Granzyme B inhibition reduces autoantibody-induced dermal-epidermal separation in an ex vivo model of epidermolysis bullosa acquisita.

The pemphigoid disease epidermolysis bullosa acquisita (EBA) is an autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7), immune cell infiltrates at the dermal-epidermal junction and subepidermal blistering. Proteases, particularly granzyme B (GzmB), have been established as therapeutic targets for the treatment of EBA and other pemphigoid diseases. We investigated the impact of the novel GzmB inhibitor SNT-6935 on anti-COL7 IgG-induced subepidermal blistering in a well-established EBA ex vivo model. Our findings demonstrate that pharmacological targeting of GzmB with its selective inhibitor SNT-6935 significantly reduced autoantibody-induced dermal-epidermal separation in human skin cryosections. Interestingly, treatment of skin cryosections with recombinant human GzmB alone did not cause dermal-epidermal separation, suggesting that additional mechanisms alongside GzmB are required for tissue damage in EBA. In conclusion, our study highlights the significant contribution of GzmB to the pathogenesis of EBA and supports the notion of GzmB as a therapeutic target in EBA and other pemphigoid diseases.

The use of ectopic volar fibroblasts to modify skin identity.

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 (KRT9) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts' capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.

The transcription factor RUNT-like regulates pupal cuticle development via promoting a pupal cuticle protein transcription.

Holometabolous insects undergo morphological remodeling from larvae to pupae and to adults with typical changes in the cuticle; however, the mechanism is unclear. Using the lepidopteran agricultural insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the transcription factor RUNT-like (encoded by Runt-like) regulates the development of the pupal cuticle via promoting a pupal cuticle protein gene (HaPcp) expression. The HaPcp was highly expressed in the epidermis and wing during metamorphosis and was found being involved in pupal cuticle development by RNA interference (RNAi) analysis in larvae. Runt-like was also strongly upregulated in the epidermis and wing during metamorphosis. Knockdown of Runt-like produced similar phenomena, a failure of abdomen yellow envelope and wing formation, to those following HaPcp knockdown. The insect molting hormone 20-hydroxyecdysonen (20E) upregulated HaPcp transcription via RUNT-like. 20E upregulated Runt-like transcription via nuclear receptor EcR and the transcription factor FOXO. Together, RUNT-like and HaPCP are involved in pupal cuticle development during metamorphosis under 20E regulation.

Comparison of facial skin ageing in healthy Asian and Caucasian females quantified by in vivo line-field confocal optical coherence tomography 3D imaging.

BACKGROUND: Quantitative biomarkers of facial skin aging were investigated in 109 healthy Asian female volunteers, aged 20 to 70 years. MATERIALS AND METHODS: In vivo 3D Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging, enhanced by Artificial Intelligence (AI)-based quantification algorithms, was utilized to compute various metrics, including stratum corneum thickness (SC), viable epidermal (VE) thickness, and Dermal-Epidermal Junction (DEJ) undulation along with cellular metrics for the temple, cheekbone, and mandible. RESULTS: Comparison with data from a cohort of healthy Caucasian volunteers revealed similarities in the variations of stratum corneum and viable epidermis layers, as well as cellular shape and size with age in both ethnic groups. However, specific findings emerged, such as larger, more heterogeneous nuclei in both layers, demonstrated by an increase in nuclei volume and their standard deviation, and increased network atypia, all showing significant age-related variations. Caucasian females exhibited a flatter and more homogeneous epidermis, evidenced by a decreased standard deviation of the number of layers, and a less dense cellular network with fewer cells per layer, indicated by a decrease in cell surface density. CONCLUSION: Ethnicity-wise comparisons highlighted distinct biological features specific to each population. Asian individuals showed significantly higher DEJ undulation, higher compactness, and lower cell network atypia compared to their Caucasian counterparts across age groups. Differences in stratum corneum and viable epidermal thickness on the cheekbone were also significant. LC-OCT 3D imaging provides valuable insights into the aging process in different populations and underscores inherent biological differences between Caucasian and Asian female volunteers.

Phosphodiesterase 4 is overexpressed in keloid epidermal scars and its inhibition reduces keratinocyte fibrotic alterations.

BACKGROUND: Epidermal remodeling and hypertrophy are hallmarks of skin fibrotic disorders, and keratinocyte to mesenchymal (EMT)-like transformations drive epidermis alteration in skin fibrosis such as keloids and hypertrophic scars (HTS). While phosphodiesterase 4 (PDE4) inhibitors have shown effectiveness in various fibrotic disorders, their role in skin fibrosis is not fully understood. This study aimed to explore the specific role of PDE4B in epidermal remodeling and hypertrophy seen in skin fibrosis. METHODS: In vitro experiments examined the effects of inhibiting PDE4A-D (with Roflumilast) or PDE4B (with siRNA) on TGFß1-induced EMT differentiation and dedifferentiation in human 3D epidermis. In vivo studies investigated the impact of PDE4 inhibition on HOCl-induced skin fibrosis and epidermal hypertrophy in mice, employing both preventive and therapeutic approaches. RESULTS: The study found increased levels of PDE4B (mRNA, protein) in keloids > HTS compared to healthy epidermis, as well as in TGFß-stimulated 3D epidermis. Keloids and HTS epidermis exhibited elevated levels of collagen Iα1, fibronectin, αSMA, N-cadherin, and NOX4 mRNA, along with decreased levels of E-cadherin and ZO-1, confirming an EMT process. Inhibition of both PDE4A-D and PDE4B prevented TGFß1-induced Smad3 and ERK1/2 phosphorylation and mesenchymal differentiation in vitro. PDE4A-D inhibition also promoted mesenchymal dedifferentiation and reduced TGFß1-induced ROS and keratinocyte senescence by rescuing PPM1A, a Smad3 phosphatase. In vivo, PDE4 inhibition mitigated HOCl-induced epidermal hypertrophy in mice in both preventive and therapeutic settings. CONCLUSIONS: Overall, the study supports the potential of PDE4 inhibitors, particularly PDE4B, in treating skin fibrosis, including keloids and HTS, shedding light on their functional role in this condition.

Cuidados com a pele no inverno

Quem não gosta de um banho quentinho no inverno, não é mesmo? É tão reconfortante! Mas cuidado, o banho quente pode ser um vilão para saúde da nossa pele. O #AtivaIdade de hoje traz dicas para cuidar do maior órgão do corpo, principalmente em tempo seco e frio.

A importância de cuidar da pele na terceira idade

Changes in epidermal thickness and their correlation with clinical characteristics in patients with vitiligo.

Vitiligo is an autoimmune disorder characterized by epidermal melanocyte damage, with the typical clinical manifestation of white patches of skin. Keratinocytes, which work in concert with melanocytes to maintain the structural and functional integrity of the skin, are implicated in the progression of vitiligo. Recent studies have reported abnormal keratinocyte proliferation and epidermal thickening in some patients with vitiligo; however, the relationship between these changes and the clinical characteristics of vitiligo remains unclear. We assessed the changes in epidermal thickness in patients with vitiligo and their correlation with clinical characteristics. Compared to the non-lesional skins, the stratum corneum, viable epidermis, and full epidermis in the lesional skins were all significantly thicker. The thickness of the stratum corneum in the head, neck, and trunk was greatly lower than that in the extremities. The thickness of the stratum corneum in the sun-exposed area was higher than that in the sun-protected area, whereas the thickness of the viable epidermis decreased. In conclusion, our study found that the epidermis in the lesional skins of patients with vitiligo was significantly thickened, especially in the sun-exposed areas and extremities.

Effects of eczema calming lotion on the stratum corneum in atopic dermatitis: Corneodesmosin and intercellular lipid lamellae.

OBJECTIVE: Atopic dermatitis (AD) is characterized by compositional and structural changes to the skin at lesional sites. Alteration to the levels and organization of both protein and lipid components are associated with disease status and lead to impaired barrier and hydration. Corneodesmosin (CDSN) and the arrangement and length of the intercellular lipid lamellae (ICLL) are altered in disrupted skin states. The aim of this research was to profile the distribution of CDSN and the ICLL in the stratum corneum (SC) at lesional and non-lesional sites in AD-prone skin and to investigate the impact of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. METHODS: An IRB-approved study was conducted with participants with active AD. From a small subset of participants, tape strips were collected from lesional and non-lesional sites on the arm, prior to and after twice daily application, over 4 weeks of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Fluorescent antibody staining was used to investigate the distribution of CDSN. Transmission electron microscopy (TEM) was used to characterize the ICLL. RESULTS: The distribution/coverage of CDSN was similar between lesional and non-lesional sites at baseline; application of the lotion resulted in a more defined honeycomb/peripheral distribution. Normalized ICLL (nICLL) was lower in baseline samples from lesional sites relative to non-lesional sites. Application of the lotion increased this parameter by the end of the study at all sites. CONCLUSION: The eczema calming lotion containing petroleum jelly, fatty acids and colloidal oatmeal provided changes in corneodesmosomal proteins distribution and ICLL, consistent with improvements in corneocyte maturation and improved barrier function in the skin of individuals with atopic dermatitis.

OBJECTIF: La dermatite atopique (DA) est caractérisée par des modifications de la composition et de la structure de la peau au niveau des sites lésionnels. L'altération des taux et de l'organisation des composants protéiques et lipidiques est associée au statut de la maladie, et entraîne une altération de la barrière et de l'hydratation. La cornéodesmosine (CDSN), et la disposition et la longueur des lamelles lipidiques intercellulaires (LLIC) sont altérées dans les états cutanés perturbés. L'objectif de cette étude était d'établir le profil de la distribution de la CDSN et des LLIC dans la couche cornée (CC) au niveau des sites lésionnels et non lésionnels dans la peau sujette à la DA, et d'étudier l'impact d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. MÉTHODES: Une étude approuvée par un CPP a été menée auprès de participants atteints de DA active. Dans un petit sous­ensemble de participants, des bandes adhésives ont été prélevées sur des sites lésionnels et non lésionnels du bras, avant et après l'application deux fois par jour pendant 4 semaines d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. Une coloration par anticorps fluorescents a été utilisée pour étudier la distribution de la CDSN. La microscopie électronique en transmission (MET) a été utilisée pour caractériser les LLIC. RÉSULTATS: La distribution/couverture de la CDSN était similaire entre les sites lésionnels et non lésionnels à l'entrée dans l'étude; l'application de la lotion a entraîné une distribution en nid d'abeille/périphérique plus définie. Le taux normalisé de LLIC (LLICn) était plus faible dans les échantillons prélevés à l'entrée dans l'étude au niveau des sites lésionnels par rapport aux sites non lésionnels. L'application de la lotion a augmenté ce paramètre à la fin de l'étude pour tous les sites. CONCLUSIONS: La lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale a entraîné des changements dans la distribution des protéines cornéodesmosomales et des LLIC, ce qui correspond à des améliorations de la maturation des cornéocytes et de la fonction de barrière de la peau des personnes atteintes de dermatite atopique.

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.

La couche cornée (stratum corneum, SC), la couche épidermique la plus externe, joue un rôle essentiel dans la fonction de barrière cutanée. Cette revue se penche sur le processus complexe de dégradation des protéines au sein de la couche cornée, ce qui explique les rôles des enzymes spécifiques, les mécanismes de régulation et l'impact qui en résulte sur diverses affections cutanées. La dégradation des protéines est un processus subtil, orchestré par une série d'enzymes protéolytiques telles que les kallikréines. Ces enzymes sont responsables de la décomposition des cornéodesmosomes et de la desquamation ordonnée des cornéocytes, un processus essentiel à l'homéostasie de la peau. Un autre processus enzymatique essentiel est la dégradation des protéines telles que la filaggrine et la génération d'acides aminés et de leurs dérivés, nécessaires aux propriétés physiologiques de traitement de l'eau de la SC. La régulation de ces activités protéolytiques est complexe, impliquant un équilibre entre les inhibiteurs endogènes et d'autres facteurs tels que le pH, l'hydratation et les facteurs de stress environnementaux. Le dérèglement de l'activité de la protéase est lié à un spectre d'affections cutanées, allant de la xérose à des maladies inflammatoires telles que la dermatite atopique et le psoriasis. Une dégradation aberrante des protéines peut compromettre la fonction de barrière cutanée, augmenter la perte d'eau tissulaire et augmenter la sensibilité aux infections et aux allergènes. Comprendre les facteurs affectant la dégradation des protéines peut contribuer au développement de produits de soins de la peau ciblés. Les progrès en biochimie et en dermatologie ont ouvert la voie à la recherche de principes actifs conçus pour moduler l'activité de la protéase. Ces innovations peuvent offrir des pistes thérapeutiques prometteuses pour améliorer la fonction de la barrière cutanée et traiter les troubles cutanés. Cette revue souligne l'importance de la dégradation enzymatique des protéines dans la SC et ses mécanismes de régulation. Elle fournit des informations sur la physiopathologie des maladies cutanées et souligne le potentiel de nouvelles interventions pour soins de la peau. En comblant le fossé entre la recherche fondamentale et les applications pratiques, cet article vise à inspirer des recherches supplémentaires pour mieux comprendre la physiologie de la peau et l'innovation dans le domaine du développement de produits de soins de la peau.

The importance of stratum corneum ω-linoleoyloxyacylceramides in human skin barrier health: their biochemistry, processing enzymes and metabolites involved in corneocyte lipid envelope maturation.

Over the past 50 years there have been great strides made in the discovery of the composition and relevance of the total stratum corneum (SC) ceramide matrix. However, the focus of this review is on the free intercellular class of ω-linoleoyloxyacylceramides, corneocyte-bound ceramides and associated lipids known as the corneocyte lipid envelope (CLE) together with their processing enzymes involved in aiding ceramide attachment the corneocyte protein envelope (CPE). Two structural models and partially shared biosynthetic pathways have been proposed for the attachment of CPE-bound O-ceramides (ω-hydroxyceramides attached to glutamate residues of proteins in the (CPE) using the 12R-lipoxygenase (12R-LOX)/epidermal lipoxygenase-3 (eLOX3)/epoxide hydrolase-3 (EPHX3)/unknown esterase/ transglutaminase-1 (TG1) attachment pathway) and CPE-bound EO-ceramides (epoxy-enone ceramides attached to cysteine residues of proteins in the CPE using the 12R-LOX/eLOX3/short chain dehydrogenase/reductase family 9C member 7 (SDR9C7)/non-enzymatic attachment pathway), i.e. there is a bifurcation step beyond epidermal eLOX3. Their formation and structures will be discussed as well as their relevance in compromised skin barrier conditions together with our own work on SC maturation examined by proteomics, lipidomics, enzyme immunolocalization studies, mechanical fragility assays and Nile red staining of corneocyte envelopes (CE). Reduced levels of 12R-LOX, eLOX3, SDR9C7 and TG1 were observed in photodamaged skin of the cheeks that were associated with reduced SC maturation as evidenced by Nile red staining and increased CE fragility. In the severely photodamaged cheeks of Albino African SC we also observed increased levels of acylceramides. Concomitantly by reducing the activity of 12R-LOX by antibody inhibition and TG1 inhibition with a known chemical inhibitor, we demonstrated in a humidity-based ex vivo SC maturation model that these enzymes contributed to increased CE hydrophobicity and mechanical integrity. We hypothesize that at least the CPE-bound O-ceramide pathway is operational in the SC. Nevertheless, our understanding of the full complexity of ω-linoleoyloxyacylceramides and the composition of the CLE is limited particularly on cosmetically relevant body sites such as the face.

Ces 50 dernières années, de grandes avancées ont eu lieu dans la découverte de la composition de la matrice de céramides de toute la couche cornée et de son importance. Cependant, cette revue se concentre sur la classe intercellulaire libre des ω­linoléoyloxyacylcéramides, les céramides liés aux cornéocytes et les lipides associés appelés « enveloppe lipidique des cornéocytes ¼ (ELC), ainsi que sur leurs enzymes de transformation impliquées dans la fixation des céramides sur l'enveloppe protéique des cornéocytes (EPC). Deux modèles structurels et des voies de biosynthèse partiellement partagées ont été proposés pour la fixation des O­céramides liés à l'EPC (ω­hydroxycéramides fixés aux résidus glutamate des protéines dans l'[EPC] en utilisant la 12R­lipoxygénase [12R­LOX]/la lipoxygénase épidermique 3 [eLOX3]/l'époxyde hydrolase 3 [EPHX3]/une voie de fixation inconnue de l'estérase/de la transglutaminase 1 [TG1]) et les EO­céramides liés à l'EPC (céramides époxy­énone fixés aux résidus de cystéine des protéines de l'EPC utilisant la 12R­LOX/l'eLOX3/la déshydrogénase à chaîne courte/la réductase membre 7 de la famille 9C [SDR9C7]/une voie de fixation non enzymatique). En d'autres termes, il existe une étape de bifurcation au­delà de l'eLOX3 épidermique. Leur formation et leur structure, ainsi que leur importance dans des conditions de barrière cutanée compromises, font ici l'objet d'une discussion. Nous abordons également nos propres travaux sur la maturation de la couche cornée selon la protéomique, la lipidomique, les études d'immunolocalisation enzymatique, les tests de fragilité mécanique et la coloration au rouge du Nil des enveloppes cornées (EC). Des taux réduits de 12R­LOX, d'eLOX3, de SDR9C7 et de TG1, associés à une maturation réduite de la couche cornée, ont été observés sur la peau photo­lésée des joues, comme en témoigne la coloration au rouge du Nil et la fragilité accrue des EC. Nous avons également observé une augmentation des taux d'acylcéramides sur les joues de personnes africaines atteintes d'albinisme dont la couche cornée a été sévèrement photo­lésée. En réduisant l'activité de la 12R­LOX par inhibition des anticorps et du TG1 avec un inhibiteur chimique connu, nous avons pu démontrer, dans un modèle de maturation de la couche cornée ex vivo basé sur l'humidité, que ces enzymes contribuaient à accroître le caractère hydrophobe des EC, ainsi que leur intégrité mécanique. Nous émettons l'hypothèse qu'au moins la voie de l'O­céramide liée à l'EPC fonctionne dans la couche cornée. Néanmoins, notre compréhension de la complexité complète des ω­linoléoyloxyacylcéramides et de la composition de l'ELC reste limitée, en particulier à des parties du corps ou l'esthétique est importante, comme le visage.

Impact of multilamellar formulations on stratum corneum lipid organization and epidermal lipid barrier enhancement (Part II).

INTRODUCTION: The integrity of the stratum corneum (SC) is crucial for the skin's barrier function, protecting against environmental stressors and minimizing transepidermal water loss. Advances in skincare formulations have introduced multilamellar systems designed to emulate the SC's lipid composition and organization. This study hypothesizes that the application of a multilamellar cream will significantly impact the SC's lipid content and lamellar structure, thereby enhancing the epidermal barrier. METHODS: A saturated phosphatidylcholine-based multilamellar cream was applied to a cohort of adult subjects with very dry skin. Electron microscopy was utilized to analyse the micro-morphology of the cream and its integration into the lipid-depleted SC. Lipid analysis was conducted to quantify changes in the intercellular lipid matrix. RESULTS: Transmission-electron microscopy (TEM) imaging demonstrated that the multilamellar cream possesses a structured arrangement comparable to the natural SC architecture. Short-term application revealed a time-dependent restoration of lipid bilayers, while a 14-day regimen showed a marked increase in lipid lamellae density and length within the SC. Lipid analysis indicated a significant increase in total lipid content, with notable enhancements in ceramide and free fatty acid levels, without altering cholesterol levels. Lipid ratio analysis further confirmed the rebalancing of the SC's lipid composition. DISCUSSION: The multilamellar cream selectively increased specific lipids critical for barrier function, suggesting an action mechanism that aligns with the skin's natural regulatory processes. This selective augmentation indicates the potential of the formulation to not only restore but also enhance the epidermal barrier, with the maintenance of physiological lipid ratios suggesting compatibility with intrinsic repair mechanisms. CONCLUSION: The study confirms that a multilamellar cream can significantly improve the SC's lipid composition and structural integrity, indicating enhanced barrier function. They are pivotal for skincare professionals, dermatologists, and product developers, enriching the understanding of multilamellar creams' benefits and applications in improving epidermal barrier function.

INTRODUCTION: l'intégrité de la couche cornée (SC, stratum corneum) est essentielle pour la fonction de barrière cutanée, protégeant contre les facteurs de stress environnementaux et réduisant au minimum la perte d'eau transépidermique. Les progrès en matière de formulations pour soins de la peau ont introduit des systèmes multilamellaires conçus pour simuler la composition et l'organisation lipidique du SC. Cette étude émet l'hypothèse que l'application d'une crème multilamellaire aura un impact significatif sur la teneur en lipides et la structure lamellaire du SC, améliorant ainsi la barrière épidermique. MÉTHODES: Une crème multilamellaire à base de phosphatidylcholine saturée a été appliquée à une cohorte de sujets adultes présentant une peau très sèche. La microscopie électronique a été utilisée pour analyser la micromorphologie de la crème et son intégration dans le SC délipidé. Une analyse lipidique a été réalisée pour quantifier les changements dans la matrice lipidique intercellulaire. RÉSULTATS: l'imagerie par TEM a démontré que la crème multilamellaire possède un agencement structuré comparable à l'architecture naturelle du SC. L'application à court terme a révélé une restauration dépendante du temps des bicouches lipidiques, tandis qu'un schéma posologique de 14 jours a montré une augmentation marquée de la densité et de la longueur des lamelles lipidiques au sein du SC. L'analyse lipidique a indiqué une augmentation significative de la teneur lipidique totale, avec des améliorations notables des taux de céramide et d'acides gras libres, sans altérer les taux de cholestérol. L'analyse du rapport lipidique a confirmé le rééquilibrage de la composition lipidique du SC. DISCUSSION: la crème multilamellaire a augmenté de manière sélective les lipides spécifiques essentiels à la fonction de barrière, suggérant un mécanisme d'action qui s'aligne sur les processus de régulation naturels de la peau. Cette augmentation sélective indique le potentiel de la formulation non seulement à restaurer, mais également à améliorer la barrière épidermique, avec le maintien des rapports lipidiques physiologiques suggérant une compatibilité avec les mécanismes de réparation intrinsèques. CONCLUSION: l'étude confirme qu'une crème multilamellaire peut améliorer de manière significative la composition lipidique et l'intégrité structurelle du SC, ce qui indique une meilleure fonction de barrière. Ils sont essentiels pour les professionnels de la peau, les dermatologues et les développeurs de produits, et enrichissent la compréhension des bénéfices et des applications des crèmes multilamellaires dans l'amélioration de la fonction de la barrière épidermique.

Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment.

Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.

Epidermal and dermal hydration in relation to skin color parameters.

BACKGROUND: Our goal was to investigate linkages between skin color parameters and skin hydration. Since most prior studies focused on stratum corneum hydration, we focused on epidermal and dermal hydration in relation to skin color parameters in both sexes. MATERIALS AND METHODS: Thirty adults (16 female) with an age ± SD of 24.3 ± 0.6 years participated. Three sites on both volar forearms were evaluated for melanin index (MI), erythema index (EI), Individual Typology Angle (ITA), tissue dielectric constant (TDC) values to depths of 0.5 mm (TDC0.5) and 2.5 mm (TDC2.5), and Fitzpatrick skin type (FST). RESULTS: MI and EI were highly correlated (r = 0.800, p < 0.001) with maximum differences in MI and ITA along the arm of 3% and 6.3% with no difference between arms. Male MI was greater than females (p < 0.01). Male TDC2.5 was 36.1 ± 5.4 and correlated with EI (r = 0.231, p = 0.035). Contrastingly, female TDC25 was 28.5 ± 3.6 with no correlation with EI but was correlated with MI (r = -0.301, p = 0.003). These differential patterns held true for TDC0.5. For both sexes, FST and ITA were highly correlated (r = -0.756, p < 0.001). CONCLUSIONS: The findings revealed several correlations between skin color parameters and hydration that differed between males in females in some cases. The observed correlations may indicate that melanin may differentially impact water-holding capacity between sexes and provides a future research target. Further, these initial findings also may hold significance for dermatological assessments and the customization of skincare treatments tailored to individual skin types and demographics.

Spatial distribution of active compounds in stratum corneum-partitioning between corneocytes and lipid matrix.

The interaction of active substances with molecular structures in stratum corneum (SC) is crucial for the efficacy and safety of cosmetic formulations and topical drugs. However, the molecular architecture of SC is highly complex and methods to unambiguously localize exogenous molecules within SC are lacking. Consequently, little is known about the distribution of actives within SC, and proposed penetration mechanisms through SC are typically limited to simple diffusion via a tortuous (lipid only) or transverse (across corneocytes and lipid matrix) pathway. In this work, 3D mass spectrometry imaging is used to determine the spatial distributions of four active substances at subcellular resolution in SC, including partitioning between the corneocytes and the intercellular lipid matrix. The results indicate that caffeine, 2-methyl resorcinol and oxybenzone are homogeneously distributed in the corneocytes but largely absent in the lipid matrix, despite considerable differences in lipophilicity. In contrast, the distribution- of jasmonic acid derivative is more inhomogeneous and indicates considerable localization to both the lipid phase and the corneocytes.

Exploring the epidermal architecture of Dasyprocta prymnolopha: A potential dermatology research model.

The agouti (Dasyprocta prymnolopha) is a medium-sized, wild rodent that is highly rustic and docile. Its size and ease of management make it a viable candidate for an alternative animal model to traditional murine subjects. However, data on the epidermal strata of agoutis are lacking, with significant uncertainties persisting regarding their skin's characterization. This study aimed to describe and quantify the epidermal strata of skin biopsies from male and female agoutis raised in captivity, to further validate the species as a model for dermatological research. Ultrastructural evaluations through atomic force microscopy (AFM) and stereological analyses were conducted, revealing significant differences between the layers of the skin; notably, the dermis exhibited a greater total volume than the epidermis. The findings suggest that the epidermal strata are well-defined, with the volume likely correlating to the size and cellular density of the keratinocytes. Corneodesmosomes and tonofilaments were identified across all epidermal layers, indicating the probable maintenance of anchoring protein activity, even post-cornification of these cells. These results suggest that the agouti may serve as a promising model for dermatological studies, owing to the homogeneity of its cutaneous tissue across different body regions and the distinct volume and morphology of its epithelial stratification, which could enhance the applicability of systematic investigative methods in the future.

Epidermal stem cells: skin surveillance and clinical perspective.

The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.

Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study.

AIMS: To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. METHODS: Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability. RESULTS: The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at -0.00005 established non-inferiority against a margin of -0.4 (p = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9-1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9-0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. INTERPRETATION: Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.

Highly Adhesive and Stretchable Epidermal Electrode for Bimodal Recording Patch.

For numerous biological and human-machine applications, it is critical to have a stable electrophysiological interface to obtain reliable signals. To achieve this, epidermal electrodes should possess conductivity, stretchability, and adhesiveness. However, limited types of materials can simultaneously satisfy these requirements to provide satisfying recording performance. Here, we present a dry electromyography (EMG) electrode based on conductive polymers and tea polyphenol (CPT), which offers adhesiveness (0.51 N/cm), stretchability (157%), and low impedance (14 kΩ cm2 at 100 Hz). The adhesiveness of the electrode is attributed to the interaction between catechol groups and hydroxyls in the polymer blend. This adhesive electrode ensures stable EMG recording even in the presence of vibrations and provides signals with a high signal-to-noise ratio (>25 dB) for over 72 h. By integrating the CPT electrode with a liquid metal strain sensor, we have developed a bimodal rehabilitation monitoring patch (BRMP) for sports injuries. The patch utilizes Kinesio Tape as a substrate, which serves to accelerate rehabilitation. It also tackles the challenge of recording with knee braces by fitting snugly between the brace and the skin, due to its thin and stretchable design. CPT electrodes not only enable BRMP to assist clinicians in formulating effective rehabilitation plans and offer patients a more comfortable rehabilitation experience, but also hold promise for future applications in biological and human-machine interface domains.