Corneocyte Desquamation Research Articles

Protein degradation in the stratum corneum.

The stratum corneum (SC), the outermost epidermal layer, plays a pivotal role in skin barrier function. This review delves into the intricate process of protein degradation within the stratum corneum, elucidating the roles of specific enzymes, regulatory mechanisms and the consequent impact on various skin conditions. Protein degradation is a finely tuned process, orchestrated by a suite of proteolytic enzymes like kallikreins. These enzymes are responsible for the breakdown of corneodesmosomes and the orderly desquamation of corneocytes, a process essential for skin homeostasis. Another critical enzymatic process is the breakdown of proteins like filaggrin and the generation of amino acids and their derivatives, required in the physiological water-handling properties of the SC. Regulation of these proteolytic activities is complex, involving a balance between endogenous inhibitors and other factors like pH, hydration and environmental stressors. Dysregulation of protease activity is linked to a spectrum of skin conditions, ranging from xerosis to inflammatory diseases like atopic dermatitis and psoriasis. Aberrant protein degradation can lead to compromised skin barrier function, increased tissue water loss and heightened susceptibility to infections and allergens. Understanding the factors affecting protein degradation can inform the development of targeted skincare products. Advances in biochemistry and dermatology have paved the way for the search for active ingredients designed to modulate protease activity. Such innovations may offer promising therapeutic avenues for enhancing skin barrier function and treating skin disorders. This review underscores the significance of enzymatic protein degradation in the SC and its regulatory mechanisms. It provides insights into the pathophysiology of skin diseases and outlines the potential for novel skincare interventions. By bridging the gap between fundamental research and practical applications, this article aims to inspire further investigation for better understanding of skin physiology and innovation in the realm of skincare product development.

KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors

BackgroundKallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells.MethodsTo comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.ResultsKLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p = 0.0005), blood vessel infiltration (p = 0.0037), and lymph vessel infiltration (p < 0.0001) in colorectal adenocarcinoma, nodal metastasis in hepatocellular carcinoma (p = 0.0382), advanced pathological tumor stage in papillary thyroid cancer (p = 0.0132), and low grade of malignancy in a cohort of 719 squamous cell carcinomas from 11 different sites of origin (p < 0.0001).ConclusionsThese data provide a comprehensive overview on KLK7 expression in normal and neoplastic human tissues. The prognostic relevance of KLK7 expression and the possible role of KLK7 as a drug target need to be further investigated.

Growth modulatory effects of fenretinide encompass keratinocyte terminal differentiation: A favorable outcome for oral squamous cell carcinoma chemoprevention.

Oral squamous cell carcinoma (OSCC) is world-wide health problem associated with high morbidity and mortality. From both the patient and socio-economic perspectives, prevention of progression of premalignant oral intraepithelial neoplasia (OIN) to OSCC is clearly the preferable outcome. Optimal OSCC chemopreventives possess a variety of attributes including high-tolerability, bioavailability, efficacy and preservation of an intact surface epithelium. Terminal differentiation, which directs oral keratinocytes leave the proliferative pool to form protective cornified envelopes, preserves the protective epithelial barrier while concurrently eliminating growth-aberrant keratinocytes. This study employed human premalignant oral keratinocytes and an OSCC cell line to evaluate the differentiation-inducing capacity of the synthetic retinoid, fenretinide (4HPR). Full thickness oral mucosal explants were evaluated for proof of concept differentiation studies. Results of this study characterize the ability of 4HPR to fulfill all requisite components for keratinocyte differentiation i.e. nuclear import via binding to CRABP-II (molecular modeling), binding to and subsequent activation of retinoic acid nuclear receptors (receptor activation assays), increased expression and translation of genes associated with keratinocyte differentiation (RT-PCR, immunoblotting) upregulation of a transglutaminase enzyme essential for cornified envelope formation (TGM3, functional assay) and augmentation of terminal differentiation in human oral epithelial explants (image-analyses quantified corneocyte desquamation). These data build upon the chemoprevention repertoire of 4HPR that includes function as a small molecule kinase inhibitor and inhibition of essential mechanisms necessary for basement membrane invasion. An upcoming clinical trial, which will assess whether a 4HPR-releasing mucoadhesive patch induces histologic, clinical and molecular regression in OIN lesions, will provide essential clinical insights.

Correlation between acne and insulin resistance; experience from central India.

Acne is a common dermatological condition primarily seen in teenage and adolescent patients and is a major concern for cosmological issues. Along with environmental factors, the proliferation of basal keratinocytes in the sebaceous-pilosebaceous unit, abnormal desquamation of follicular corneocytes, and metabolic abnormalities play a significant role in the pathogenesis of acne development. To study the causal relation between acne vulgaris and insulin resistance by calculating Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and identify the relation between insulin resistance and the severity of acne. This was a retrospective study, where the data of patients with persistent Acne Vulgaris who were referred to the Endocrine department for evaluation of the hormonal and metabolic causes for acne vulgaris were analysed. The patient's clinical records were evaluated in whom there was no significant hormonal or metabolic abnormality identified known to cause persistent acne were included after proper consent and HOMA-IR was calculated. Of several patients with persistent acne, 150 patients were included in our study with the male-to-female ratio was 23:27. The mean age of patients was 33.2 years. The mean HOMA-IR in our acne patients was 1.62 ranging from 0.9-3.7. Sixty four (42.67%) patients had HOMA-IR more than 2.0, thereby suggesting insulin resistance. Our study suggests the prevalence of insulin resistance in 42.67% of patients with acne, thereby providing the possibility of use of insulin modifiers as an adjunct acne treatment and stratifying the possible risk of metabolic syndrome in patients with acne. Also recommended is the control of dietary factors and lifestyle modification for the management of acne with insulin resistance.

Abstract 3302: KLK7 expression in human tumors: A tissue microarray study on 13,447 tumors

Abstract Background: Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells. Methods: To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p=0.0005), blood vessel infiltration (p=0.0037), and lymph vessel infiltration (p&amp;lt;0.0001) in colorectal adenocarcinoma, nodal metastasis in hepatocellular carcinoma (p=0.0382), advanced pathological tumor stage in papillary thyroid cancer (p=0.0132), and low grade of malignancy in a cohort of 719 squamous cell carcinomas from 11 different sites of origin (p&amp;lt;0.0001). Conclusions: These data provide a comprehensive overview on KLK7 expression in normal and neoplastic human tissues. The prognostic relevance of KLK7 expression and the possible role of KLK7 as a drug target need to be further investigated. Citation Format: Simon Kind, Carolina Castillo, Ria Uhlig, Natalia Gorbokon, Maximilian Lennartz, Sebastian Dwertmann Rico, Viktor Reiswich, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Franziska Büscheck, Till Clauditz, Christroph Fraune, Andrea Hinsch, Till Krech, Patrick Lebok, Stefan Steurer, Eike Burandt, Sarah Minner, Andreas Marx, Ronald Simon, Waldemar Wilczak, Guido Sauter, Anne Menz, Frank Jacobsen. KLK7 expression in human tumors: A tissue microarray study on 13,447 tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3302.

New Data on the Features of Skin Barrier in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.

Acne and insulin resistance: A systematic review and meta-analysis

To the Editor: Acne is more common in westernized societies, suggesting that environmental factors likely contribute to acne pathogenesis.1Cordain L. Lindeberg S. Hurtado M. Hill K. Eaton S.B. Brand-Miller J. Acne vulgaris: a disease of western civilization.Arch Dermatol. 2002; 138: 1584-1590Crossref PubMed Google Scholar Metabolic abnormalities may influence key factors in the development of acne, such as the proliferation of basal keratinocytes in the sebaceous-pilosebaceous unit and abnormal desquamation of follicular corneocytes.2Del Prete M. Mauriello M.C. Faggiano A. et al.Insulin resistance and acne: a new risk factor for men?.Endocrine. 2012; 42: 555-560Crossref PubMed Scopus (50) Google Scholar Therefore, we hypothesized that patients with acne would demonstrate higher levels of insulin resistance. In this systematic review and meta-analysis, we examined the relationship between insulin resistance and acne, as it may have important therapeutic and diagnostic implications, such as exploring insulin modifiers as an adjunctive acne treatment and screening acne patients for metabolic syndrome. PubMed and Embase were systematically searched for studies published prior to March 17, 2021 that evaluated insulin resistance in patients with acne. In PubMed and Embase (acne OR acne vulgaris) AND (insulin resistance OR diabetes OR blood glucose) were searched as Medical Subject Heading terms and keywords, respectively. Only clinical studies measuring values for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), a validated laboratory measure of insulin resistance, in acne patients and control subjects were included.3Muniyappa R. Madan R. Assessing insulin sensitivity and resistance in humans.in: Feingold K.R. Anawalt B. Boyce A. Endotext [Internet]. MDText.com, Inc, 2000Google Scholar Studies were excluded if they were unpublished, abstracts, not written in English, or included patients with polycystic ovarian syndrome in order to exclude hyperandrogenism as a potential confounding variable. Database searches yielded 136 unique results. Thirteen articles met inclusion criteria and were included in the analysis (Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/bfrm4wbdrz/2). The following data were extracted from each article: number of acne subjects, mean age of acne subjects, mean body mass index of acne subjects, acne severity, other acne qualifiers (postadolescent acne or treatment nonresponders), control subjects, mean HOMA-IR value in both acne and control groups, and quality assessment score (Supplementary Table 1, available via Mendeley at https://data.mendeley.com/datasets/bfrm4wbdrz/2). Meta-analysis compared the differences between acne and control patients. Hedges' g standardized mean difference between HOMA-IR values in acne patients and controls was calculated as the summary statistic. Results are reported from a random effects model. An I2 statistic was calculated to estimate heterogeneity across studies.4Egger M. Davey Smith G. Schneider M. Minder C. Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634Crossref PubMed Scopus (32351) Google Scholar Moderating variables were studied in a mixed-effects model. Statistical analyses were conducted with R statistical software (version 4.0.5) using the meta package.5Balduzzi S. Rücker G. Schwarzer G. How to perform a meta-analysis with R: a practical tutorial.Evid Based Ment Health. 2019; 22: 153-160Crossref PubMed Scopus (952) Google Scholar Acne patients had higher HOMA-IR values than controls (standardized mean difference = 0.60; 95% CI, 0.33-0.88; P < .001) (Supplementary Fig 2, available via Mendeley at https://data.mendeley.com/datasets/bfrm4wbdrz/2). Onset of acne in the postadolescent period, average age of participants, sex of participants, average body mass index, publication year, or quality score were not significant modifying variables in our model. There was heterogeneity between studies (P < .001), which was a limitation of our study. Publication bias was assessed visually using a funnel plot and quantitatively with Egger's regression test of asymmetry (Supplementary Fig 3, available via Mendeley at https://data.mendeley.com/datasets/bfrm4wbdrz/2). Although some asymmetry exists, the large effect size of study 13 appears to mitigate the asymmetry (P = .47). However, due to the small number of studies with a large variation in effect sizes and standard errors, we do not have enough evidence that publication bias does not exist in this study. Dermatologists should be aware of the potential relationship between acne and insulin resistance and consider referring acne patients to primary care for further evaluation. Early treatment of insulin resistance can prevent the development of diabetes and cardiovascular disease. None disclosed.

147 Cereus grandiflorus (Cactus) Flower Extract – A New Natural Skin Anti-Aging Ingredient with Multiple Properties

Skin aging signs are the result of the combination of several phenomena such as chronic exposure to exposome and the slowdown of repair processes and cell renewal. Identify an efficient natural ingredient, which can act both on the prevention of stress and on the stimulation of endogenous repair mechanisms, is a challenging target. Cereus grandiflorus belongs to the Cactaceae family (cactus). It is native from the desert regions of the Antilles, tropical America, and Mexico. Its flowers, sweet scented, bloom with white petals only at night during six hours. This medicinal flower is traditionally used to treat heart diseases. It is rich in sugars such as glucose, and fructose, amino acids, acids (citric, fumaric, malonic), alcaloids and flavonoids, which are known for their cosmetic properties. The present study aimed at evaluating the cosmetic benefits of this natural hydro- glycerin extract of Cereus grandiflorus flowers from Moroccan geographical origin. The measured cosmetic benefits of the ingredient were its antioxidant and anti-inflammatory properties as well the impact of the extract on keratinocyte metabolism and migration and corneocyte desquamation. In in vitro tests, this extract showed a broad-spectrum antioxidant action (Anti 1O2, OH°, anti O2°-, ORAC test). Moreover, it showed preventive effect on IL-6 release by keratinocytes in inflammatory state induced by phorbol 12-myristate 13-acetate (PMA). This reduction of IL-6 release suggests a potential anti-inflammatory effect. Using the Mito TrackerTM red and green FM, we showed that this extract increases keratinocyte and fibroblast mitochondrial activities. In an artificial keratinocyte wound healing test, the extract stimulated cells migration. Finally, we demonstrated that the extract decreases the stratum corneum cohesion in an ex vivo skin model, presenting a similar peeling effect as glycolic acid. Taken together, these results suggest that the Cereus grandiflorus extract appears as a valuable cosmetic ingredient towards skin protection, recovery and refinement of skin texture.

171 Successful dupilumab treatment for ichthyotic and atopic features of Netherton syndrome

Netherton syndrome (NS) is a rare, but severe autosomal-recessive ichthyosis syndrome characterized by a triad of ichthyosis, a hair shaft defect and atopic features. NS patients have a deficiency of serine protease inhibitor LEKTI in the stratum corneum, resulting in increased activity of serine proteases, accelerated desquamation of corneocytes and breakdown of the stratum corneum barrier, which accelerates percutaneous allergen sensitization. We performed a single-arm, prospective interventional study of the treatment with dupilumab, an interleukin (IL)-4 receptor α-antagonist that inhibits IL-4 and IL-13 signaling, for NS.

Antioxidant and skin anti-aging effects of the aqueous ethanol extract of Ginkgo biloba leaf: an in vitro study using HaCaT keratinocytes

Oxidative stress is considered a prime contributor to skin aging. Aged skin can be characterized by increased wrinkles and dry and dull appearance, which are associated with increased collagen degradation and inadequate desquamation, respectively. We investigated the antioxidant and skin anti-aging effects of a Ginkgo biloba leaf extract (GLE), an aqueous ethanol extract of Ginkgo biloba leaves, and the molecular mechanisms involved, using HaCaT keratinocytes. HaCaT cells were pretreated with GLE (0–15 μg/mL) and then treated with H2O2 (0.2 mM), and the cell viability and metalloproteinase 1 (MMP-1) protein level were measured. To investigate the mechanisms underlying the GLE’s effects, the cells were incubated with GLE, and then glutathione content, cell migration rate, and the levels of proteins, i.e., MMPs, Kallikrein-related peptidases (KLKs), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and mitogen-activated protein kinases, were measured. GLE pretreatment caused decreases in cytotoxicity and the level of MMP-1, a key enzyme that degrades collagen in dermis, induced by H2O2 in HaCaT cells. GLE (5–15 μg/mL) caused increases in glutathione content and HO-1 level in cells, which appeared to be associated with the increase in Nrf2, a principal transcription factor for the antioxidant response. GLE also increased keratinocyte migration, which might result from the increase in KLK-7, a key enzyme that degrades corneodesmosomes and thus stimulates desquamation of corneocytes in epidermis. GLE increased the phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, which might contribute to the antioxidant and skin anti-aging effects of GLE demonstrated in our results. Our results suggest that GLE may have skin anti-aging effects by protecting keratinocytes against excessive oxidative stress via stimulation of antioxidant response, reducing wrinkle formation via a decrease in MMP-1 expression, and stimulating desquamation via an increase in KLK-7 expression.

240 SerpinB12 is an intrinsic mesotrypsin inhibitor regulating corneocyte desquamation and enucleation

240 SerpinB12 is an intrinsic mesotrypsin inhibitor regulating corneocyte desquamation and enucleation

286 SerpinB12 is an intrinsic mesotrypsin inhibitor regulating corneocyte desquamation and denucleation

It is suggested that kallikrein-related peptidases (KLKs) are key players in corneocyte desquamation and this process is regulated by lympho-epithelial Kazal-type inhibitor (LEKTI). However, it is unclear how these proteases are activated and how activated KLKs are released from LEKTI in the upper cornified layer. Previously we reported cloning of a new PRSS3 gene product, keratinocyte-specific mesotrypsin from the cDNA library. It has been reported that mesotrypsin is insusceptible to intrinsic inhibitors. Moreover, we found that mesotrypsin effectively activated pro-KLK5 and pro-KLK7. Although LEKTI strongly inhibited KLKs, mesotrypsin was not suppressed by LEKTI but rather degraded them. Surprisingly, we isolated a novel inhibitor and identified it as serpinB12 (Another name is YUKOPIN). Thin skin, such as the eyelid, showed strong mesotrypsin staining, while serpinB12 staining was barely detectable. In contrast, footpad skin, which has a thick cornified layer, showed strong serpinB12 staining at the granular layer. We constructed skin equivalent models, in which serpinB12 was over-expressed or knocked-down. Cornified layers were increased and the epidermis became thicker in serpinB12 over-expression. When serpinB12 was down-regulated, the epidermal structure became very thin. Furthermore, we found that excessive over-expression of serpinB12 induced parakeratosis. Immunohistochemical study showed that serpinB12 was expressed in parakeratic area of diseased skin, such as psoriasis and atopic dermatitis. Our findings provided a new insight into the desquamation mechanisms, in which mesotrypsin and serpinB12 play critical roles. Moreover, our results suggest that serpinB12 would be involved in controlling the thickness of stratum corneum through mesotrypsin regulation, and excessive serpinB12 expression might be the cause of parakeratotic disease condition.

Systemic and skin-targeting beneficial effects of lycopene-enriched ice cream: A pilot study

The health-promoting dietary antioxidant lycopene has limited natural bioavailability, but lycopene-rich functional foods can improve its bioavailability. We assessed a new lycopene-enriched ice cream for systemic antioxidant effects and influence on morphological characteristics of facial skin surface in healthy volunteers. In a randomized crossover study, we used 4-wk dietary interventions with either control or lycopene-enriched ice cream. Samples of serum and residual skin surface components (RSSC) from facial skin were taken before interventions, at 2 wk, and at intervention end. Lycopene concentration, conventional blood biochemistry, and oxidative stress biomarkers comprising inflammatory oxidative damage and low-density lipoprotein peroxidase proteins were assessed in the serum. Lycopene-associated immunofluorescence, lipid droplet size, corneocyte desquamation, and microbial presence were measured in the RSSC. The results show that lycopene concentrations in the serum and skin steadily increased during lycopene-enriched ice cream consumption. Whereas we found no intervention-dependent changes in conventional biochemical parameters, both inflammatory oxidative damage and low-density lipoprotein peroxidase protein values significantly decreased by the end of intervention with lycopene-enriched ice cream, but remained unchanged during control ice cream consumption. Control ice cream significantly increased corneocyte desquamation and bacterial presence in the RSSC. These adverse effects, which could potentially predispose consumers to acne development, were absent when volunteers consumed lycopene-enriched ice cream. We concluded that lycopene-enriched ice cream is a new functional food with clear antioxidant properties. In addition, enrichment with lycopene may alleviate proinflammatory action of ice cream at the level of facial skin, thus decreasing diet-associated acne development risk in young consumers.

Infant Skin Barrier, Structure, and Enzymatic Activity Differ from Those of Adult in an East Asian Cohort.

Skin physiology is dynamically changing over the first years of postnatal life; however, ethnic variations are still unclear. The aim of this study was to characterize infant skin barrier function, epidermal structure, and desquamation-related enzymatic activity as compared to that of adult skin in an East Asian population. The skin properties of 52 infants (3-24 months) and 27 adults (20-40 years) were assessed by noninvasive methods at the dorsal forearm and upper inner arm. Transepidermal water loss and skin surface conductance values were higher and more dispersed for infants compared to adults. Infant skin surface pH was slightly lower than adult on the dorsal forearm. The infant SC and viable epidermis were thinner compared to adults with differences that were site-specific. Although the chymotrypsin-like activity for infant skin was comparable to adult level, the caseinolytic specific activity was significantly higher for the infant cohort. These observations indicate a differently controlled pattern of corneocyte desquamation in infants. In conclusion, structural and functional differences exist between infant and adult skin in the East Asian population pointing to dynamic maturation of the epidermal barrier early in life.

Continuous astaxanthin intake reduces oxidative stress and reverses age-related morphological changes of residual skin surface components in middle-aged volunteers

Oxidative stress accelerates skin aging, and dietary supplementation with antioxidants may alleviate it. Morphological analysis of the residual skin surface components (RSSCs) allows detecting age-related changes in corneocyte desquamation, microbial presence, and lipid droplet size. We hypothesized that continuous ingestion of carotenoid antioxidant astaxanthin (4 mg/d) for 4 weeks could influence RSCC morphology and evaluated RSSC samples taken from middle-aged subjects before and after this dietary intervention. The study included 31 volunteers (17 men and 14 women) over the age of 40. RSSC samples were collected from the surface of the facial skin at the beginning (day 0) and end (day 29) of the study. In addition, blood samples were taken on days 0, 15, and 29 for measuring plasma levels of malondialdehyde that allowed assessing systemic oxidative stress. The results demonstrated that plasma malondialdehyde consistently decreased during astaxanthin consumption (by 11.2% on day 15 and by 21.7% on day 29). The analysis of RSSC samples has revealed significantly decreased levels of corneocyte desquamation (P=.0075) and microbial presence (P=.0367) at the end of the study. These phenomena as well as a significant (P=.0214) increase in lipid droplet size were more strongly manifested among obese (body mass index >30 kg/m2) subjects. All described RSSC changes correspond to a shift toward characteristics of skin associated with a younger age. The results confirm our hypothesis by demonstrating that continuous astaxanthin consumption produces a strong antioxidant effect resulting in facial skin rejuvenation which is especially pronounced in obese subjects.

Autobronzants et bronzants artificiels

Practically all currently available self-tanning products have as their active ingredient dihydroxyacetone (DHA), which may or may not be combined with erythrulose, tyrosine derivatives, and occasionally a naphthoquinone. The resulting skin tone, which resembles a natural tan, is due to chemical combination of the DHA with amino acids in the skin through the Maillard reaction. Polymer pigments known as melanoidins are formed and are fixed in the stratum corneum, where they remain until corneocyte desquamation occurs. The colouring thus achieved is semi-permanent and is well tolerated by skin. While the formulation of such products is complex and their storage difficult, no other substances provide more satisfactory or more lasting results.

Complementary effect of hydroquinone and retinoic acid on corneocyte desquamation with their combination use

BackgroundRetinoic acid (RA) enhances skin-lightening capabilities of hydroquinone (HQ), at least in part, by facilitating desquamation which leads to increase penetration of HQ. The desquamation also affects skin irritation levels. The mechanism of RA-induced desquamation, however, has not been completely explored and no such data has been available for HQ uses. ObjectiveTo examine the role of HQ, RA, and their combination in the desquamation. MethodsPrimary cultured normal human keratinocytes, which were treated with HQ and/or RA in presence or absence of serine-specific inhibitor Kazal type5 (SPINK5)/lympho-epithelial Kazal-type-related inhibitor (LEKTI) knockdown or recombinant human SPINK5/LEKTI, and biopsied skin samples applied with HQ or RA were examined. Expression levels of corneodesmosin (CDSN), desmocollin1 (DSC1), kallikrein5 (KLK5), KLK7, and SPINK5/LEKTI, and proteolysis activity against extracted human skin epidermal protein were determined using time-course real-time PCR, Western blotting, ELISA, and immunofluorescence staining. ResultsHQ increased but RA decreased the synthesis of CDSN and DSC1. HQ reduced corneodesmosome degradation by the upregulation of SPINK5/LEKTI, whereas RA showed opposite results without upregulation of SPINK5/LEKTI. The combination of HQ and RA was close to the sum of the individual components. ConclusionsHQ reduced corneocyte desquamation. However, RA enhanced desquamation. The combination induced more desquamation than HQ but less than RA.

Morphological Characteristics of Residual Skin Surface Components Collected from the Surface of Facial Skin in Women of Different Age.

BackgroundProblems of skin aging and its prevention currently attract increasing attention with the growth of human life expectancy. The morphology of the stratum corneum (SC) is well known, but investigation of age-related changes of its structure is difficult in the absence of non-invasive sampling methods. The residual skin surface components (RSSC) that overlay the SC can be easily collected non-invasively.ObjectiveThe aim of this study was to examine morphology of RSSC samples collected from the surface of facial skin of healthy female volunteers of different age.MethodsRSSC samples were non-invasively collected from 53 adult female volunteers (22 aged in the range 18∼25 years and 31 aged in the range 50∼73 years). The samples were analysed microscopically.ResultsDistinct age-related changes were determined for lipid droplet size, corneocyte desquamation level and lipid crystal count. There was a significant (p=0.0006) decrease in lipid droplet size among older women. Similarly, significantly (p=0.0401) lower lipid crystal numbers were present in the older group. Conversely, corneocyte desquamation was significantly higher (p=0.0007) in older women. No age-related difference in microbial presence in the RSSC could be detected. Result patterns were generally similar to those previously found in male volunteers; however gender-related differences in the absolute values were revealed.ConclusionNon-invasively collected RSSC samples allow identifying age-related changes on facial skin surface. The results of this study highlight gender-dependence of distinct elements of age-associated impairment of epidermal barrier and can be employed for developing new approaches to prevent changes associated with skin aging.

Age-related differences in morphological characteristics of residual skin surface components collected from the surface of facial skin of healthy male volunteers.

Global increase of human longevity results in the emergence of previously ignored ageing-related problems. Skin ageing is a well-known phenomenon, but active search for scientific approaches to its prevention and even skin rejuvenation is a relatively new area. Although the structure and composition of the stratum corneum (SC), the superficial layer of epidermis, is well studied, relatively little is known about the residual skin surface components (RSSC) that overlay the surface of the SC. The aim of this study was to examine morphological features of RSSC samples non-invasively collected from the surface of human facial skin for the presence of age-related changes. Residual skin surface component samples were collected by swabbing from the surface of facial skin of 60 adult male volunteers allocated in two age groups: 34 subjects aged in the range 18-32 years and 26 subjects aged in the range 58-72 years. The collected samples were analysed microscopically: the size of the lipid droplets was measured; desquamated corneocytes and lipid crystals were counted; and microbial presence was assessed semi-quantitatively. Age-related changes were revealed for all studied components of the RSSC. There was a significant (P = 0.0126) decrease in the size of lipid droplets among older men. Likewise, significantly (P = 0.0252) lower numbers of lipid crystals were present in this group. In contrast, microbial presence in the RSSC was significantly (P = 0.0019) increased in the older group. There was also a trend towards more abundant corneocyte desquamation among older men, but the difference has not reached statistical significance (P = 0.0636). Non-invasively collected RSSC samples present an informative material for studying age-related changes on the surface of the SC of human facial skin. The results of this study confirm earlier observations regarding age-associated decline of the efficiency of the epidermal barrier and can be used for testing new approaches to skin ageing prevention.

Keratolysis exfoliativa

Keratolysis exfoliativa (KE) is a palmoplantar eruption of air-filled bullae on an erythematous base, which results in lamellar peeling with hallmark superficial collarettes of scale. It is distinct from other diseases of volar skin, such as dyshidrosis, contact dermatitis, tinea, epidermolysis bullosa, and acral skin peeling. We present a 55-year-old woman with extensive disease on the hands and feet, who failed to respond to standard topical therapy but showed a marked dose-response improvement with the use of oral acitretin. Recent histopathologic and molecular studies have linked KE to premature corneo-desmosomal disruption. Acitretin has previously been used to treat diseases of abnormal corneocyte desquamation, for example Netherton's disease. To the best of our knowledge, this report is the first that documents the efficacy of the use of systemic acitretin in KE.