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Introduction A burn is a trauma that breaks the skin barrier, causing local and systemic responses. Treatment is complex, multiprofessional and expensive. In addition to surgical treatment, topical dressings can be used to keep the wound moist, reduce the risk of infection and stimulate healing. Clinical studies show that topical use of fibroblast growth factors may accelerate healing. An assessment of the quality of the available evidence and its strength of recommendation is necessary. Objective This study aimed to evaluate the effectiveness and safety of topical use of fibroblast growth factor, compared to other topical treatments or placebo, in the healing of burns, to determine the strength of recommendation. Method Based on a defined search strategy, randomized and quasi-randomized clinical trials, available in electronic databases, were gathered. These compare the topical use of FGF versus other topical or non-treatment. The primary outcome was healing and as adverse effects: pain, infection and mortality. The systematic review protocol was registered on the PROSPERO platform (CRD42018089556), developed in accordance with the “Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015” and within the “SWiM guideline 2019”. GRADEpro was used for the critical analysis of the methodology of the studies. Results Four clinical trials were found, in which FGF reduced the healing time and improved the appearance of the scar. Two trials were determined to be of low strength, while two others have a moderate recommendation strength. Conclusion This review gathered available evidence, between low and moderate recommendation strength for the use of FGF as a topical dressing. Further rigorous trials are needed to improve the strength of recommendation for topical use of FGF for burns.

Cycloastragenol (CA) is a plant saponin that functions as a telomerase activator, and it has been made as an oral anti-aging supplement and use as active ingredient in topical cosmetic products. The anti-aging performance in cosmetic products have only been evaluated by description of skin appearance, while direct topical penetration of CA across the skin barrier still needs to be confirmed. The objective of this work was to design encapsulation vehicles to deliver CA across the skin barrier using commercially available ingredients through scalable processes, and to prove its topical penetration. Phospholipid vesicles including liposomes, ethosomes, and transethosomes were prepared using soy and sunflower phospholipids and different penetration enhancers, including ethanol and surfactants. The loading capacity of CA was analyzed using high performance liquid chromatography, and the topical penetration of CA was evaluated using Franz diffusion cells with pig skin. Transethosomes using Tween 80, Span 40, or dicetylphosphate as the penetration enhancer showed better CA delivery across the skin barrier than ethosomes or emulsifier α-gels. Results of this work provide evidence that CA encapsulated in phospholipid vesicles can be transported across the skin barrier. These encapsulation systems could be used for the design of CA-containing anti-aging cosmetic products.

Purpose High prevalence, unreliable risk discrimination and poor clinical outcomes are observed in malignant and benign breast diseases (BD). The involvement of microbial communities in the development of BD has become topical, and distal influences of microbial dysregulation in the breast have been well established. Despite advances, the role of the breast skin microbiota in BD remains unclear. Interactions between the skin microbiota and the underlying mucosal immune system are complex. In homeostasis, the skin offers a physical barrier protecting underlying breast tissue from skin commensals and noxious environmental triggers. Our review aims to illuminate the role of the skin microbiota in the development of BD. Methods Adhering to the PRISMA protocol, a systematic review was conducted utilising the Medline and Embase search engines. Results Through a comprehensive search of the last ten years, twenty-two studies satisfied the inclusion criteria. Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were identified as the most prevalent phyla of both breast tissue and skin in healthy controls and BD. High abundance of skin commensals, specifically some species of Staphylococcus, have been linked in breast cancer and metastases. Similarly, dysregulated microbial abundance is also seen in inflammatory and implant-associated BD. These findings raise the hypothesis that the skin microbiota plays a role in tissue homeostasis and may contribute to a range of breast pathologies. Several mechanisms of microbial transfer to underlying tissue have been proposed, including retrograde transfer through ductal systems, breakdown of the skin barrier, and migration through nipple-aspirate fluid. Conclusion Our review provides preliminary insights into the skin microbiota as a modifiable risk factor for BD. This raises opportunities for future studies in antimicrobials/probiotics as an adjunct to, or replacement of surgery; a diagnostic and/or prognostic tool for BD; and the possibility of conditioning the microbiota to manage BD., Highlights • The breast skin microbiota as a modifiable risk factor in breast disease. • The utilisation of antimicrobial or probiotic treatments in breast disease. • The role of the breast skin microbiota as a diagnostic or prognostic tool in breast disease.

Objective To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD). Methods Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group, model group, whole formula group (WF), exterior-releasing formula group (ERF), interior-clearing formula group (ICF), and positive control group (PC). A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and pH, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin, and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction. Results Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly. Conclusions Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Objective Evidence supports the relationship between the skin barrier and allergic conditions. This narrative review evaluates what role the cutaneous barrier may play in the pathogenesis, disease course, and management of allergic rhinitis (AR). Data Sources A literature review of the MEDLINE (PubMed), Embase, Cochrane, and SCOPUS Sciverse databases was conducted to identify available evidence. Reference lists of pertinent papers were searched using a snowball technique. Study Selections Papers published in English from all years until December 2020 were included. Papers that did not address the relationship between AR and the skin and hypothesis papers were excluded. Results The cutaneous barrier shares histologic characteristics with the sinonasal epithelial barrier, which may explain commonalities between AR and atopic dermatitis. A disruption in the epithelial barrier could be a common pathway in the development of multiple allergic conditions. The skin is a common target for the treatment of AR. Available data that look at the relationship between the skin and AR often include other topics such as other atopic disorders and the role of the epithelial barrier. Increased understanding of how the cutaneous barrier affects AR may lead to new innovations in its management. Conclusion The connection between the cutaneous barrier and AR holds possibilities for further investigation, and these may lead to a better understanding and future innovations for all atopic diseases.

The skin barrier is critical in ensuring homeostasis, yet factors influencing its development, repair, and maintenance are ill-defined. In this issue of Cell Host & Microbe, Uberoi et al. demonstrate the skin microbiota's role in maintaining barrier integrity via AHR signaling in keratinocytes, which has implications for skin disease management.

Background This study seeks to establish the skin barrier dysfunction model at the heel via tape-stripping (TS) by evaluating the skin moisturizing effects. Materials and methods Nineteen young, female participated in the study. A sequence of TS was performed at the heel and trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, and surface pH were measured. Following TS, the subjects were divided into three groups: moisturizer, emollient, and overcoat. These agents were applied daily at night, and the skin parameters were measured the next morning for a week. Results The TEWL value of TS immediately and 5 min after TS were significantly higher than what was obtained before TS, while the SC hydration after TS was significantly lower than what was obtained before TS. However, there were no significant differences in the skin parameters among the three agents on day 7 after application, with the two-way ANOVA showing no interaction among the agents and number of days. Conclusion The skin barrier dysfunction model at the heel was established by TS in healthy, young adults. However, the physiological function of the skin at the heel did not change drastically and showed no differences even after continuous application for 7 days.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies.

Skin and soft tissue infections are common in diabetics. Diabetic foot infection usually results from disruption of the skin barrier, trauma, pressure, or ischemic wounds. These wounds may become secondarily infected or lead to development of adjacent soft tissue or deeper bone infection. Clinical assessment and diagnosis of these conditions using a multidisciplinary management approach, including careful attention to antibiotic selection, lead to the best outcomes in patient care.

Transdermal drug delivery is an attractive route for dermatological disease therapy because it can directly target the lesion site on the skin, reduce adverse reactions associated with systemic administration, and improve patient compliance. However, the stratum corneum, as the main skin barrier, severely limits transdermal drug penetration, with compromised bioavailability. Microneedles (MNs), which are leveraged to markedly improve the penetration of therapeutic agents by piercing the stratum corneum and creating hundreds of reversible microchannels in a minimally invasive manner, have been envisioned as a milestone for effective transdermal drug delivery, especially for superficial disease therapy. Here, the emergence of versatile MNs for the transdermal delivery of various drugs is reviewed, particularly focusing on the application of MNs for the treatment of diverse skin diseases, including superficial tumors, scars, psoriasis, herpes, acne, and alopecia. Additionally, the promises and challenges of the widespread translation of MN-mediated transdermal drug delivery in the dermatology field are summarized.

Background Chronic pruritus dramatically disrupts quality of life, impairs sleep, and is difficult to treat. The pathogenesis and severity of chronic itch can vary significantly with race. Black skin has inherent structural and molecular characteristics that exacerbates pruritus, leading to unique presentations of pruritic conditions and added challenges in finding effective therapies. The aim of this review is to discuss structural variances in black skin, the subsequent epidemiological disparities in chronic pruritic conditions, and clinical management pearls for the management of itch in black patients. Methods Current literature including mechanistic, translational, and epidemiological data on racial differences in pruritus focusing on black skin were reviewed in Pubmed. Findings Black skin has several unique structural properties related to the pathogenesis of pruritus, including increased trans-epidermal water loss, decreased ceramide levels, lower pH in the stratum corneum, and increased size of mast cells. Black patients consequently are disproportionately affected by chronic pruritic disorders including atopic dermatitis, prurigo nodularis, HIV-related pruritic dermatoses, and cutaneous T-cell lymphoma. Conclusion Pruritus and chronic pruritus disorders disproportionately affects black patients. Management of pruritus of special importance in black patients includes low pH skin care products to protect the skin barrier along with emollients to diminish trans-epidermal water loss. Further mechanistic studies are needed to characterize racial differences in biomarkers and therapeutic targets of chronic itch.

Background The non-invasive skin barrier measurements transepidermal water loss, stratum corneum hydration and the skin surface pH are widely used in clinical skin research. Relative and absolute measurement errors of these measurements are unknown in geriatric care settings. Material and methods Transepidermal water loss, stratum corneum hydration, skin surface pH and temperature were measured on the volar forearm and lower leg twice by trained raters within a cross-sectional study in ten nursing homes. Intrarater reliability was calculated using the ICC (1,1). Intrarater agreement was analyzed using Bland Altman Plots with limits of agreement. Results Two hundred twenty-three residents were included and mean age was 84.2 years. The highest ICC was found for transepidermal water loss and skin surface temperature of the leg with 0.95 (95% CI 0.93 to 0.96). The ICC of the stratum corneum was 0.91 (95% CI 0.88 to 0.93) for both investigated skin areas. The measurement of the pH at the lower leg had the lowest ICC with 0.73 (95% CI 0.66 to 0.78). Highest limits of agreement of approximately 8 a.u. were calculated for stratum corneum hydration and lowest limits of agreement of approximately 1 °C were calculated for skin surface pH. Conclusion Relative measurement errors of transepidermal water loss and stratum corneum hydration were very low indicating that single measurements provide reliable estimates in this population and setting. However, the absolute measurement errors were high for both of these parameters. To increase reliability of skin surface pH we recommend at least two repeated measurements.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

The relationship between infant skin health and food allergy pathogenesis is the focus of intense research activity, on the basis that interventions to improve infant skin health may potentially lead to the prevention of food allergy. Current evidence does not provide conclusive findings on the mechanisms of food allergy development but does support the possibility that food allergy develops through transcutaneous sensitisation to allergenic peptides. In this article, we review the evidence for this model of food allergy development, assess strategies currently being tested for prevention of food allergy through cutaneous interventions, and identify key knowledge gaps which might be explored in future work. Keywords: Atopic dermatitis, Food allergy, Infant, Prevention, Skin barrier

Objective To provide an overview of filaggrin biology and the role of filaggrin variants in atopic dermatitis (AD) and allergic disease. Data Sources We performed a PubMed literature review consisting mainly of studies relating to filaggrin in the last 5 years. Study Selections We selected articles that were found in PubMed using the search terms filaggrin, atopic dermatitis, skin barrier, and atopy. Results Filaggrin plays an important role in the development of AD and allergic disease. Novel methods in measuring filaggrin expression and identifying filaggrin mutations aid in stratifying this patient cohort. We review new insights into understanding the role of filaggrin in AD and allergic disease. Conclusion Filaggrin remains a very important player in the pathogenesis of atopic dermatitis and allergic disease. This review looks at recent studies that aid our understanding of this crucial epidermal protein.

Background Peripheral intravenous catheters (PIVCs) break the skin barrier, and preinsertion antiseptic disinfection and sterile dressings are used to reduce risk of catheter-related bloodstream infection (CRBSI). In this study, the impact of PIVC skin site colonization on tip colonization and the development of CRBSI was investigated. Methods A total of 137 patients’ PIVC skin site swabs and paired PIVC tips were collected at catheter removal, cultured, and bacterial species and clonality were identified. Results Of 137 patients, 45 (33%) had colonized skin sites and/or PIVC tips. Of 16 patients with paired colonization of both the skin site and PIVC tips, 11 (69%) were colonized with the same bacterial species. Of these, 77% were clonally related, including 1 identical clone of Pseudomonas aeruginosa in a patient with systemic infection and the same organism identified in blood culture. Conclusions The results demonstrate that opportunistic pathogen colonization at the skin site poses a significant risk for PIVC colonization and CRBSI. Further research is needed to improve current preinsertion antiseptic disinfection of PIVC skin site and the sterile insertion procedure to potentially reduce PIVC colonization and infection risk.

Transdermal naloxone delivery could be a potential option for treating opioid-induced pruritus, but naloxone does not permeate skin well because of its hydrophilic nature. Microneedles (MNs) could overcome the skin barrier by painlessly creating microchannels in the skin to permit naloxone absorption to therapeutic levels. This study investigated how ionization correlates with naloxone permeation across MN-treated skin. Hydrogels containing 0.2, 0.5, or 1% naloxone were formulated with 1% cross-linked polyacrylic acid (polymer) and adjusted to pH 5, 6.5, or 7.4. Porcine skin was treated with MNs and naloxone gel, and in vitro permeation studies were performed using an in-line diffusion setup. Gel structural properties were evaluated using rheology. All gels had viscoelastic properties and good spreadability. Naloxone permeation through intact skin was highest from pH 7.4 gels when naloxone is unionized, in contrast with undetectable concentrations permeated from pH 5 gels with 100% ionization. Combining MN treatment with pH 5 gels significantly enhanced permeation and resulted in steady-state flux that would achieve therapeutic delivery. Absorption lag time was affected by MN length and naloxone gel concentration. Polymer concentration did not influence drug permeability. This study demonstrates that transdermal naloxone delivery with MNs is a viable treatment option for opioid-induced pruritus.

Red color is pervasive in local and systemic skin conditions. It is a color that often reflects variations of dermal blood flow and extends beyond the rubor and calor of inflammation. The pathophysiology of red skin involves remote and local chemical mediators that dilate arteriolar smooth muscle and increase blood flow to superficial vessels and capillary beds. Incident light hits hemoglobin, which preferentially absorbs light of shorter wavelengths, such as blue, and reflects warmer colors. Due to its pervasiveness and consistency, red color is a useful descriptive factor in helping narrow a differential diagnosis. Red skin disorders include a variety of conditions involving endocrine mediators, cardiovascular responses, and the disruption of the skin barrier. An understanding of the blood's role in these disorders equips clinicians to generate differential diagnoses through the lens of pathophysiology. Dermatologists can improve management by considering red skin as part of systemic disease rather than as an isolated incident.

Dysbiosis is a key pathogenic factor in the cycle of skin barrier impairment and inflammation in atopic dermatitis (AD). Skin microbial composition in AD is characterized by increased presence of Staphylococcus aureus (S. aureus) and decrease in microbial diversity and commensal bacterial species. Attenuation of S. aureus-driven inflammation aids in breaking the itch-scratch cycle via modulation of the cutaneous immune response. Skin bacterial transplant (SBT), a form of bacteriotherapy, is an intriguing treatment modality for restoration of a healthy skin microbiome in AD patients. Studies on the effects of topically-applied bacterial products, probiotics and SBT have yielded promising results in animal models and human studies of AD. This review discusses the rationale and evidence for SBT in AD and outlines future investigative directions for the clinical application of microbiome restoration in dermatology.

The skin barrier is mainly present in the stratum corneum (SC), composed of corneocytes surrounded by intercellular lipid lamellae, and attached by corneodesmosome. The tight junction attached to the lateral walls of keratinocytes in the upper part of the stratum granulosum is also included in the skin barrier. During aging, the following structures and functions of the skin barrier are changed or disturbed: (1) skin barrier structure, (2) permeability barrier function, (3) epidermal calcium gradient, (4) epidermal lipid synthesis and SC lipid processing, (5) cytokine production and response after insults, (6) SC acidity, (7) SC hydration, and (8) antimicrobial barrier. Patients with diabetes also show changes in the skin barrier similar to those in aged skin, and the characteristics of the skin barrier are very similar. Understanding the pathogenic mechanisms of the skin barrier in aging will permit us to develop therapeutic strategies for aged or diabetic skin.

Skin barrier keeps the “inside-in” and the “outside-out” forming a protective blanket against external insults. Epidermal lipids such as ceramides, fatty acids, triglycerides and cholesterol are integral components in driving the formation and maintenance of epidermal permeability barrier (EPB). A breach in this lipid barrier sets the platform for the subsequent onset and progression of atopic dermatitis (AD). Such lipids are also important in the normal functioning of different organisms, both plants and animals and in diseases including cancer. A double increase in AD rate in the recent years and the chronic nature of this disorder emphasizes the need of this review to shed light on the multifaceted role of the diverse types of lipids in mediating AD pathogenesis.

Cellulitis and erysipelas are local soft tissue infections that occur following the entry of bacteria through a disrupted skin barrier. These infections are relatively common and early diagnosis is essential to treatment success. As dermatologists, we need to be familiar with the clinical presentation, diagnosis, and treatment of these infections. In this article, we provide a review of the literature and update on clinical manifestations, predisposing factors, microbiology, diagnosis, treatment, and complications. We also review the current situation in Chile.

Ceramides are essential lipids for skin permeability barrier function, and a wide variety of ceramide species exist in the stratum corneum (SC). Although ceramides with long-chain bases (LCBs) of various lengths have been identified in the human SC, a quantitative analysis that distinguishes ceramide species with different LCB chain lengths has not been yet published. Therefore, the whole picture of human SC ceramides remains unclear. Here, we conducted LC/MS/MS analyses to detect individual ceramide species differing in both the LCB and FA chain lengths and quantified 1,327 unbound ceramides and 254 protein-bound ceramides: the largest number of ceramide species reported to date. Ceramides containing an LCB whose chain length was C16-26 were present in the human SC. Of these, C18 (28.6%) was the most abundant, followed by C20 (24.8%) and C22 (12.8%). Each ceramide class had a characteristic distribution of LCB chain lengths and was divided into five groups according to this distribution. There was almost no difference in FA composition between the ceramide species containing LCBs of different chain lengths. Furthermore, we demonstrated that one of the serine palmitoyltransferase (SPT) complexes, SPTLC1/SPTLC3/SPTSSB, was able to produce C16-24 LCBs. The expression levels of all subunits constituting the SPT complexes increased during keratinocyte differentiation, resulting in the observed chain-length diversity of LCBs in the human SC. This study provides a molecular basis for elucidating human SC ceramide diversity and the pathogenesis of skin disorders.

To investigate effect of Yupingfeng granules, prepared with Chinese Medicines, on the wound healing and on the expression of aquaporin 3 (AQP3) and the skin barrier in the animal models of atopic dermatitis (AD).Acute skin lesions of AD models were prepared using 2,4-dinitrochlorobenzo (DNCB) in mice and animals were treated with either Yupingfeng granules or placebo for two weeks. Skin wound healing outcome was assessed by measuring skin thickness, weight (quality) of the skin, and trans-epidermal water loss (TEWL). Expression of AQP3 mRNA and protein was assessed by reverse transcriotion polymerase chain reaction (RT-PCR) and immunoblotting, respectively.Yupingfeng granule treatment resulted in significant acceleration of wound healing with 63.64% efficiency, which was significantly higher than that of placebo granule treatment (31.82%, P0.01 by Wilcoxon Rank-sum test). Skin thickness, weight of the wounded skin, and TEWL were significantly higher in the AD models compared to that of normal animals. Treatment with Yupingfeng granules resulted in significant decrease in skin thickness [(937 ± 31) vs (360 ± 21) urn, P0.01], weight of the wounded skin [(42 ± 4) vs (24 ± 5) mg, P0.01], and TEWL [(30 ± 4) vs (13 ± 4) g•h-1•m-2, P0.01]. Yupingfeng granules also significantly down-regulated mRNA and protein expression of AQP3 in the animal models.Our findings suggested that Yupingfeng granules could be used in AD treatment.

The skin barrier function of the female vulva is weak and often stimulated by various external factors, and this area is susceptible to chronic eczema. Currently, the primary treatment for local chronic eczema is topical corticosteroids. However, long-term corticosteroid treatment can further damage the skin barrier, resulting in bacterial or viral infections that complicate the condition. Once chronic eczema is associated with viral warts, medication choices are limited. In this case report, a patient with a ten-year history of chronic vulvar eczema became infected with human papillomavirus and eventually developed multiple warts. After three sessions of photodynamic therapy, all warts subsided, and her skin lichenification and pruritis improved.

Long-periodicity phase (LPP) lamellar structures in intercellular lipid matrixes of the stratum corneum (SC) are considered important for maintenance of skin permeability barriers. Acylceramides are essential components of LPP structures, and their absence influences skin barriers under physiological and pathological conditions, such as atopic dermatitis and dry skin. Although topical applications of acylceramide have been shown to facilitate maintenance of the skin barrier, it is unknown whether topically applied acylceramides are incorporated into intercellular lipids to form LPP structures. Thus, we assessed the effects of topical treatments with monomodal acylceramides on the formation of LPP structures in a surfactant-insulted reconstructed human epidermis model using small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses. In SAXS experiments, LPP structures give rise to a diffraction peak which indicates the presence of a structure with a 13 nm real space repeat distance. LPP patterns of intercellular lipid matrixes in the SC were disrupted’ by surfactant treatments and were recovered by topical acylceramide treatments. TEM images also showed specific repeating patterns of LPP structures, indicating that topical acylceramide treatments facilitate recovery of LPP structures in the SC. The present data show that the application of acylceramides might temporarily modify the lipid structure to resemble that of normal skin although the underlying cause of dry or diseased skin is not fully clarified.

Pruritus is a common symptom in cutaneous T-cell lymphoma (CTCL) and critically affects the quality of life of patients. Understanding the pruritogenesis has led to development of new therapeutic agents with promising outcomes in management of this recalcitrant symptom. Clinical assessments are warranted to aid in evaluation of treatment response or disease recurrence. Severe pruritus scores may require further investigation of emotional distress for a better patient approach. Dermatologists play a key role in the treatment of CTCL-pruritus by guiding the patient in the importance of preserving the integrity of the skin barrier.

Skin barrier disruption plays a role in the pathogenesis of atopic dermatitis (AD) in humans. However, little is known about skin barrier (dys-) function in Canine Atopic Dermatitis. The properties of lipids located in the outermost layer of the skin, the stratum corneum (SC) are considered to be important for the barrier. In the present study the lipid composition and lipid organization of the SC of AD dogs and control dogs were examined. The lipid composition of lesional AD skin as compared to control skin, showed a reduced free fatty acid level and a decreased ratio of ceramide[NS] C44/C34, in which C44 and C34 are the total numbers of carbon atoms of the sphingosine (S) and non-hydroxy (N) acyl chains. As a consequence of the observed changes in lipid composition in AD lesional skin the lamellar organization of lipids altered and a shift from orthorhombic to hexagonal lipid packing was monitored. Simultaneously an increased conformational disordering occurred. These changes are expected to compromise the integrity of the skin barrier. The C44/C34 chain length ratio of ceramide[NS] also showed a decreasing nonlinear relationship with the AD severity score (CADESI). Taken together, canine atopic skin showed alterations in SC lipid properties, similar to the changes observed in atopic dermatitis in humans, that correlated with a disruption of the skin barrier. Hence lipids play an important role in the pathogenesis of Canine Atopic Dermatitis.

According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D-printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas., Graphical Abstract

Approaches to develop three-dimensional (3-D) vascularized human skin equivalents (vHSEs) that can mimic native skin are currently gaining momentum. Yet, the reproducible fabrication of vHSEs with superior barrier properties, sustained vasculature and high durability remains a challenge. Here, we aim to improve the stability of scaffold-free vHSEs by utilizing a dynamic flow culture system. We established that in static vHSEs, the uncontrolled interplay between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), and unconstrained angiogenesis lead to dermal instability. To obviate, we explored the effect of dynamic flow environment on vHSEs durability, using a custom-built 3-D printed bioreactor. Dynamic flow culture restored tissue homeostasis by balancing the expression of MMPs and their inhibitors, and via modulation of angiogenesis. This consecutively improved the skin barrier properties, facilitated the fabrication of thicker tissues, and enhanced wound closure. Moreover, we show that vHSEs in flow culture promoted vascular openings as perfusable sites. Altogether, this study highlights the importance of a dynamic milieu in the regulation of cellular signaling for the cultivation of vascularized tissue constructs.

Intercellular lipids in the stratum corneum (SC), such as ceramide (CER), free fatty acid (FFA), and cholesterol (CHOL), contribute to the formation of stable lamellar structures in the SC, making them important for skin barrier function. β-Galactosylceramide (GalCer) is a glycosphingolipid that is used in some cosmetics and quasi-drugs in anticipation of a moisturizing effect. GalCer promotes keratinocyte differentiation and increases CER production by increasing β-glucocerebrosidase (β-GCase) activity. However, few reports have described the mechanism of these effects, and detailed studies on the role of GalCer in intercellular lipid production in the SC have not been conducted. This study investigated the effect of GalCer on the metabolism and production of intercellular lipids in the SC in a three-dimensional cultured epidermis model. After reacting GalCer with a homogenate solution of three-dimensional cultured epidermis, GalCer was hardly metabolized. Treatment of the three-dimensional cultured epidermis with GalCer increased the expression of genes involved in the β-GCase metabolic pathway and promoted CER production. In addition, GalCer treatment reduced the expression of FFA metabolism-related genes as well as palmitic acid levels. In addition, transepidermal water loss, which is a barrier index, was reduced by GalCer treatment. These findings suggested that GalCer, which is hardly metabolized, affects the production of intercellular lipids in the SC and improves skin barrier function., Article 101135

The skin barrier prevents moisture evaporation and the entry of foreign substances such as allergens. Ceramides are one of the most important factors for maintaining skin barrier function. Melia toosendan is a plant of the Meliaceae family, and its fruit extracts have been used in Traditional Chinese Medicine as analgesics and anthelmintics; however, its ability to increase ceramide levels has not been reported. In this study, we screened for compounds present in M. toosendan fruit extracts that increase ceramide levels in the skin. We fractionated the extracts based on their activity to identify the active components. Nimbolinins, limonoids such as toosendanin, and hydroxylated unsaturated fatty acids were found to be the major active components. The structure-activity relationship of toosendanin derivatives indicated that the sites around R4 and R5 contributed to the activity. To the best of our knowledge, this is the first report showing that limonoids promote ceramide production in skin cells. Therefore, M. toosendan fruit extracts may be used to develop products for improving the skin barrier function.

Acne is a chronic disease that may cause sequels such as atrophic or hypertrophic scars or post-inflammatory hyperpigmentation. Topical and systemic medications with proven pharmacologic activity and which have received marketing authorization are the key actors in the treatment of acne. However, these topical or systemic treatments frequently cause adverse effects related to impairment of the skin barrier, and cosmetics must therefore be used in combination to help protect the skin barrier. Nowadays, new cosmetic products containing active ingredients tested in vitro or in a small number of subjects have changed the world of cosmetics. In being described as "dermo-cosmetic" and in integrating active ingredients in their formulations, these cosmetics are now being presented as being specifically adapted for a given disease, and no longer limited to skin care and hygiene but suitable as an adjunctive or even an alternative to current medications. The aim of this article is to provide a better understanding of the respective roles of medications and cosmetics in the management of acne.

Stratum corneum is the primary skin barrier to percutaneous absorption. Since 1980, topical liposomal formulations have been proposed and successfully employed for increasing the drug penetration through the skin. There is no clear consensus on the drug penetration mechanism from topically applied liposomes, despite a vast amount of research. One of the reasons for the ambiguity is that the interactions between the stratum corneum and liposomes are in nanoscale, which makes them difficult to probe. In this study, we employed tip-enhanced Raman scattering (TERS) to gain a better understanding of the interactions between the human stratum corneum and topically applied liposomal system called invasomes. TERS is capable of imaging at nanometer spatial resolution and can provide structural information at the nanometer scale. A sample preparation technique was developed and calibrated to enable TERS on complex stratum corneum samples. Invasomes prepared from a head deuterated phospholipid were employed to aid identification of topically applied liposomal phospholipid in the stratum corneum. Results presented in this study give for the first time a strong spectroscopic evidence along with high-resolution images to show intact invasome vesicles deep in the stratum corneum upon topical application.

Linoleate triol esters are intermediates along the pathway of formation of the mammalian skin permeability barrier. In connection with the study of their involvement in barrier formation we required access to isomerically pure and defined samples of four linoleate triol esters. A common synthetic strategy was developed starting from isomeric alkynols derived from d-tartaric acid and 2-deoxy-d-ribose.

BACKGROUND Cardiovascular implantable electronic devices (CIED) infection is associated with significant morbidity and devastating sequelae for the patients. The use of incremental perioperative antibiotics, as well as use of an antibiotic impregnated pouch to reduce periprocedural device infections have recently been investigated. Trials investigating these additive interventions have shown only modest benefit, in addition these interventions carry a high cost to the system. Cost of antibiotic pouches can be greater than $1000 per use and use of additive antibiotics in all comers was shown to be neutral in Canadian centers. We sought to determine the effect of skin barrier use at reducing the risk of CIED infection as a simple, low cost intervention at time of device implantation. METHODS AND RESULTS We conducted an audit of all CIED implant procedures completed between Jan 2007 and April 2020 by 17 experienced operators in a shared procedure practice model. All device infections requiring reoperation or extraction were collected prospectively and diagnosis reconfirmed by an infectious disease specialist. A skin barrier was used as per physician preference and operations were retrospectively evaluated for use of skin barrier. Antibiotic use and periprocedural care were consistent in all procedures as per institutional protocol. Over a 13-year period 14,607 procedures were completed (mean age 72 +/- 14 years, female 35%). A total of 7816 pacemakers, 3292 ICDs, 1482 CRTs, and 1635 device upgrade or lead revision procedures were performed. 3913 procedures were completed with skin barrier and 10693 without. There were 90 infections in the no barrier group vs. 19 infections in the barrier group (0.84% vs. 0.48%, p=0.02). After a sensitivity analysis adjusting for the number of procedures, procedure type (ILR, PPM, ICD, CRT, de novo vs. upgrade vs. revision vs. generator replacement), the difference remained statistically significant. CONCLUSION Our data suggests that skin barrier use may be protective against infection. Considering low cost of skin barrier and catastrophic sequelae of device infection, the use of skin barrier during the procedure may be considered as an additional preventative measure to reduce device related infection. The low rates of infection in the barrier group are likely due to operator experience, use of standardized guideline directed perioperative care, and likely reduction of skin flora translocation during the procedure. Re-evaluation after transition to use of skin barrier for all cases will help further confirm these findings.

Psoriasis is a gene and immune-mediated inflammatory skin disease without any improvement and its treatment is completely dependent on symptom control. Presently, it is affecting millions of people worldwide. Hypodermic needles, topical creams, along with transdermal patches have been more frequently used for transdermal administration of medications. Because of the skin layer, Stratum corneum which gives protection towards the drug and/or foreign particles and only some molecules are allowed to access the target, so the effectiveness of most of the transdermal delivery systems is reduced. A modern method of a delivery system termed as ‘microneedles’ enhances the transport of the medication directly into the skin by bypassing the skin barrier layer solve different problems concerning the conventional transdermal delivery systems. The purpose of this review is to explore about MNs used as a transdermal drug delivery system for treating psoriasis. Owing to the range of benefits offered, such as minimal harm, painlessness, comfort, and increased patient compliance, the MNs approach is considered to be far safer in comparison to conventional transdermal delivery systems. The word MNs have inclined much attention by researchers in recent times and the MNs technology is transiently growing. MNs are categorized by scholars into four main types: dissolving microneedles (DMNs), coated microneedles (CMNs), solid microneedles (SMNs), and hollow microneedles (HMNs). As per their exceptional features like shape and usage, each type of MNs possesses distinct advantages. By reviewing the literature, characteristics and geometry of MNs, mechanism of MNs, and commonly used drugs for the microneedle's fabrication were considered. The polymers and methods used for preparing MNs and applications of microneedle technology with prime focus on psoriasis therapy are explained. Evaluation parameters of MNs such as characteristics, dimensional, mechanical, in vitro, and in vivo evaluations, along with the patents filed and marketed products of MNs are reviewed and included in this article. This piece of writing is therefore intended to include a written description of the advancements of the use of MNs in effective psoriasis treatment.

To advance drug development representative reliable skin models are indispensable. Animal skin as test model for human skin delivery is restricted as their properties greatly differ from human skin. In vitro 3D-human skin equivalents (HSEs) are valuable tools as they recapitulate important aspects of the human skin. However, HSEs still lack the full barrier functionality as observed in native human skin, resulting in suboptimal screening outcome. In this review we provide an overview of established in-house and commercially available HSEs and discuss in more detail to what extent their skin barrier biology is mimicked in vitro focusing on the lipid properties and cornified envelope. Further, we will illustrate how underlying factors, such as culture medium improvements and environmental factors affect the barrier lipids. Lastly, potential improvements in skin barrier function will be proposed aiming at a new generation of HSEs that may replace animal skin delivery studies fully.