no further increase in TEWL, but improved (1.6–4-fold) celecoxib cutaneous and percutaneous delivery. Microemulsion incorporation reduced celecoxib IC50 in MCF-7 cells (3.3-fold), suggesting that presence of formulation components in the mammary tissue might improve drug cytotoxicity.

Skin Barrier Damage and Itch: Review of Mechanisms, Topical Management and Future Directions.

Barrier damage, dry skin and itch are intricately linked and form the basis of many common skin diseases. Damage from environmental insults, or genetic or inflammatory causes, can impair the skin barrier, resulting in an increase in transepidermal water loss and activation of itch-associated nerve fibres. The itch-scratch cycle can perpetuate skin barrier damage and itch. Topical therapeutic strategies are utilised to overcome dry skin and itch, primarily in the form of emollients. Recent advances in our understanding of the mechanisms underlying itch have enabled the development of new topical therapies, which may be incorporated into existing treatment regimes. Ultimately, treatment of dry skin and itch must be highly tailored to the individual according to their needs.

Selective Inhibition of β-Catenin/Co-Activator Cyclic AMP Response Element-Binding Protein-Dependent Signaling Prevents the Emergence of Hapten-Induced Atopic Dermatitis-Like Dermatitis.

BackgroundThe canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated.ObjectiveTo investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD.MethodsWe examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment.ResultsOx-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance.ConclusionThese results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.

Multi-Center Randomized Clinical Study of The Effects of Natural Oils on Xerosis and Skin Barrier Properties

Objective: To compare the effect of natural oils and white petrolatum on skin barrier function in patients with xerosis.Design, Setting, and Participants: Randomized, open label, comparison pilot study (NCT03093597).Interventions: Participants were randomized to apply 1 of 4 moisturizers to assigned treatment areas twice daily for 2 weeks. Clinical dry skin score, stratum corneum hydration, and transepidermal water loss (TEWL) were assessed at baseline, 1 week, and 2 weeks.Results: Thirty-two participants completed the study. Neither TEWL nor hydration were statistically different among the moisturizers at each visit. All four moisturizers led to significant initial increase in TEWL at week 1 (p < 0.05) with an associated increase in hydration for coconut oil, jojoba oil, and white petrolatum. All four moisturizers led to significant increase in hydration by week 2 (p < 0.01). The preferred moisturizers were almond oil and coconut oil, which were most “liked” by 38% and 31% of the participants, respectively. The least preferred moisturizer was white petrolatum. Conclusions: Almond oil, jojoba oil, and coconut oil significantly increased hydration after 2 weeks, and are as effective as white petrolatum as daily moisturizers for xerosis. The participants preferred natural oils to white petrolatum, implying that these moisturizer options may improve patient compliance.

Seasonal changes in epidermal ceramides are linked to impaired barrier function in acne patients.

Acne skin demonstrates increased transepidermal water loss (TEWL) compared with healthy skin, which may be due, in part, to altered ceramide (CER) levels. We analysed ceramides in the stratum corneum of healthy and acne skin, and studied seasonal variation over the course of a year. Using ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry (UPLC/ESI-MS/MS), we identified 283 ceramides. Acne-affected skin demonstrated overall lower levels of ceramides, with notable reductions in CER[NH] and CER[AH] ceramides, as well as the acylceramides CER[EOS] and CER[EOH]; these differences were more apparent in the winter months. Lower ceramide levels reflected an increase in TEWL in acne, compared with healthy skin, which partly resolves in the summer. Individual ceramide species with 18-carbon 6-hydroxysphingosine (H) bases (including CER[N(24)H(18)], CER[N(26)H(18)], CER[A(24)H(18)], CER[A(26)H(18)]) were significantly reduced in acne skin, suggesting that CER[NH] and CER[AH] species may be particularly important in a healthy skin barrier.

Numerical Simulation of Skin Formation: The Relationship between Transepidermal Water Loss and Corneum Thickness

Skin moisturizing has drawn attention in terms of beauty and anti-aging industries. However, it is difficult to observe the inside of the epidermis and the relationship between the epidermis and water content is not yet clear. Computational simulations can be useful in understanding such mechanisms of skin formation. A particle model was used to simulate three-dimensional skin turnover, and the results reproduced the epidermal skin turnover phenomenon. In this study, a diffusion model is introduced into this simulation model and a moisture diffusion analysis of the epidermis was performed. In particular, transepidermal water loss (TEWL) was modeled by considering diffusion and surface evaporation in the stratum corneum and other layers. The relationship between the moisture content and the keratin detachment was considered, and the exfoliation condition of keratin based on the moisture content was calculated in the model. As a result, it was possible to calculate the intraepidermal water content distribution in the skin using the particle model. It was also possible to reproduce phenomena such as keratin thickening due to increase of TEWL. This phenomenon is consistent with cases of dry skin. In the future, it will be necessary to introduce a change in TEWL according to the thickness of the stratum corneum and the diffusion coefficient.

Inhibitory effect of vitamin C on intrinsic aging in human dermal fibroblasts and hairless mice.

Vitamin C significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity, with both the suppression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulation of cell-cycle activators (E2F1 and E2F2). Vitamin C also effectively attenuated the hyperactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase-B (AKT) signaling pathway. The expression of the longevity marker, the mammalian target of rapamycin (mTOR), was down-regulated by vitamin C while the expressions of forkhead box O3a (FoxO3a) and sirtuin1 (SIRT1) were up-regulated by vitamin C. In the middle-aged (MA) mice, oral administration of vitamin C significantly inhibited wrinkle formation, skin atrophy, and loss of elasticity through increasing collagen and elastic fiber. The increase in transepidermal water loss and the decrease in skin hydration were recovered by vitamin C treatment in the MA mice. Overall, vitamin C effectively prevents cellular senescence in vitro and in vivo suggesting it has protective potential against natural aging of the skin.