Dermal-epidermal Junction Research Articles

Novel Thermus thermophilus and Bacillus subtilis mixed-culture ferment extract provides potent skin benefits invitro and protects skin from aging.

Skin aging is one of the most abundant aging-related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency. In the present study, we aim to fully demonstrate the skin-related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed-culture ferment (TBFE). TBFE was prepared through an innovative mixed-culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both invitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms. Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin-3, and dermal-epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro-inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those invitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti-aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening. In summary, we demonstrate that a novel mixed-culture ferment extract has promising anti-aging effects, which may be attributed to anti-oxidation, anti-inflammation, and promotion of autophagy in skin cells.

Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.

Anti-IL-17 monoclonal antibodies and bullous pemphigoid: treatment or causal agents? A case series and review of the literature.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (TH1)/TH17-dominant cytokine milieu, typical of patients with psoriasis, to a TH2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

Integration of transcriptomics and spatial biology analyses reveals Galactomyces ferment filtrate promotes epidermal interconnectivity via induction of keratinocyte differentiation, proliferation and cellular bioenergetics.

Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress. We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in exvivo skin explant tissue. The effect of GFF on cell adhesion rates, cellular ATP levels and proliferation rates were quantitated. Oxidative phosphorylation and glycolytic rates were measured under normal and stress-induced conditions. Transcriptomics from keratinocytes and exvivo skin explants from multiple donors show GFF induces keratinocyte differentiation, skin barrier development and cell adhesion while simultaneously repressing cellular stress and inflammatory related processes. Spatial transcriptomics profiling of exvivo skin indicated basal keratinocytes at the epidermal-dermal junction and cornifying keratinocytes in the top layer of the epidermis as the primary cell types influenced by GFF treatment. Additionally, GFF significantly increases crosstalk between suprabasal and basal keratinocytes. To support these findings, we show that GFF can significantly increase cell adhesion and proliferation in keratinocytes. GFF also protected overall cellular bioenergetics under metabolic or oxidative stress conditions. Our findings provide novel insights into cellular differences and epidermal spatial localization in response to GFF, supporting previous findings that this filtrate has a significant impact on epidermal biology and homeostasis, particularly on spatially defined crosstalk. We propose that GFF can help maintain epidermal health by enhancing keratinocyte crosstalk and differentiation/proliferation balance as well as promoting an enhanced response to stress.

A randomised, controlled, multicentre trial of imiquimod versus radiotherapy for lentigo maligna.

9502 Background: Lentigo maligna (LM) is a form of melanoma in situ that occurs mainly on sun exposed skin. For patients with LM who are not suitable for surgery due to location, size, patient preference or co-morbidities, topical imiquimod or radiotherapy are alternative non-surgical treatments. There are no prospective randomized controlled trial data to form the basis of any recommendations for the management of LM. This multi-institutional, international randomized phase 3 trial evaluated the efficacy and safety of imiquimod verus radiotherapy for patients with LM. The primary hypothesis was that treatment of LM with topical imiquimod would result in fewer treatment failures than radiotherapy. Methods: Patients aged > 18 years old with LM not suitable for surgery were randomly assigned (1:1) to imiquimod or radiotherapy. The primary endpoint was treatment failure within 24 months. Secondary endpoints included development of invasive disease within the area, side effects and patient-reported quality of life (QOL) assessed with validated questionnaires (skin-specific Skindex-16 and generic EQ-5D-5L). Results: Between August 2015 and November 2021, 126 patients were randomised from 8 centres (imiquimod 60, radiotherapy 58 in final analysis). The median age was 72 years and 94.9% of lesions were on the head and neck area. Median follow-up was 27 months (range 3-62 months). Six (10.5%) patients in the imiquimod group and 12 (24.0%) patients in the radiotherapy group developed recurrence within 24 months (OR 2.68, 95% CI, 0·92-7.8, p = 0.063). Median time to recurrence was not reached in either group. Treatment failure was significantly different within the subgroup of patients who had reflectance confocal microscopy (RCM) follow up of the LM (imiquimod 4/46, 8.7% radiotherapy 13/52 25.0%; OR 3.50 95% CI 1.05-11.65, p = 0.033). Only one RCM feature was associated with failure at 24 months and significantly different between treatment groups : the presence of atypical round cells at the dermal-epidermal junction (6.9 % of imiquimod failure and 27% of radiotherapy failure: p = 0.035). There were no differences between trial groups in patient-reported skin symptoms (itching, burning/stinging, pain, irritation), skin-specific emotional and functional QOL impacts, or generic QOL at any time points. Conclusions: Both imiquimod and radiotherapy are valid, well-tolerated and efficient non-surgical options for LM. There is no significant difference in the acute or long term QoL for the two treatments. Clinical trial information: NCT02394132 .

Presentation of Meibomian Acini Compared to Dermal Papillae of the Eyelid Margin, Using Confocal Laser Scanning Microscopy and Corresponding Histology.

Numerous studies have investigated the eyelid margin using confocal laser scanning microscopy (CLSM) and have presented morphological alterations of the examined structures, which were presumed to be Meibomian acini. However, recent data confirm that these structures are the cross-sections of dermal papillae of the dermoepidermal junction. This study aims to present the morphological appearance of Meibomian acini examined by confocal laser scanning microscopy in comparison to dermal papillae, and to reveal the corresponding patterns with specific histological sections. Twenty healthy patients were examined with a CLSM device in vivo at the marginal edge of the eyelid. Twenty-two samples of full-thickness eyelid wedges from 22 patients treated surgically with ectropion were collected, of which 11 freshly excised samples were imaged on the incision surface with CLSM ex vivo and 11 eyelids underwent conventional histological preparation. The represented structures on CLSM images were compared to Meibomian acini on histological sections in terms of area, longest and shortest diameter, as well as depth and density. On in vivo CLSM images, Meibomian orifices, epidermal cells, and dermal connective tissue could be identified, the latter in a cross-sectional view of the dermal papillae surrounded by basal cells of the epidermis, forming reflective ring-like structures. All morphological parameters of these structures differed from Meibomian acini measured on histological sections. In contrast, the CLSM images of the incision surface showed acinar units with the same morphology as the Meibomian acini seen in the histological images and no statistically significant difference was found between the corresponding parameters. The morphological appearance of Meibomian acini differs from the structures that were previously presumed as Meibomian glands on CLSM images. In vivo imaging of Meibomian glands by commonly used in vivo CLSM cannot be performed.

P01 Remodelling of the dermoepidermal junction occurs in intrinsically aged Far East Asian skin without significant epidermal atrophy

Abstract Introduction and aims Ageing is characterized by a gradual decline in physiological function and is influenced by both intrinsic genetic and extrinsic lifestyle and environmental factors. However, much of our knowledge of cutaneous ageing comes from the study of White populations. We have previously shown that the organization of young healthy skin is ethnicity-dependent and that altered epidermal morphology in White volunteers correlates with loss of biomechanical function in the skin. In this study, we used epidermal morphometry to determine whether parameters associated with intrinsic skin ageing in White skin are also observed in Far East Asian skin. Methods Archival skin samples were obtained from the Asian Skin Biobank [young (3–21 years), N = 38, 37 male samples (Chinese, n = 16; Malay, n = 16; other Far East, n = 6); aged (61–86 years), N = 7, one male sample (Chinese, n = 6; Malay, n = 1)] and stained with haematoxylin and eosin prior to image analysis for dermoepidermal junction (DEJ) convolution and measurement of epidermal thickness. Weigert’s resorcin-fuchsin stain was used to ensure samples were photoprotected. Results Weigert’s resorcin-fuchsin stain revealed that all samples were photoprotected, with no evidence of solar elastosis. We next compared whether geographic ancestry of our local Far East Asian population impacted epidermal morphology in young skin; neither DEJ convolution nor epidermal thickness were impacted by geographic ancestry. However, a significant flattening of the DEJ was observed between young and aged samples (P < 0.01). Interestingly, no significant difference in epidermal thickness was observed as a function of age. Conclusions While intrinsically aged Asian skin undergoes the same flattening of the DEJ that is seen in White populations, epidermal thickness does not significantly alter; this is in stark contrast to intrinsically aged White skin, where epidermal atrophy is observed. Hence, the trajectory of intrinsic cutaneous ageing may be ethnicity-dependent, providing further evidence that studies of skin from different ethnicities are necessary.

Revisiting the Effect of Aging on the Transport of Molecules through the Skin.

Both intrinsic and extrinsic aging lead to a series of morphological changes in the skin including the flattening of the dermal-epidermal junction, increased stratum corneum dryness, reduction in sebaceous gland activity and enzyme activity as well as atrophy of blood vessels. In this study, the impact of these changes on the transport of molecules through the skin was revised. The increase in the number of transdermal formulations on the market in recent decades and life expectancy represent the main reasons for an in-depth discussion of this topic. Furthermore, elderly subjects have often been excluded from clinical trials due to polypharmacy, raising concerns in terms of efficacy and safety. In this way, ex vivo and in vivo studies comparing the transport of molecules through the mature and young skin were analyzed in detail. The reduced water content in mature skin had a significant impact on the transport rate of hydrophilic molecules. The lower enzymatic activity in aged skin, in turn, would explain changes in the activation of prodrugs. Interestingly, greater deposition of nanoparticles was also found in mature skin. In vivo models should be prioritized in future experimental studies as they allow to evaluate both absorption and metabolism simultaneously, providing more realistic information.

Criteria for melanocytic lesions in LC-OCT.

Line-field confocal optical coherence tomography (LC-OCT) is an emerging diagnostic tool with imaging depth reaching ~400 μm and a novel three-dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. Our aim was to establish the diagnostic criteria for melanocytic lesions using LC-OCT and identify the most significant architectural and cytologic features associated with malignancy. A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC-OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well-defined DEJ and wave pattern (vertical). A series of diagnostic criteria for the identification of melanocytic lesions with LC-OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility.

Radiofrequency Treatment Attenuates Age-Related Changes in Dermal-Epidermal Junctions of Animal Skin.

The dermal-epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-β production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-β, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-β and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-β. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. To determine the potential of retinoids to repair photoaged black skin. An exploratory intervention study was performed using an invivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

Application of dermoscopy and reflectance confocal microscopy in vivo in the evaluation of nevi in children.

Melanocytic nevi are frequently observed in the pediatric population. While newly acquired nevi can appear during childhood, congenital nevi can continue to grow and clinically change, making patient caregivers concerned. Reflectance confocal microscopy (RCM) in vivo is a noninvasive tool that might enhance the diagnostic accuracy of dermoscopy, reducing the rate of unnecessary surgical procedures. This study aimed to assess the utility of RCM in increasing the diagnostic accuracy of pediatric melanocytic nevi that show pigmentation changes or grow rapidly. Pediatric patients who presented between January 2022 and February 2023 in a single institution with rapidly growing melanocytic nevi or nevi that presented changes in the pigmentation were included in the study. All nevi were evaluated by means of dermoscopy and RCM. Forty-two patients with a total of 42 melanocytic nevi were included. Most lesions showed a honeycombed pattern (n = 21, 50%). On RCM, only 3 of 42 nevi presented atypical cells within the epidermis (7.1%). Evaluation of the dermoepidermal junction (DEJ) revealed the predominance of the meshwork pattern (n = 22, 52.4%). Notably, features considered significant for atypical melanocytic nevi included 9 nevi with scant atypical melanocytes (21.4%) and 3 nevi with nonedge papillae (7.1%). None of the studied lesions required biopsy among this cohort. Most rapidly growing and clinically changing nevi rarely exhibit single atypical cells in the DEJ. The RCM served as a valuable adjunct to dermoscopy, allowing reassurance in the evaluation of these lesions.

A Novel Method for Fabricating the Undulating Structures at Dermal-Epidermal Junction by Composite Molding Process.

The dermal-epidermal junction (DEJ), located between the dermal-epidermal layers in human skin tissue, plays a significant role in its function. However, the limitations of biomaterial properties and microstructure fabrication methods mean that most current tissue engineered skin models do not consider the existence of DEJ. In this study, a nanofiber membrane that simulates the fluctuating structure of skin DEJ was prepared by the composite molding process. Electrospinning is a technique for the production of nanofibers, which can customize the physical and biological properties of biomaterials. At present, electrospinning technology is widely used in the simulation of customized natural skin DEJ. In this study, four different concentration ratios of poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanofiber membranes were prepared based on electrospinning technology. We selected a 15%PLGA + 5%PCL nanofiber membrane with mechanical properties, dimensional stability, hydrophilicity, and biocompatibility after physical properties and biological characterization. Then, the array-based microstructure model was prepared by three-dimensional (3D) printing. Subsequently, the microstructure was created on a 15%PLGA + 5%PCL membrane by the micro-imprinting process. Finally, the cell proliferation and live/dead tests of keratinocytes (HaCaTs) and fibroblasts (HSFs) were measured on the microstructural membrane and flat membrane. The results showed that 15%PLGA + 5%PCL microstructure membrane was more beneficial to promote the adhesion and proliferation of HaCaTs and HSFs than a flat membrane.

Tirbanibulin 1% Ointment Effectiveness for Actinic Keratosis Treatment Evaluated by Dynamic Optical Coherence Tomography

Background. Actinic keratosis (AK) is a common premalignant skin condition. Its diagnosis is based on a clinical and sometimes dermoscopic examination, but, in some situations, a skin biopsy may be necessary. Dynamic optical coherence tomography (D-OCT) can often bypass this need, by noninvasive evaluation of skin morphology. Early and effective treatment of AKs is important to prevent the progression to invasive squamous cell carcinoma (iSCC). Tirbanibulin 1% ointment, a new topical field therapy for AKs, has recently been introduced. Objectives. The aim of this study was to evaluate the efficacy and safety of tirbanibulin 1% ointment for the field treatment of nonhyperkeratotic, nonhypertrophic AKs (Olsen grade 1) on the face and/or scalp in adults, using D-OCT technology. Methods. Patients, presenting multiple, mild to moderate AKs on the face and scalp, in treatment with tirbanibulin 1% ointment for five consecutive days of an area measuring 25 cm2, were evaluated with videodermoscopy (V-track Vidix 4.0) and D-OCT (VivoSight Dx, Michelson Diagnostics Ltd., Kent, England, United Kingdom), as normal clinical practice. The lesions were staged according to the Olsen classification, excluding the most aggressive lesions. Results. We retrospectively evaluated 50 patients (27 males and 23 females, mean age 76 ± 7.9 years). At 57 days posttreatment, the complete clearance rate was 68% (n = 34) and partial clearance rate was 76% (n = 38). D-OCT showed markedly improved morphology, including a better recognizable dermal-epidermal junction (DEJ), associated with reduced inflammation. The most common adverse events reported were erythema and scaling, which were mostly mild and self-limiting. Conclusions. This study demonstrated that tirbanibulin may be considered an effective and well-tolerated treatment option for nonhyperkeratotic, nonhypertrophic AKs. It showed a favorable safety profile, with mostly mild adverse events. D-OCT can be considered a useful tool for personalizing AK treatment and monitoring.

Morphometric analysis of the effects of high molecular weight sodium hyaluronate and amino acids mixture on face rejuvenation.

Skin aging can be observed at various levels in the epidermis, dermis, and dermo-epidermal junction. Reducing the cosmetic effects of skin aging in the facial region is a widespread demand due to common aesthetic concerns. Consequently, many injectable products on the market promise antiaging effects and cosmetic improvements. We aimed to evaluate the cosmetic efficacy of a high molecular weight sodium hyaluronate and amino acids mixture for the facial region using morphometric analysis. This study evaluates the morphometric effectiveness of an injectable mixture (high molecular weight sodium hyaluronate, glycine, L-Proline, L-leucine, L-lysine HCL, L-valine, and L-alanine collagen active ingredient) on the mid-face and jawline in women aged 30-55. We used morphological measurements and digital image data to assess changes and determine effectiveness. Various computational methods were applied simultaneously with statistical tests for validation. The hydration assessment showed a significant increase on both sides of the face. A noticeable decrease was observed in gonion angle, bitragion breadth, bigonion breadth, and marionette wrinkle scale. These results suggest combining mechanical and chemical stimulation from the injection and its components (hyaluronic and amino acids) effectively enhances skin quality. The study indicates that the mechanical stimulation of the injection improves skin quality. Combining hyaluronic and amino acids (collagen, elastin, and pro-synthetic) is a safe and effective alternative for antiaging treatments.

Epidermolysis Bullosa: Two rare case reports of COL7A1 and EBS-GEN SEV KRT14 variants with review of literature

EpidermolysisBullosa is a rare hereditary skin condition that causes blisters. Genes encoding structural proteins at or near the dermal-epidermal junction are mutated recessively or dominantly, and this is the primary cause of EB. Herein, two Chinese boys were diagnosed with the condition, each with a different variant in a gene that serves as a reference for EB genetic counseling. Skincare significantly impacted their prognosis and quality of life.Case presentationTwo Chinese boys, with phenotypically normal parents, have been diagnosed with distinct blister symptoms, one with Dominant Dystrophic Epidermolysis Bullosa and the other with a severe form of Epidermolysis Bullosa Simplex. The first patient had a G-to-A variant in the COL7A1 allele, at nucleotide position 6163 which was named “G2055A”. The proband is heterozygous for Dystrophic Epidermolysis Bullosa due to a COL7A1 allele with a glycine substitution at the triple helix domain. A similar variant has been discovered in his mother, indicating its potential transmission to future generations. Another patient had severe Epidermolysis Bullosa Simplex with a rare c.377T > A variant resulting in substitution of amino acid p.Leu126Arg (NM_000526.5 (c.377T > G, p.Leu126Arg) in the Keratin 14 gene. In prior literature, Keratin 14 has been associated with an excellent prognosis. However, our patient with this infrequent variant tragically died from sepsis at 21 days old. There has been a reported occurrence of the variant only once.ConclusionOur study reveals that Epidermolysis Bullosa patients with COL7A1 c.6163G > A and KRT14 c.377T>A variants have different clinical presentations, with dominant forms of Dystrophic EB having milder phenotypes than recessive ones. Thus, the better prognosis in the c.6163G > A patient. Furthermore, c.377T>A patient was more prone to infection than the patient with c.6163G>A gene variant. Genetic testing is crucial for identifying the specific variant responsible and improving treatment options.

Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma insitu (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

The pathological function of neutrophils in pemphigoid diseases

Abstract Pemphigoid diseases (PDs) are a group of autoimmune blistering diseases, including bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid, linear immunoglobulin A disease, and other rare variants. These diseases are characterized by the presence of autoantibodies that target proteins at the dermal-epidermal junction, resulting in the formation of tense blisters and erosions on the skin and/or mucosa. The current therapeutic approaches, such as systemic corticosteroid, are associated with significant adverse effects, highlighting that safer and more effective treatment options are an urgent clinical need. To address this unmet need, a comprehensive understanding of the detailed mechanisms underlying PDs is essential. Based on their histopathological infiltration in pemphigoid lesions, neutrophils have long been implicated as major contributors to the initiation and progression of the diseases. Numerous in vivo and in vitro studies have investigated the role of neutrophils in the pemphigoid pathology, revealing various pathological mechanisms induced by these cells, including the release of neutrophil elastase and matrix metalloproteinase-9, as well as the formation of neutrophil extracellular traps. The present review provides a comprehensive summary and critical evaluation of the current understanding regarding the role of neutrophils in PDs. In addition, it discusses the potential of targeting neutrophil-associated pathways as a novel therapeutic approach for the diseases.

Risk assessment of pressure injuries in newborns. Appropriateness of Glamorgan and NSRAS scales: a scoping review

The newborn's skin must undergo a transition process as a result of the passage from an aqueous to an aerobic environment. This process occurs over a period of approximately 2 to 8 weeks. The skin of newborns has important anatomical and physiological differences compared to those of older children and adults. It is thin, with fewer appendages; the stratum corneum is not present; the dermal-epidermal junction is reduced; intercellular junctions are weaker; the secretions of the sebaceous glands are limited and the pH is generally neutral. All these factors make the newborn's skin more fragile to any stimulus. To have effective prevention and intervention procedures, an accurate and practical risk assessment tool should be identified as a preliminary step for adequate prevention. Unfortunately, only few validated tools are available to assess the risk of PUs in children, especially newborns. The objective of the study is to examine the adherence of the most used tools for the assessment of PU risk in newborns, in particular to make a comparison of the limits and advantages of the most frequently used tools in neonatal settings, the Glamorgan scale and NSRAS. To respond to the main objective, a scoping review of the literature was conducted. 54 studies were identified. Further analysis was conducted, which led to the exclusion of articles that did not examine the characteristics of newborn skin, the risk factors related to PUs and the appropriateness of the NSRAS and Glamorgan tools, for a final selection of 35 studies. Patients admitted to NICU represent the paediatric category most exposed to the risk of developing pressure ulcers. Factors such as reduced mobility, together with the pressure exerted by aids or devices, increase the risk of pressure injuries. The risk factors that most expose the newborn to risk are the structure of the skin and medical devices. Nurses should implement preventative measures to control the risk of PU. The use of specific tools is necessary to detect the risk of PUs in newborns and implement preventive measures. PUs risk assessment is one of the nursing care strategies for prevention. Therefore, operators need a valid, reliable, and predictive scale. Lastly, we recommend the use of NSRAS for future research and for the education of healthcare professionals in the neonatal area.