Role In Skin Barrier Function 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.

Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

The stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.

A modified protocol for studying filaggrin degradation using a reconstructed human epidermis model under low and high humidity.

Filaggrin (FLG) is an essential protein that plays a vital role in maintaining skin barrier function and moisture levels, allowing the skin to adapt to dry environments. However, the precise temporal dynamics of FLG metabolism in the human epidermis remain poorly understood, and suitable tools to study these time-dependent effects are currently lacking. To investigate the molecular mechanisms and time course of FLG metabolism and skin barrier function under high- and low-humidity conditions, utilizing a reconstructed epidermis model. EpiSkin specimens cultured under humid or dry conditions for varying durations (2-48 h) were compared by assessing FLG degradation and skin barrier formation using immunofluorescence staining and western blotting. Under conditions of low humidity, the proteolysis of FLG in EpiSkin increased between 4 and 12 h and was accompanied by elevated levels of cysteine-aspartic protease (caspase)-14. The expression of peptidyl arginine deiminase 1 and calpain 1 also increased at 4 h. However, after 24 h, the expression of these three FLG-degrading proteins significantly decreased. Conversely, the levels of pyrrolidone-5-carboxylic acid and urocanic acid initially decreased at 2 h and then increased between 12 and 24 h. Additionally, the expression of skin barrier proteins, such as FLG, transglutaminase 5, loricrin and zonula occludens-1, decreased starting from 12 h. Notably, epidermal cell viability and activity were also inhibited. We propose a reliable and ethical model to study the temporal dynamics of FLG metabolism and its role in skin barrier function. Using a commercially reconstructed epidermis to mimic dry skin formation obviates the need for animal and human testing.

Lipidomics Reveals the Effects of Detergents on Skin Surface Lipids in Young Adults

Background: Detergent is a chemical product commonly used in people’s daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage. Methods: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. Results: The skin barrier function of subjects’ hands was impaired after exposure to detergent (TEWL value increased, p < 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids. Conclusion: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value.

A sequential tape stripping approach for the assessment of the impact of personal cleansing products on the stratum corneum surface layers' acid mantle properties and antimicrobial defense.

Stratum corneum (SC) plays a critical role in skin barrier function for protection and defense in nature. The acidic skin pH, which is also known as the acid mantle, is very important in fighting against outer environmental threats, especially, bacteria. Furthermore, recent research has shown that the transient bacteria could potentially penetrate into deeper layer of the SC down to a few micrometers while posing an additional threat to the deeper layers of the skin. To develop a sequential tape stripping method for assessing the impact of personal cleansing product on the SC surface layers' acid mantle properties and antimicrobial defense against transient bacteria. Fifty-five subjects were recruited. High pH soap-based Product 1 and low pH synthetic surfactant-based Product 2 were applied on the left and right forearms of each subject. Sequential tape stripping was performed on the same spots to access multiple layers of the skin SC. Both antimicrobial defense property and skin pH of different skin layers were evaluated at baseline and 12 h after treatment. The skin's antimicrobial defense was significantly higher 12 h after treatment of the low pH Product 2 as compared to the treatment of high pH Product 1. In fact, this trend was consistent across all three skin layers (Layer 1 to Layer 3) as measured in this study (p < 0.01). Furthermore, the skin surface pH of Layer 1 and Layer 3 were also lower 12 h after the treatment of low pH Product 2 as compared to that of the high pH Product 1 (p < 0.01). The results of this investigation demonstrated the benefits of 12-h long lasting and deeper protection of SC acid mantle properties and antimicrobial defense using a low pH skin cleansing product as compared to a high pH product.

Delineating the relationship of Vitamin D binding protein (VDBP) genetic variants in exon 11 with serum Vitamin D levels in Atopic Dermatitis

BackgroundAtopic Dermatitis (AD) is a multifactorial cutaneous disorder with a profound impact on the quality of life of patients. In terms of AD etiology, vitamin D deficiency is gaining relevance owing to its role in skin barrier function and the keratinocyte proliferation process. This study seeks to ascertain the role of Vitamin D Binding Protein (VDBP) genetic variants (rs7041 and rs4588) in determining serum Vitamin D levels in AD patients as well as to investigate their role in AD susceptibility and severity. MethodsAn aggregate of 210 subjects including 100 AD cases and 110 matched controls were genotyped for VDBP SNPs by PCR-RFLP. The severity of AD was evaluated using the SCORAD index. Total IgE and Vitamin D levels were estimated by ELISA and chemiluminescence, respectively. ResultsThe CC genotype of rs4588 was linked to higher Vitamin D levels whereas the AA genotype was linked to lower levels of Vitamin D (p = 0.02). Besides, mean serum Vitamin D levels were less in females (p = 0.02), older patients (p = 0.01), and with a severe form of the disease (p = 0.01). Overall, the genotypic and allelic frequency of both SNPs showed no significant difference among cases and controls. ConclusionThis study reveals that VDBP SNP rs4588 could be a possible modulator of serum Vitamin D levels and hence bears important clinical implications in AD.

Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.

Psoriasis is characterized by intense pruritus, with a subset of individuals with psoriasis experiencing thermal hypersensitivity. However, the pathophysiology of thermal hypersensitivity in psoriasis and other skin conditions remains enigmatic. Linoleic acid is an omega-6 fatty acid that is concentrated in the skin, and oxidation of linoleic acid into metabolites with multiple hydroxyl and epoxide functional groups has been shown to play a role in skin barrier function. Previously, we identified several linoleic acid‒derived mediators that were more concentrated in psoriatic lesions, but the role of these lipids in psoriasis remains unknown. In this study, we report that two such compounds-9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate-are present as free fatty acids and induce nociceptive behavior in mice but not in rats. By chemically stabilizing 9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate through the addition of methyl groups, we observed pain and hypersensitization in mice. The nociceptive responses suggest an involvement of the TRPA1 channel, whereas hypersensitive responses induced by these mediators may require both TRPA1 and TRPV1 channels. Furthermore, we showed that 9,10,13-trihydroxy-octadecenoate‒induced calcium transients in sensory neurons are mediated through the Gβγ subunit of an unidentified G-protein coupled receptor (GPCR). Overall, mechanistic insights from this study will guide the development of potential therapeutic targets for the treatment of pain and hypersensitivity.

Composition and function of the skin microbiota were altered of red leg syndrome in cultured bullfrog (Rana catesbeiana)

Skin microbiota play an important role in skin barrier function and are associated with host health. The study of the skin microbiota is beneficial for managing disease with skin microbiota. Bullfrog (Rana catesbeiana) is an important cultured animal. Bacterial diseases like red leg syndrome (RLS) often occur in bullfrog cultured and cause huge economic losses around the world. However, the appearance of RLS is unknown. Here we compare the skin microbiota of RLS bullfrog and healthy bullfrog by 16 S rRNA microbiome profiles. The bacterial community diversity of bullfrog skin was significantly different between RLS and healthy group. Proteobacteria, Bacteroidota, Firmicutes were the most abundant phyla in bullfrog skin. Compared with healthy bullfrogs, RLS bullfrogs had high abundance of Acinetobacter, Chryseobacterium, Elizabethkingia, Flavobacterium and Streptococcus in skin microbiota, but the relative abundance of Cetobacterium, Bacteroides and Shewanella was overrepresented in the RLS bullfrog. The Tax4Fun function prediction showed that the relative abundance of genes associated with Nucleotide metabolism, Translation, Nucleotide metabolism, Translation, Glycan biosynthesis and metabolism exhibited was significantly higher in RLS bullfrogs. The results suggested that the RLS significantly changed the composition and predictive function of the skin bacterial community in cultured bullfrogs. This study is the first to report on the relationship between skin microbiota and red leg syndrome of bullfrog, which can expand our understanding of bacterial communities in bullfrog farming from the perspective of microbial ecology and help prevent and manage RLS in bullfrog farming.

Studying the effects of suberythemal UV doses on the human stratum corneum by in vivo confocal Raman spectroscopy

The stratum corneum (SC) plays an important role in skin barrier function. It acts as a protective barrier against water loss, eliminates foreign substances and micro-organisms and acts against harmful effects of UVR. Our aim was to study the impact of suberythemal doses of UVA and UVB exposure on the molecular structure, organization and barrier function of the SC by following different Raman descriptors. Twenty female volunteers, aged 20-30 years, with healthy skin were enrolled. Doses of 95 mJ/cm²UVA and 15 mJ/cm²UVB were applied to volunteers’ forearms. In vivo Raman measurements were performed at irradiated and control regions. The impact of UVA and UVB irradiation was observed following several Raman descriptors, i.e. the ratio of vasymCH2/vsymCH2 (2885 cm-1/2850 cm-1) corresponding to the organizational order of the lipid bilayer. Water content and mobility descriptors were obtained by calculating vOH/vCH ratio. Finally, protein secondary structure was evaluated based on the 1670 cm-1/1650 cm-1ratio related to β sheets and α helices, respectively. UVA induced a loosening of the lateral packing of lipids immediately after irradiation. In contrast, delayed impact caused a tightening of the lipid barrier, an increase in water content -mainly in the unbound water fraction and a higher relative amount of β sheets in SC proteins. Overall, these observations may explain the thickening of the SC observed in previous studies. A UVB dose of 15 mJ/cm²was apparently below the threshold necessary to induce significant changes despite the trends observed in this study.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3months of age and throughout infancy. FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12months of age. FLG mutations were observed in 166 (9%) infants. At 3months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3gm-2 h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P<0·001]. At 6months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P<0·01], and at 3 and 6months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P=0·002 and OR 2·44, 95% CI 1·51-3·95; P<0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P=0·028 and OR 1·74, 95% CI 1·17-2·57; P=0·005). FLG mutations were associated with eczema and AD in infancy. FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6months.

Natural moisturizing factors in children with and without eczema: Associations with lifestyle and genetic factors.

Filaggrin-derived natural moisturizing factors (NMF) play an important role in skin barrier function and in atopic dermatitis (AD). Its deficiency is associated with dry skin and increased surface pH. Studies on childhood environmental exposures and associations with NMF levels are scarce. To investigate previous exposures and genetic factors and their associations with NMF levels in young children. In a case-control study nested in a prospective birth cohort (Odense Child Cohort), 169 healthy controls (HC) and 99 children with AD were included consecutively at the age of 7 years based on previous responses from questionnaires administered at 18 months, 3 years and 5 years, pertaining to past medical history, including allergy-specific questions. NMF levels were measured via a stratum corneum tape-stripping technique, genotyping for filaggrin (FLG) gene variants was performed and data on external exposures, including usage of moisturizer and topical steroids, antibiotics and early pet exposures, were obtained from questionnaires. Natural moisturizing factors levels were significantly lower in AD participants compared to HC (P < 0.001). This significance persisted after stratifying for AD subgroups of present AD, current AD during the last year and previous AD (P < 0.001, P = 0.039, P = 0.009 respectively). There was a significant association between NMF and FLG genotype (P = 0.016, P = 0.002 for HC, AD respectively). NMF levels were negatively correlated with early age moisturizer use (<18 months, P = 0.001) in HC but not significant in AD. We found decreased levels of NMF with early moisturizer use and a genetic influence of the FLG variant on these levels. NMF was decreased in the AD subgroup with previous AD compared with HC, which could suggest the persistence of a Th2 cytokine milieu suppressing these levels.

Structural characterization of plant glucosylceramides and the corresponding ceramides by UHPLC-LTQ-Orbitrap mass spectrometry

Ceramides (CERs) play a major role in skin barrier function and direct replacement of depleted skin CERs, due to skin disorder or aging, has beneficial effects in improving skin barrier function and skin hydration. Though, plants are reliable source of CERs, absence of economical and effective method of hydrolysis to convert the dominant plant sphingolipid, glucosylceramides (GlcCERs), into CERs remains a challenge. This study aims at exploring alternative GlcCERs sources and chemical method of hydrolysis into CERs for dermal application. GlcCERs isolated from lupin bean (Lupinus albus), mung bean (Vigna radiate) and naked barley (Hordium vulgare) were identified using ultra high performance liquid chromatography hyphenated with atmospheric pressure chemical ionization - high resolution tandem mass spectrometer (UHPLC/APCI-HRMS/MS) and quantified with validated automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method. Plant GlcCERs were hydrolyzed into CERs with mild acid hydrolysis (0.1 N HCl) after treating them with oxidizing agent, NaIO4, and reducing agent, NaBH4. GlcCERs with 4,8-sphingadienine, 8-sphingenine and 4-hydroxy-8-sphingenine sphingoid bases linked with C14 to C26 α-hydroxylated fatty acids (FAs) were identified. Single GlcCER (m/z 714.5520) was dominant in lupin and mung beans while five major GlcCERs species (m/z 714.5520, m/z 742.5829, m/z 770.6144, m/z 842.6719 and m/z 844.56875) were obtained from naked barley. The GlcCERs contents of the three plants were comparable. However, lupin bean contains predominantly (> 98 %) a single GlcCER (m/z 714.5520). Considering the affordability, GlcCER content and yield, lupin bean would be the preferred alternative commercial source of GlcCERs. CER species bearing 4,8-sphingadienine and 8-sphingenine sphingoid bases attached to C14 to 24 FAs were found after mild acid hydrolysis. CER species with m/z 552.4992 was the main component in the beans while CER with m/z 608.5613 was dominant in the naked barley. However, CERs with 4-hydroxy-8-sphingenine sphingoid base were not detected in UHPLC-HRMS/MS study suggesting that the method works for mainly GlcCERs carrying dihydroxy sphingoid bases. The method is economical and effective which potentiates the commercialization of plant CERs for dermal application.

Formulation of bicelles with cholesterol using a semi-spontaneous method

Stratum corneum intercellular lipids play an important role in skin barrier function and are therefore considered useful in pharmaceutical and cosmetics products. In this study, we formulated cholesterol (Cho), the main component of intercellular lipids, into bicelles using a semi-spontaneous method, with the ultimate aim of extending the utility of bicelles in cosmetics. Bicelles are disk-shaped structures in which the planar part comprises long-chain phospholipids and the rims comprise short-chain phospholipids. We used soybean lecithin (SL) and nonionic surfactants (NS) to formulate Cho into bicelles using a semi-spontaneous method. Cho was successfully formulated into bicelles using poly(oxyethylene) cholesteryl ether (with an average of 10 ethylene oxide units, ChEO10) as the NS. We identified the boundaries of the bicelle region in the SL-Cho-ChEO10 system by measuring particle sizes. A bicelle region was formed up to around a maximum mixing ratio of 10wt% Cho, representing a mole fraction (mol%) of approximately 33. Phase changes in the system were observed. Comparison of poly(oxyethylene) cholesteryl ethers containing an average of 10 or 20 (ChEO20) ethylene oxide units revealed that the size of the hydrophilic group affects both the bicelle formation region and the mixing ratio of Cho. We analyzed the state of the SL-Cho-ChEO10 bicelles by differential scanning calorimetry and found that samples containing only phospholipid (SL/Ch/ChEO10 = 1/0/0) provided an endothermic peak between 50 and 55 °C, corresponding to the gel-liquid crystal transition point of the phospholipid. In contrast, the bicelle regions (SL/Cho/ChEO10 = 0.4/0/0.6 and 0.37/0.05/0.58) lacked a gel liquid crystal transition point and a liquid-ordered state was induced by Cho or ChEO10. This indicates that these bicelles are highly stable towards thermal changes.

Skin Microbiome as Years Go By.

The skin microbial communities, i.e., the microbiota, play a major role in skin barrier function so must remain dynamic to adapt to the changes in the niche environment that occur across the different body sites throughout the human lifespan. This review provides an overview of the major alterations occurring in the skin microbiome (microbial and genomic components) during the various stages of life, beginning with its establishment in the first weeks of life through to what is known about the microbiome in older populations. Studies that have helped identify the factors that most influence skin microbiome function, structure, and composition during the various life stages are highlighted, and how alterations affecting the delicate balance of the microbiota communities may contribute to variations in normal physiology and lead to skin disease is discussed. This review underlines the importance of improving our understanding of the skin microbiome in populations of all ages to gain insights into the pathophysiology of skin diseases and to allow better monitoring and targeted treatment of more vulnerable populations.

Role of Tight Junctions and Their Protein Expression in Atopic Dermatitis

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.

Association of dry skin with intercellular lipid composition of stratum corneum after erlotinib administration.

Erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, causes skin disorders such as dry skin, which impairs the skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function; therefore, this study aimed to investigate the relationship between erlotinib-related dry skin and changes in the intercellular lipid composition and structure of the SC. Overall, 21 patients with non-small lung cancer were enrolled in this study. All patients received 150mg/day erlotinib orally. A SC sample of each patient was collected from the inner forearm using the tape stripping method on days 0, 7, 14, 28, and 56 after erlotinib administration. The intercellular lipid components of ceramide (CER), free fatty acid (FFA), and cholesterol sulfate (CS) in samples extracted from the tape were analyzed using liquid chromatography/time-of-flight/mass spectrometry. SC samples from six healthy subjects were collected as controls on days 0, 28 and 56 and analyzed similarly. Although total CER and FFA levels were not changed after erlotinib administration, the levels of CER subclasses [AP] and [AH] and hydroxy FFA, which are structural components of CER subclass [A], decreased. In contrast, the CS levels increased after erlotinib administration. Moreover, higher CS levels in the SC correlated with the clinical condition of dry skin. No changes were observed in the SC lipid composition in healthy subjects. Erlotinib-related dry skin was associated with a higher CS level in the SC.

A Survey of Turkish Nurses' Knowledge of Incontinence-Associated Dermatitis.

The purpose of this study was to determine the knowledge of incontinence-associated dermatitis (IAD) among nurses working in intensive care units. Descriptive study. The study was conducted in 6 intensive care units of a 550-bed academic research hospital in Turkey. Licensed practical and registered nurses with a minimum of a Bachelor of Science in Nursing degree employed full-time on these units were invited to participate. The survey consisted of statements that examined the demographic characteristics (14 questions) and knowledge levels (59 statements) of the nurses. For each statement, nurses were required to mark only one of the following options: "correct," "incorrect," or "no knowledge." Data were collected from July to September 2016. The Shapiro-Wilk test, Mann-Whitney U test, Kruskal-Wallis H test, post hoc multiple comparison test, and Spearman's correlation coefficient were used to analyze the data. Of the 126 RNs who participated in the study, 46.83% (n = 59) had an undergraduate degree in nursing. The majority (29.37%) practiced in gastroenterology surgery and urology intensive care units. The mean knowledge score was 33.05 ± 10.16 (min = 0, max = 59). The most correctly answered statement (94.44%; n = 119) was "The pH of the skin plays a role in skin barrier function." The statement with the most incorrect or "no knowledge" answers (96.03%; n = 120) was "The natural moisturizing factor found in the structure of corneocytes helps the skin to maintain its oil levels." Based on correctly answered statements, we found knowledge levels of the prevention and treatment of IAD were higher among nurses with a master of science degree in nursing (40.67 ± 4.32) and lower among licensed practical nursing (29.12 ± 10.08) (P < .05). In this study, knowledge of the nurses on identification, prevention, and treatment of IAD was low. Comprehensive basic nursing education and in-service training programs on IAD are recommended.

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency

Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.

Genetic variants of filaggrin are associated with occupational dermal exposure and blood DNA alterations in hairdressers

Hairdressers are exposed to high levels of chemicals, including possible carcinogens. For dermal exposure, the skin protects against the uptake of chemicals and the protein filaggrin (encoded by FLG) has a key role in skin barrier function. This study investigated if variants of FLG previously linked to impaired skin barrier function, i.e. null mutations and copy number variation (CNV) alleles (CNV10), are associated with cancer-related DNA changes. Blood and questionnaire data were collected from hairdressers (n = 295) and controls (n = 92). Exposure to aromatic amines was measured as hemoglobin adducts by gas chromatography tandem mass spectrometry. DNA from peripheral blood was used to test for FLG null mutations and CNV (10, 11, or 12 repeats), telomere length, and methylation of selected cancer-related genes. Hairdressers had a lower frequency of FLG null mutations (4.1 vs. 7.6%, P = 0.18) and CNV10 (43.2 vs. 56%, P = 0.0032) than controls. In hairdressers, CNV10 carriers had a decreased risk of high ortho-toluidine adducts in blood compared with non-carriers (odds ratio, OR = 0.49, 95% CI = 0.30–0.81). Further, telomere length was shorter for carriers of any FLG null allele (β = −0.18, 95% CI = −0.31 to −0.044) and CNV10 carriers (β = −0.054, 95% CI = −0.11 to −0.00051, linear regression adjusted for age, passive smoking, residence, and education) compared to non-carriers. Carriers of any FLG null allele showed higher methylation of the cyclin-dependent kinase inhibitor 2A gene CDKN2A (OR = 6.26, CI = 1.13–34.7), but not of the other genes analyzed. These associations were not found among the controls. Our study showed that the frequency of FLG CNV10 was lower among hairdressers than controls, which may indicate a healthy worker selection. Moreover, FLG null and CNV10 were associated with cancer-related DNA changes in hairdressers, which may influence their risk of cancer.

Determination of fatty acid and sphingoid base composition of eleven ceramide subclasses in stratum corneum by UHPLC/scheduled-MRM.

Ceramides play a key role in skin barrier function in homeostatic and pathological conditions and can be sampled non-invasively through stratum corneum collection. To develop a novel UHPLC/Scheduled MRM method for the identification and relative distribution of eleven classes of ceramides, which are separated by UHPLC and determined by their specific retention times. The precise composition of the fatty acid and sphingoid base parts of each individual ceramide is determined via mass fragmentation. More than 1000 human and pig ceramides were identified. Three human and minipig ceramide classes, CER[AS], CER[NS] and CER[EOS] have been investigated in depth. Sphingoid bases were characterized by a prevalence of chain lengths with sizes from C16 to C22, whereas fatty acids were mainly observed in the range of C22-C26. Overall, the ceramide profiles between human and minipig stratum corneum were similar. Differences in the CER[AS] and CER[NS] classes included a more homogeneous distribution of fatty acids (16-30 carbon atoms) in minipig, whereas in human longer fatty acid chains (> 24 carbon atoms) predominated. The method will be useful for the analysis of healthy and pathological skin in various specie, and the measurement of the relative distribution of ceramides as biomarkers for pharmacodynamic studies.