Transepidermal Water Loss Rates Research Articles

Anti-inflammatory Capacity of a Medicinal herb extract, Anemarrhena asphodeloides, on In vivo and In vitro models-induced atopic dermatitis

Anemarrhena asphodeloides (AA) Bunge, a rhizomatous plant from the Liliaceae family, is traditionally utilized to manage inflammatory conditions. Nevertheless, its impact on atopic dermatitis (AD) and the associated molecular pathways have not yet been fully explored. This study explored the therapeutic effects of AA on AD both in vivo, using 2,4-dinitrofluorobenzene-induced NC/Nga mice, and in vitro, with tumor necrosis factor-α/interferon-γ-stimulated HaCaT keratinocytes. Topical application of AA ointment on the dorsal skin notably alleviated AD symptoms and skin lesions, enhanced the dermatitis score, and improved parameters such as the rate of trans-epidermal water loss, epidermal thickness, mast cell infiltration, systemic IgE levels, and cytokine expression. Furthermore, AA treatment significantly reduced serum levels of thymic stromal lymphopoietin (TSLP) and locally suppressed mRNA expression of thymus and activation-regulated chemokine (TARC) along with other relevant cytokines in affected skin. Both in vivo and in vitro applications of AA curtailed TSLP levels by inhibiting the expression of signal transducer and activator of transcription 6, a key regulator of pruritus and an initiator of mitogen-activated protein kinase signaling pathways. Additionally, AA affected the expression of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, a pathway of interest in the study of cutaneous inflammatory diseases. Collectively, these findings propose that AA holds potential as an effective therapeutic agent for treating AD-induced skin inflammation.

Characterization of Epidermal Function in Individuals with Primary Cutaneous Amyloidosis.

To compare epidermal biophysical properties, indicators of epidermal function, in individuals with and without primary cutaneous amyloidosis (PCA). This study incorporated 189 patients with PCA and 166 healthy individuals. The GPSkin Barrier was employed to measure transepidermal water loss (TEWL) rates and hydration levels of the stratum corneum. The Sebumeter and the Skin pH Meter were utilized to determine the skin surface's sebum content and pH, respectively. The severity of pruritus in participants was evaluated using the visual analog scale (VAS). Compared to the control group without PCA, individuals with PCA displayed a notable increase in skin surface pH and TEWL and a decrease in the hydration levels of the stratum corneum (p<0.0001 for all parameters). Additionally, the sebum content was markedly lower in those with PCA than in the controls (p<0.0001). Of particular note, both TEWL and skin surface pH at the lesion sites on the back and the shin were more elevated in lichenoid amyloidosis (LA) and in macular amyloidosis (MA), whereas hydration levels of the stratum corneum and sebum levels were diminished in LA compared to MA (p<0.05). In conclusion, both hydration levels of the stratum corneum and sebum content exhibited an inverse relationship with pruritus severity, whereas TEWL and skin surface pH demonstrated a positive correlation with pruritus intensity. The function of the epidermis is compromised in individuals diagnosed with PCA. However, the mechanisms underlying these changes await further investigation.

Rosacea and seborrheic dermatitis differentially respond to lactic acid sting and capsaicin tests in Chinese women.

Although rosacea and seborrheic dermatitis share some symptoms of sensitive skin, whether they respond differently to lactic acid sting and capsaicin tests, common tests for diagnosis of sensitive skin, is unknown. To reveal the cutaneous responses to lactic acid sting (LAST) and capsaicin test (CAT) in females with either rosacea vs. seborrheic dermatitis. A total of 60 patients with rosacea, 20 patients with seborrheic dermatitis and 40 normal controls were enrolled in the study. Their skin sensitivity to stimuli were evaluated following topical application of either 10% lactic acid solution or 0.001% capsaicin solution. Transepidermal water loss (TEWL) rates and erythema indexes were also measured on the face. In comparison to normal controls, the positive rate to either LAST or CAT was significantly higher in subjects with rosacea (p < 0.001), but not in that with seborrheic dermatitis. Similarly, individuals with rosacea displayed a higher positive rate to both LAST and CAT than those with seborrheic dermatitis and normal controls (p < 0.001). In parallel, the LAST scores and CAT scores in individuals with rosacea were significantly higher than in that with either seborrheic dermatitis or normal controls (p < 0.001). The baseline TEWL rates and erythema indexes were higher in individual with rosacea than in normal controls (p < 0.001). But the baseline TEWL rates and erythema indexes did not differ significantly between subjects with rosacea and that with seborrheic dermatitis. Moreover, LAST scores and CAT scores correlated positively with TEWL (p < 0.0001). TEWL rates were higher in CAT positive than in CAT negative subjects (p < 0.0001). Finally, erythema index correlated positively with CAT scores (p < 0.0001), but not with LAST scores (p = 0.0842). Skin responses to LAST and CAT differ between individuals with rosacea and those with seborrheic dermatitis, possibly due to the differences in epidermal permeability barrier and the neurovascular hyperreactivity. The higher LAST and CAT scores, as well as positive rates of both LAST and CAT can be attributable to inferior permeability barrier and the neurovascular hyperreactivity in subjects with rosacea.

Directional assessment of the skin barrier function in vivo.

The fundamental function of the epidermis is to provide an inside-out barrier to water loss and an outside-in barrier to penetration of external irritants. Transepidermal water loss (TEWL) has been extensively used as a method of estimating the skin barrier quality, typically without any consideration of directionality. The validity of TEWL as an estimate of skin permeability to external substances has been controversial in vitro and in vivo. The aim of this work was to assess the relationship between TEWL and the penetration of a topically applied external marker (caffeine) in healthy skin in vivo before and following a challenge to the barrier. The skin barrier was challenged by application of aqueous solutions of mild cleanser products under occlusion for 3h on the forearms of nine human participants. Skin barrier quality was evaluated before and after the challenge by measuring the TEWL rate and the permeated amount of topically applied caffeine using in vivo confocal Raman microspectroscopy. No skin irritation was observed following the skin barrier challenge. TEWL rates and the caffeine penetrated amount in the stratum corneum after the challenge were not correlated. A weak correlation was observed when the changes were corrected to water-only treatment. TEWL values can be influenced by environmental conditions as well as the skin temperature and water content. Measuring TEWL rates is not always representative of the outside-in barrier. TEWL may be useful in differentiating large changes in skin barrier function (e.g., between healthy and compromised skin) but is less sensitive to small variations following topical application of mild cleansers.

Trend of changes in epidermal biophysical properties in the Chinese aged 1 month to 17-year old.

Although it is known that epidermal biophysical properties vary with age and gender, the changes in epidermal biophysical properties over the time from baby to adolescence have not been elucidated yet. In the present study, we assessed the trend of changes in transepidermal water loss rates (TEWL), stratum corneum hydration, and skin surface pH in Chinese children. A total of 780 boys and 610 girls, aged 1 month to 17-year old, were enrolled in this study. TEWL and stratum corneum hydration on theforearmandtheshinwere measured with GPSkin Barrier, whereas skin surface pH was measured with portable skin pH meter. Overall, TEWL and stratum corneum hydration levels decreased, whereas skin surface pH increased in children from 1-month old to 17-year old. Significant decline in TEWL was observed on both the forearm and the shin of girls, and the shin of boys aged 13-17-year old. Similarly, marked decline in stratum corneum hydration levels started at ages of 6-12-year old. In contrast, decline in skin surface pH was observed in both girls and boys aged one to 12-month old except on the forearm of boys. Afterward, skin surface pH remained either stable or slight increase except on the shin of boys aged >12 months to 3-year old. These results demonstrate that both TEWL and stratum corneum hydration levels decrease, whereas skin surface pH increases in children aged 1 month to 17-year old. The changes in these biophysical properties vary with age, gender, and body site.

Study on the Skin Hydration and Trans Epidermal Water Loss of Aloe Viscose Seamless Knitted Fabric for Autumn and Winter

To explore the skin moisturizing performance of aloe viscose fiber seamless knitted fabric, this experiment takes the different yarn-blending ratios of aloe viscose fiber and viscose fiber, as well as three different tissue structures as factors, establishes a sample scheme according to full factor experimental tests on skin hydration and trans epidermal water loss (TEWL) after the sample fabric had been wrapped around the skin, and uses two-way and one-way ANOVA in SPSS and the Duncan multiple comparison method. The test data were analyzed to study the influence of different materials and the structure of the veil on the moisture retention of the fabric. The results show that the sample scheme with the largest change rate of skin hydration is when the raw material of the veil is aloe viscose/viscose 100/0 yarn, and the structure is 1 + 3 simulated rib. The sample scheme with the minimum change rate of TEWL is when aloe viscose/viscose 75/25 yarn is used as the raw material of the veil, and the structure is 1 + 1 simulated rib, which provides a theoretical basis for the research and development of moisturizing knitted fabric.

Jade material in vitro and in vivo: A study on the anti-inflammatory and repair efficacy of jade material on the skin.

The biological safety of natural jade materials and assembled jade-activated materials on cells and their anti-inflammatory and damage repair functions, as well as the repair function on sensitive skin, were studied utilizing in vitro cell biology and in vivo. Human skin fibroblasts were used as model cells to conduct cytotoxicity experiments in vitro, and the effects on the expression of inflammatory factors and growth factor-related genes in fibroblasts were explored. The gene expression values of inflammatory factors IL-1, IL-6, TNF-α and cytokines epidermal growth factors, fibroblast growth factors and COL1A1 in fibroblasts were measured by polymerase chain reaction test. Thirty women with sensitive skin were selected to apply a mask containing jade extract three times a week. After two weeks, non-invasive measures related to skin sensitivity were tested. We confirmed the presence of anti-inflammatory effects in both jade materials, with the effects of the assembled activated jade material being superior to that of the natural jade material. Jade extracts significantly increased the gene expressions of EGF, FGF and COL1A1 in HDF. The results of the in vivo study showed that the mask containing jade extract could significantly increase the skin hydration and decrease the rate of transepidermal water loss and skin lactic acid sting test scores after two weeks of use. Subjective evaluations confirmed improvements in skin dryness, smoothness and fineness. No new sensitization occurred in subjects, and the product was non-irritating. No adverse skin reactions were observed during the test. The jade materials were able to downregulate the expression of inflammatory factor genes, up-regulate the expression of growth factor genes, and improve the anti-inflammation and repair ability of skin. Furthermore, the test results of participants with sensitive skin after using the mask containing jade extract showed that the mask has repairing ability.

Multispectral raster-scanning optoacoustic mesoscopy differentiate lesional from non-lesional atopic dermatitis skin using structural and functional imaging markers

Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient’s quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier defects and immune response, which can develop to AD at a later stage. To investigate further the balance between the epidermal barrier impairment and intrinsic immune dysregulation in AD, we exploited multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) to image lesional and non-lesional skin areas on AD patients of different severities non-invasively to elucidate their structural features and functional information. Herein, we demonstrate the objective assessment of AD severity using relative changes in oxygen saturation (δsO2) levels in microvasculature along with other structural parameters such as relative changes in epidermis thickness (δET) and total blood volume (δTBV) between the lesional and non-lesional areas of the skin. We could observe an increasing trend for δsO2 and δTBV, which correlated well with the subjective clinical Scoring Atopic Dermatitis (SCORAD) for evaluating the severity. Notably, δET showed a decreasing trend with AD severity, indicating that the difference in epidermal thickness between lesional and non-lesional area of the skin decreases with AD severity. Our results also correlated well with conventional metrics such as trans-epidermal water loss (TEWL) and erythrosine sedimentation rate (ESR). We quantified the δsO2 and δET changes to objectively evaluate the treatment response before and four months after treatment using topical steroids and cyclosporine in one severe AD patient. We observed reduced δsO2 and δET post treatment. We envision that in future, functional and structural imaging metrics derived from ms-RSOM can be translated as objective markers to assess and stratify the severity of AD and understand the function of skin barrier dysfunctions and immune dysregulation. It could also be employed to monitor the treatment response of AD in regular clinical settings.

Study on screening and evaluation methods of cosmetics for people with facial sensitive skin.

Objective:The purpose of this study is to screen and evaluate cosmetic products for sensitive skin on the face.Methods:Thirty-five subjects with positive lactic acid sting test (LAST) were recruited from the staff of our hospital from November 2019 to February 2020. First, the human skin enclosed patch test of cosmetic gel (abbreviated as gel) was performed, and then the tested products were continuously applied for 4 weeks to complete the long-term efficacy test. Subjects’ sensation of application, pruritus, tingling and burning were assessed on a 0 to 9 scale prior to, 14, and 28 days after topical application. Moreover, the transepidermal water loss rate (TEWL), stratum corneum (SC) hydration, melanin index (MI), erythema index (EI) and dendritic cells and inflammatory cell infiltration were noninvasively detected by the tester. LAST were performed before applying, 14 and 28 days after application, and then the test results were compared.Results:In this study, a total of 34 people participated in the test. The results of human skin enclosed patch test indicated that only 1 case of grade 1 reaction occurred among the tested subjects. The subjects felt good after applying the products, and the gel showed high degree of skin comfortable, no irritation and good tolerability. Subjective safety evaluation illustrated that the scores of pruritus, tingling and burning of the subjects decreased in D14 and D28 patient revisit, showing statistically significant differences (P < .05). When the gel was applied for 4 weeks, TEWL (8.42 ± 1.12) and EI (201.35 ± 13.51) were lower than the results before application (P < .05), and the SC hydration (65.36 ± 2.56) was higher than that before application (P < .05). There was no correlation between the SC hydration and TEWL (R = 0.092, P = .416). The results of skin CT indicated that the number of facial dendritic cells decreased in 17 subjects (accounting for 50%) in D28 patient revisit, and the degree of inflammatory cell infiltration decreased in 27 subjects (accounting for 80%). Compared with the baseline value, the LAST score and total sensory score decreased after application the product for 4 weeks, and the difference was statistically significant (the mean value of P < .05).Conclusion:The subjective feeling of application and efficacy of cosmetics in people with sensitive skin could be successfully evaluated by the comprehensive application of human skin enclosed patch test, long-term trial test, subjective safety evaluation and objective efficacy evaluation. And it provides the basis to judge whether the cosmetic is consistent with the efficacy claim of sensitive skin.

412 An emollient attenuates the progression of cognitive impairment in the elderly

Cognitive impairment (CI) is common in the elderly. Prior studies suggest a link between chronic inflammation and CI. Additionally, an age-associated increase in cutaneous cytokines has been connected to elevated circulating cytokines. We therefore assessed here whether topical emollient can mitigate the progression of CI. Methods: This randomized, open-label pilot trial was carried out in Dalian and Shenyang, in northern China. Eligible participants were ≥65 years old and were randomly assigned to the treated and untreated groups at 1:1 ratio. The treated group were treated topically with Atopalm cream® twice-daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of CI in November and the following May of each year, while epidermal biophysical properties were measured on the forearms and the shins. Results: A total of 200 eligible participants, including 63 males and 137 females, aged 75.83 ± 0.62 years were enrolled. Over the 3-year trial, GDS increased significantly in the controls, while in the treated group, GDS remained stable. While stratum corneum hydration (SCH) on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls. Skin surface pH declined slightly in the controls. On the forearms of the treated group, SCH increased significantly, while surface pH markedly decreased. TEWL was comparable before and after the trial. These results demonstrate that improvements in epidermal function can mitigate the progression of CI. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.

Facial skin ageing: Key concepts and overview of processes.

IntroductionThe face is a cosmetically sensitive region where the process of ageing is most clearly manifested. With increased focus on anti‐ageing and longevity, more anti‐senescent treatments are being proposed despite limited evidence. This study outlines the pathways and mechanisms underpinning the biological process of ageing in the face.MethodsComprehensive searches of MEDLINE, EMBASE, Cochrane Library and CINAHL from inception to 2020. Inclusion criteria included all empirical human research studies specific to facial ageing features, written in the English language.ResultsA total of 65 papers met inclusion criteria for analysis. Pathways were subdivided into intrinsic and extrinsic senescence mechanisms. Intrinsic pathways included genetics, generation of reactive oxygen species and hormonal changes. Extrinsic pathways included photoageing and damage to skin layers. The combined intrinsic and extrinsic pathway alterations result in wrinkles, higher laxity, slackness and thinning of the skin. Skin functions such as barrier immune function, wound healing, thermoregulation and sensory function are also impaired.ConclusionThe ageing process is unique to the individual and depends on the interplay between an individual's genetics and external environmental factors. Through understanding the molecular and cellular mechanisms, an appreciation of the consequent structural and functional changes can be achieved. Based on this knowledge, further research can focus on how to slow or impede the ageing process and identify specific targets to develop and evolve new treatment strategies.

A topical emollient mitigates the progression of cognitive impairment in the elderly: a randomized, open-label pilot trial.

Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging-associated epidermal dysfunction has been connected to elevations in circulating cytokines. We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. This randomized, open-label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient-treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice-daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. Over the three-year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.

Epidermal barrier function in human immunodeficiency virus-infected South African infants compared with uninfected.

Infant human immunodeficiency virus (HIV) infection remains a problem in different parts of the world. Early signs of disease manifestation often involve infant skin. This study compared the skin barrier properties of HIV infected with uninfected infants. A cross-sectional descriptive study was undertaken with HIV positive and HIV negative unexposed African infants (6 weeks-12 months). Both had normal birth weight for age, no pre-existing dermatoses or co-infections, and received all their vaccinations timeously. The HIV positive infants were on antiretroviral (ARV) therapy. The skin barrier quality was assessed by measuring the transepidermal water loss (TEWL) and skin surface hydration (SSH) on the dorsal arm (1) and the inner forearm (2). Eighty-six HIV negative and 43 HIV positive African children were recruited. There were significant differences between the two groups based on the presence of HIV infection. In both sites, measured TEWL rates were significantly higher for the HIV positive children. There was a nonsignificant difference between the SSH values for site 1 and a marginally significant difference for site 2, with the average values higher in the HIV positive group. In both groups, TEWL rates and SSH values were significantly lower on site 1 compared to site 2. Differences in skin barrier properties of HIV infected and uninfected children may exist. The altered skin barrier in infected children may be one of the factors that predisposes them to various inflammatory and infectious dermatoses. Improving the skin barrier may assist in preventing these conditions.

Topical therapy of dermatoses in children with complex localizations

The skin of children has its own anatomical and physiological characteristics, the epidermis is much thinner than in adults, the layers of the dermis and basement membrane are poorly developed and differentiated, the rate of transepidermal water loss is increased and the level of natural moisturizing factor (NMF) is reduced. Such a structure of the skin predisposes to a violation of its barrier function, contributes to the occurrence of skin diseases, provides an increased resorptive capacity of the skin and requires special attention when prescribing external therapy. The use of high-quality emollients is an important part of the basic treatment of chronic dermatoses and has its own characteristics in childhood. The use of emollients prevents the development of exacerbations and reduces the need for anti-inflammatory topical drugs. With the localization of the inflammatory process on the face, neck, genitals and large folds, it is necessary to give preference to short courses of topical glucocorticosteroids (THCS) with sufficient anti-inflammatory activity, rapid onset of action, minimal side effects. Given the high risk of side effects in children in these areas of the skin, strong fluorinated THCS, high-potency THCS, and the use of THCS under occlusive dressings are not recommended. The Russian experience of using 0.1% methylprednisolone aceponate in children of various age groups in the treatment of allergic dermatoses, including those with localization in sensitive areas, has shown good efficacy, tolerance and the absence of side effects. he article presents own clinical observations of the effectiveness of the use of combination therapy: an emollient agent - a special cream with physiological lipids omega 3-6-9 and cream methylprednisolone aceponate (with ceramides in the base) in the treatment of skin diseases in children with an emphasis on complex localizations, such as face, folds, genital area.

Either transepidermal water loss rates or stratum corneum hydration levels can predict quality of life in children with atopic dermatitis.

ABSTRACTImportancePatients with atopic dermatitis (AD) display compromised epidermal barrier and suffer from poor quality of life. We hypothesized that quality of life could reflect in the changes in the epidermal barrier function.ObjectiveTo determine whether the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with AD.MethodsA total of 120 children, aged 0–12 years, with moderate AD were enrolled. Children were topically treated with topical corticosteroids (TCS) and an emollient for 2 weeks. The Eczema Area and Severity Index (EASI), visual analogue scale (VAS) for pruritus severity, the Infant’s Dermatitis Quality of Life Index (IDQOL) and the Children’s Dermatology Life Quality Index (CDLQI) were evaluated. Transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration, and skin surface pH were measured. Correlations of epidermal barrier function with pruritus, life quality, and EASI were determined.ResultsFollowing 2‐week treatments, significant improvements were observed in EASI, TEWL, SC hydration, the VAS of pruritus, as well as DQOL (P < 0.001 for all). TEWL positively, while SC hydration negatively correlated with VAS pruritus, DQOL, and EASI (P < 0.001).InterpretationBoth TEWL and SC hydration levels can serve as indicators of the severity of pruritus and quality of life in children with AD.

A new combined method for the treatment of involutional changes in the periorbital region

Background. The solution to the problem of correction of involutional changes in the periorbital region requires a multidisciplinary approach, as this location can comprise a broad range of problems that need to be addressed. For so many years, laser therapy methods have been the standard for correcting age-related changes. However, many issues concerning combined methods remain open, and the search and development of the most effective protocols for their use is therefore an urgent task of modern medicine.&#x0D; Objective. The goal of the study was to develop a combined method to correct involutional skin changes in the periorbital region in young and middle-aged patients using a fractional Nd:YAG and CO2 laser in conjunction with lower transconjunctival blepharoplasty, based on the study of clinical efficacy results and taking into account the indicators of the qualitative characteristics of the skin, as well as microcirculation.&#x0D; Material and methods. The study enrolled 108 patients with involutional changes in the skin of the lower eyelid. These patients were classified into groups based on the method of treatment. In the study, relevant methods were used, namely, the study of the qualitative characteristics of the skin (cutometry, TEVA-metry, and corneometry) and microcirculatory processes using laser flowmetry.&#x0D; Results. The effectiveness of the developed combined method is based on a substantial positive impact on active and passive hemodynamic mechanisms at all levels of the microvasculature, as demonstrated by an increase of 45.92% in the integral indicator of microcirculation compared to 26.35% and 5.77% in the comparison groups, while the coefficient of variation in the microcirculation indicator increased by 33.02% compared to 24.19% and 6.46% following the use of the method components. The use of the combined treatment method restores the qualitative characteristics of the skin, namely, the moisture index increased by 27% (p 0.05) compared to 14.1% and 7.8% in groups 1 and 2, respectively; the rate of transepidermal water loss decreased by 47% (p 0.05) compared to 35% and 12.7% in groups 1 and 2, respectively; and the elasticity index Ua/Uf increased by 23.2% (p 0.05) compared to 18.4% and 16.4% in groups 1 and 2, respectively.&#x0D; Conclusion. Based on the study, it can be concluded that the combined treatment method developed is highly effective.

Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

Will Repeated Low-Energy 1064-nm Q-Switched Nd:YAG Laser Treatment Sessions Affect Facial Skin Sensitivity? Results of a 12-Month, Prospective, Randomized Split-Face Study.

To compare changes in skin sensitivity before and after treatment with a 1064-nm Q-switched Nd:YAG laser in healthy individuals, and to provide a reference for clinicians to use this laser reasonably. Nineteen healthy female volunteers underwent 10 random unilateral 1064-nm Q-switched Nd:YAG laser treatments. The skin transepidermal water loss rate (TEWL), skin glossiness, epidermal and dermal thickness and density, current perception threshold (CPT) value, facial blood perfusion were determined before and after treatment at different time points. Moreover, the changes in skin barrier function, blood vessels, and sensory nerve reaction in the treated and untreated sides of the face were recorded before and after treatment. Seventeen volunteers completed the 12-month follow-up study after 1064-nm Q-switched Nd:YAG laser treatment. At D3, M3, and M6, skin TEWL was decreased on the treated side of the face. Skin glossiness was significantly improved in the early post-treatment period (D1-D7) and M3, M6, and M12 compared with the untreated side of the face. There was no significant change in dermal and epidermal thickness or density at all time points before and after treatment. There were no significant differences in sensory nerve CPT values and local blood flow volume or velocity between the treated side of the face and the untreated side before and after treatment. Multiple low-energy 1064-nm Q-switched Nd:YAG laser treatments will not affect the barrier function of facial skin, skin nerve sensitivity, or local microcirculation of healthy skin over the long term. Therefore, 1064-nm Q-switched Nd:YAG laser treatment is safe, and does not alter skin sensitivity. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function

BackgroundCutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45–100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient’s quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function.MethodsTo test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model.ResultsEGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype.ConclusionsThis study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

Mutations in 3β-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3β-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3β-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.