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Examination revealed multiple, symmetrical, discrete, skin-coloured, dome-shaped waxy papules 2-4 mm in size over her face, trunk and extremities with lesions concentrating over the periorbital area and upper trunk (Figure 1). Graph: Figure 1 Index patient showing multiple skin-coloured waxy papules 2-4 mm in size on her forehead and periorbital area. A woman in her 50s, presented for evaluation of progressive asymptomatic papules of 2 years duration. [Extracted from the article]

Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications. [ABSTRACT FROM AUTHOR]

This study demonstrates, for the first time, the proof-of-concept of a novel immunosensor, a touchpad-based immunochromatographic strip, that non-invasively extracts and detects skin surface proteins. The strip was composed of a nitrocellulose membrane at the center, where a spot of anti-human IgG capture antibody was physically adsorbed. The capture antibody spot was covered with a glass fiber membrane impregnated with phosphate-buffered saline (PBS) to extract skin surface proteins, avoiding direct contact of the human skin with the capture antibodies. Skin surface IgG was detected in two steps: (1) touching the capture antibody via a glass fiber membrane containing PBS, and (2) dipping the strip into the Au-nanoparticle-labeled secondary antibody to visualize the existence of the captured skin surface IgG on the strip. We qualitatively demonstrated that using a very small amount of PBS while maintaining contact with the skin, skin surface proteins can be concentrated and detected, even with a relatively low-sensitivity immunochromatographic chip. This sensor is expected to be a potential biosensor for the non-invasive diagnosis of the integrity of human skin. [Display omitted] • The proof-of-concept of a novel touchpad-based immunochromatographic strip was demonstrated for the first time. • This strip enabled the detection of the skin surface IgG in only two steps. • A very small amount of PBS-based extraction solution concentrated the extracted IgG to a visually detectable level. [ABSTRACT FROM AUTHOR]

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica , known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-β-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management. [Display omitted] • Reynoutria japonica extract (RJE) ameliorates Dermatophagoides farinae extract (DfE)-induced atopic dermatitis (AD) in NC/Nga mice. • RJE maintains the level of skin barrier proteins on DfE-treated NC/Nga mice. • Emodin-8-β-D-glucoside, a major component of RJE, could contribute to reduce DfE-induced skin inflammation by inhibiting JAK/STAT signaling. • RJE may have potential as therapeutic treatment for skin inflammatory diseases. [ABSTRACT FROM AUTHOR]

(1) Background: Pemphigus is a blistering autoimmune disease of the skin and/or mucous membranes, characterised by the presence of specific autoantibodies directed against structural proteins of the human skin. Recent reports indicate that new haematological parameters, termed Extended Inflammation Parameters (EIP), can be used to assess the activation of immune cells during active inflammation. These include parameters assessing both neutrophil activation (NEUT-RI, NEUT-GI) and the number of activated lymphocytes (RE-LYMP). The aim of this study was to investigate the relationship between changes in NEUT-RI, NEUT-GI and RE-LYMP and the disease activity in patients with pemphigus. (2) Results: The study involved 32 patients with diagnosed different types of pemphigus. Neutrophil activation parameters (NEUT-RI and NEUT-GI) and lymphocytes (RE-LYMP) were significantly higher in these patients compared to the parameters in healthy participants (respectively p = 0.0127, p = 0.0011 and p = 0.0033). The increased quantity of activated lymphocytes (RE-LYMP) also correlated significantly with the extent of skin and/or mucosal lesions in patients assessed by the PDAI scale (p < 0.02). (3) Conclusions: The NEUT-RI, NEUT-GI and RE-LYMP parameters proved to be appropriate markers of inflammation severity in pemphigus, also in relation to local lesions, which was not possible with the inflammation markers (CRP, ESR) used so far on a routine basis. [ABSTRACT FROM AUTHOR]

Psoriasis and skin tumors (such as basal cell carcinoma, squamous cell carcinoma, and melanoma) are chronic diseases that endanger physical and mental health, and yet the causes are largely unknown and treatment options limited. The development of targeted drugs requires a better understanding of the exact pathogenesis of these diseases, and Yes-associated protein (YAP), a member of the Hippo signaling pathway, is believed to play an important role. Psoriasis and skin tumors are characterized by excessive cell proliferation, abnormal differentiation, vasodilation, and proliferation. Here, we review the literature related to YAP-associated disease mechanisms and discuss the latest research. YAP regulates cell apoptosis, proliferation, and differentiation; inhibits cell density and intercellular contacts and angiogenesis; and maintains the three-dimensional structure of the skin. These mechanisms may be associated with the occurrence and development of psoriasis and skin tumors. The results of recent studies have shown that YAP expression is increased in psoriasis and skin tumors. High expression of YAP in psoriasis and skin tumors may indicate its positive functions in skin inflammation and malignancies and may play an important role in disease pathogenesis. The study of new drugs targeting YAP can provide novel approaches for the treatment of skin diseases. [ABSTRACT FROM AUTHOR]

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug–excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed Cmax ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, Tmax was 8 h to 10 h, and t1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis. [ABSTRACT FROM AUTHOR]

In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the stratum corneum, which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections. [ABSTRACT FROM AUTHOR]

The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory and pruritic disease; it can be treated by inhibiting inflammation. Sarcodia suiae sp. is an edible, artificially cultivable red algae with multiple bioactivities. We assessed the anti-inflammatory activity of the ethyl acetate fraction of S. suiae sp. ethanol extract (PD1) on 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions. Results show that PD1 alleviated symptoms and significantly decreased clinical dermatitis score. PD1 inhibited serum immunoglobulin E expression and alleviated swelling in the spleen and subiliac lymph nodes. In skin tissues, PD1 alleviated aberrant hyperplasia, decreased epidermal thickness, and decreased the accumulation of mast cells. PD1 mediated the recovery of skin barrier-related proteins, such as claudin-1 and filaggrin. Our study demonstrated that PD1 has anti-inflammatory effects, alleviates AD symptoms, inhibits inlfammatory responses in skin tissues, and restores barrier function in DNCB-induced AD mice. These findings reveal that S. suiae sp. extract provides an alternative protective option against AD. [ABSTRACT FROM AUTHOR]

Background: The cytokine profile of atopic dermatitis (AD) depends on age, ethnicity, and disease severity. This study examined biomarkers in children with AD collected by tape strips and skin biopsies, and examined whether the levels differed with filaggrin genotype, disease severity, and food allergy. Methods: Twenty‐five children aged 2–14 years with AD were clinically examined. Skin biopsies were collected from lesional skin and tape strips were collected from lesional and non‐lesional skin. We analyzed natural moisturizing factor (NMF) and 17 immune markers represented by mRNA levels in skin biopsies and protein levels in tape strips. Common filaggrin gene mutations were examined in all children. Results: The cytokine profile in lesional skin was dominated by a T helper (Th) 2 response in skin biopsies, and by a general increase in innate inflammation markers (interleukin (IL)‐1α, IL‐1β, IL‐8, IL‐18) along with TARC and CTACK in tape strips. The levels of TARC, CTACK, IL‐8, IL‐18 showed significant correlation with AD severity in both lesional and non‐lesional tape stripped skin, while no significant correlations were observed in skin biopsy data. In tape strips from lesional and non‐lesional skin, the levels of NMF and selected cytokines differed significantly between children with and without FLG mutations and food allergy. Conclusion: Sampling of the stratum corneum with non‐invasive tape strips can be used to identify biomarkers that are associated with disease severity, food allergy and FLG mutations. Skin biopsies showed robust Th2 signature but was inferior for association analysis regarding severity. [ABSTRACT FROM AUTHOR]

Introduction: pemphigus vulgaris (PV) is an autoimmune condition characterized by the loss of adhesion between the epithelial cells and blister formation. The production of autoantibodies against desmosomal proteins, namely, desmoglein (DSG) 1 and DSG3, is considered a main event of PV. A full understanding of the role of adhesion molecules in the pathogenesis of PV is not fully elucidated yet. This study aimed to evaluate and correlate the immunohistochemical expression of Ecadherin (E-cad), DSG1, and DSG3 proteins in oral and skin PV. Methods: this study was a retrospective analysis study. Positive PV cases were stained with anti-E-cad, anti-DSG1, and anti-DSG3 antibodies. The expression of each marker was determined by two pathologists according to an established scoring system: (E-cad: negative, weak, moderate, and strong), (DSG1: negative, weak, and strong), and (DSG3: negative and positive). The Chisquare and Pearson's correlation tests were used to statistically analyze the data. Results: forty-three biopsies (26 skin and 17 oral tissue samples) from 22 males and 21 female PV patients were included. The median age was 40.50 years. In total, the immunohistochemical expression was negative for DSG3, E-cad, and DSG1 in 81.4%, 18.5%, and 16.4%, respectively. DSG1 expression was significantly higher in males than females. A statistically significant correlation was found between E-cad and DSG3 expressions. Conclusion: a significant difference in the expression of markers of both oral and skin PV was absent. Downregulation of DSG3 expression was the hallmark feature that also showed a positive correlation with E-cad expression. [ABSTRACT FROM AUTHOR]

Background: Primary localized cutaneous amyloidosis (PLCA) is defined by the deposition of amyloid protein in the skin without systemic involvement. There are four subtypes of PLCA: lichen amyloidosis (LA), macular amyloidosis (MA), biphasic amyloidosis (BA), and nodular amyloidosis (NA). PLCA occurs most frequently in Latin Americans and Asians. Treatment is not standardized. Objectives: To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA. Materials and Methods: Data of PLCA patients were extracted from the electronic hospital database and included if diagnosis of PLCA was histopathologically confirmed and if sufficient information regarding treatment and follow-up was available. The evaluation of the treatment efficacy was based on a novel score to assess the reduction of itch and skin lesions. Results: In this retrospective, monocentric study, 37 cases of PLCA diagnosed between 2000 and 2020 were included (21 females) with a mean age of 52 years. LA was the most frequent subtype found in 21 patients (56.8%), followed by MA in 10 patients (28%) and BA in 6 patients (16.2%). No cases of NA were included. 22 patients (59.4%) had skin phototype II or III. Regarding treatment, a combination of UVA1 phototherapy with high-potency topical corticosteroids seemed to show the highest efficacy with complete clearance of symptoms in 4 patients (10.8%). A substantial improvement of symptoms was found in 5 patients (12.7%) treated with high-potency topical corticosteroids alone or in combination either with UVA1 or bath PUVA or monotherapy with UVA1 phototherapy or capsaicin (0.075%) cream. Low-/medium-potency topical corticosteroids alone or in combination with UVBnb (311 nm) phototherapy showed a lower efficacy. Conclusion: Our data show that PCLA is a rare disease in central Europe but can also be expected in a predominantly Caucasian population. The best treatment response was achieved with a combination of UVA1 phototherapy and high-potency topical corticosteroids. [ABSTRACT FROM AUTHOR]

IgT is a specific Ig isotype in teleosts, which plays extremely important roles in the mucosal immunity of fish. In the present study, the membrane-bound and secretory IgT of the half-smooth tongue sole (Cynoglossus semilaevis) were identified for the first time. The V-D-J-C structure of two forms of csIgT are translated by the same Cτ gene, and the secretory tail and transmembrane domain were encoded through alternative splicing at the 3′ end of the Cτ4. The CH regions of csIgT had high similarity with that of other flatfish (P. olivaceus and S. maximus). In healthy C. semilaevis , sIgT and mIgT were mainly expressed in mucus related tissues such as skin, intestine and gill. The transcript levels of sIgT and mIgT mRNA showed a significant induction in the immune-related tissues upon Vibrio Harveyi infection. A polyclonal rabbit anti-csIgT was successfully prepared using the csIgT heavy chain recombinant protein. Using this antibody, we detected the native IgT with the molecular mass at 220 kDa in skin total protein under non-reducing SDS-PAGE condition. Immunofluorescence analysis indicated that IgT+ B lymphocytes were intensively located in the skin, gill, intestine, and head kidney of C. semilaevis. These results suggest that IgT may participate in the immune response of C. semilaevis , which will facilitate the investigations of the immunoglobulins of marine fish. • The m IgT and sIgT genes of C. semilaevis were identified for the first time. • sIgT and mIgT were predominantly expressed in the mucosal related tissues. • After V. harveyi infection, the transcript levels of sIgT and mIgT mRNA were up-regulated. • Immunofluorescence showed the IgT+ B cells in skin, intestine, gill and head kidney. [ABSTRACT FROM AUTHOR]

Arnica tincture is a traditional herbal medicine used to treat blunt injuries, e.g., bruises and squeezes. In addition, a potential new use in the treatment of cutaneous leishmaniasis is currently under investigation. Therefore, detailed information about the dermal absorption of the tincture and especially its bioactive constituents, sesquiterpene lactones (STLs) of the helenalin- and 11α,13-dihydrohelenalin type, is mandatory. Consequently, this article reports on dermal absorption studies of Arnica tincture using diffusion cells and porcine skin as well as two human skin samples with different permeability. The amounts of STLs on the skin surfaces, in skin extracts and in the receptor fluids were quantified by ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS). It was found that Arnica STLs permeated into the receptor fluid already 4 h after the application, but the amount was rather low. Within 48 h, a maximum of 8.4%, 14.6% and 36.4% of STLs permeated through porcine skin, human skin A (trans-epidermal water loss (TEWL) = 11.518 g·m−2·h−1) and the more permeable human skin B (TEWL = 17.271 g·m−2·h−1), respectively. The majority of STLs was absorbed (penetrated into the skin; 97.6%, 97.8% and 99.3%) after 48 h but a huge portion could not be extracted from skin and is expected to be irreversibly bound to skin proteins. To better visualize the analytes in different skin layers, a fluorescence-labeled STL, helenalin 3,4-dimethoxycinnamate, was synthesized. Fluorescence microscopic images depict an accumulation of the fluorescent derivative in the epidermis. For the treatment of local, cutaneous complaints, an enrichment of the bioactive substances in the skin may be considered beneficial. [ABSTRACT FROM AUTHOR]

Psoriasis is a common immunologic chronic skin disease that affects at least 100 million individuals worldwide. Adiponectin is associated with psoriasis and suppresses psoriasiform inflammation. Recently, a small-sized transdermally deliverable 5-mer peptide (GLYYF; P5) was discovered as a potential adiponectin receptor 1 agonist. To confirm reduction in adiponectin protein level in the human skin and investigate whether functional adiponectin replenishment by topical P5 application improves psoriasiform skin inflammation. Adiponectin protein expression in the skin of individuals with psoriasis and normal skin was examined by immunofluorescence staining. Imiquimod-induced psoriasis-like skin inflammation was induced in wild-type (WT) and adiponectin-deficient (Adipoq −/−) mice. Vehicle and P5 were topically applied to the back skin and ears of mice. Histological study, reverse-transcription quantitative polymerase chain reaction, multiplex-bead array assay, and flow cytometric analysis were performed. Adiponectin protein expression was downregulated both in the epidermis and dermis of psoriatic lesions as compared to that in the normal skin. Topically applied P5 attenuated the severity of imiquimod-induced psoriatic dermatitis in both WT and Adipoq −/− mice by decreasing the expression of psoriasis-related cytokines (Il17a, Il1b, Il6 , and Tnfa). P5 application significantly reduced the proportion of interleukin-17A–producing γδT cells. Transdermally deliverable adiponectin receptor 1 agonist, P5, can be a potential peptide drug to manage psoriasis by mediating the anti-psoriatic effect of adiponectin • Adiponectin protein expression was lower in psoriasis lesion than in the normal skin. • Topical application a transdermally deliverable AdipoR1 agonist 5-mer peptide, P5, improved psoriasiform dermatitis. • Similar to the native adiponectin, P5 induced an anti-inflammatory effect by reducing IL-17A production from γδT cells. • This study shows that the replenishment of adiponectin function by P5 can be a new anti-psoriatic treatment strategy. [ABSTRACT FROM AUTHOR]

Proteins are ubiquitous macromolecules that display a vast repertoire of chemical and enzymatic functions, making them suitable candidates for chemosignals, used in intraspecific communication. Proteins are present in the skin gland secretions of vertebrates but their identity, and especially, their functions, remain largely unknown. Many lizard species possess femoral glands, i.e., epidermal organs primarily involved in the production and secretion of chemosignals, playing a pivotal role in mate choice and intrasexual communication. The lipophilic fraction of femoral glands has been well studied in lizards. In contrast, proteins have been the focus of only a handful of investigations. Here, we identify and describe inter-individual expression patterns and the functionality of proteins present in femoral glands of male sand lizards (Lacerta agilis) by applying mass spectrometry-based proteomics. Our results show that the total number of proteins varied substantially among individuals. None of the identified femoral gland proteins could be directly linked to chemical communication in lizards, although this result hinges on protein annotation in databases in which squamate semiochemicals are poorly represented. In contrast to our expectations, the proteins consistently expressed across individuals were related to the immune system, antioxidant activity and lipid metabolism as their main functions, showing that proteins in reptilian epidermal glands may have other functions besides chemical communication. Interestingly, we found expression of the Major Histocompatibility Complex (MHC) among the multiple and diverse biological processes enriched in FGs, tentatively supporting a previous hypothesis that MHC was coopted for semiochemical function in sand lizards, specifically in mate recognition. Our study shows that mass spectrometry-based proteomics are a powerful tool for characterizing and deciphering the role of proteins secreted by skin glands in non-model vertebrates. [ABSTRACT FROM AUTHOR]

This study attempted to develop and evaluate controlled-release matrix-type transdermal patches with different ratios of hydrophilic polymers (sodium carboxymethylcellulose and hydroxypropyl methylcellulose) for the local delivery of methotrexate. Transdermal patches were formulated by employing a solvent casting technique using blends of sodium carboxymethylcellulose (CMC-Na) and hydroxypropylmethylcellulose (HPMC) polymers as rate-controlling agents. The F1 formulated patch served as the control formulation with a 1:1 polymer concentration. The F9 formulation served as our optimized formulation due to suitable physicochemical properties yielded through the combination of CMC-Na and HPMC (5:1). Drug excipient compatibilities (ATR-FTIR) were performed as a preformulation study. The ATR-FTIR study depicted great compatibility between the drug and the polymers. Physicochemical parameters, kinetic modeling, in vitro drug release, ex vivo drug permeation, skin drug retention, and in vivo studies were also carried out for the formulated patches. The formulated patches exhibited a clear, smooth, elastic nature with good weight uniformity, % moisture uptake, drug content, and thickness. Physicochemical characterization revealed folding endurance ranging from 62 ± 2.21 to 78 ± 1.54, tensile strength from 9.42 ± 0.52 to 12.32 ± 0.72, % swelling index from 37.16 ± 0.17 to 76.24 ± 1.37, and % drug content from 93.57 ± 5.34 to 98.19 ± 1.56. An increase in the concentration of the CMC-Na polymer (F9) resulted in increased drug release from the formulated transdermal patches. Similarly, drug permeation and retention were found to be higher in the F9 formulation compared to the other formulations (F1–F8). A drug retention analysis revealed that the F9 formulation exhibited 13.43% drug retention in the deep layers of the skin compared to other formulations (F1–F8). The stability study indicated that, during the study period of 60 days, no significant changes in the drug content and physical characteristics were found. ATR-FTIR analysis of rabbit skin samples treated with the formulated transdermal patches revealed that hydrophilic polymers mainly affect the skin proteins (ceramide and keratins). A pharmacokinetic profile revealed Cmax was 1.77.38 ng/mL, Tmax was 12 h, and t1/2 was 17.3 ± 2.21. In vivo studies showed that the skin drug retention of F9 was higher compared to the drug solution. These findings reinforce that methotrexate-based patches can possibly be used for the management of psoriasis. This study can reasonably conclude that methotrexate transdermal matrix-type patches with CMC-Na and HPMC polymers at different concentrations effectively sustain drug release with prime permeation profiles and better bioavailability. Therefore, these formulated patches can be employed for the potential management of topical diseases, such as psoriasis. [ABSTRACT FROM AUTHOR]

BACKGROUND Recent studies demonstrate that fish byproducts can be used as sources of bioactive peptides for functional foods. Sturgeon skin contains abundant proteins but it has commonly been discarded during sturgeon processing. The objective of the present work was to identify and characterize the bioactive peptides from protein hydrolysates of sturgeon skin. RESULTS: Sturgeon skin protein extract (SKPE) hydrolyzed by flavourzyme for 60 min exhibited high antioxidant activity, dipeptidyl peptidase IV (DPP‐IV) and angiotensin converting enzyme (ACE) inhibitory activity. The sequences of peptides from flavourzyme hydrolysates were identified using high‐performance liquid chromatography–tandem mass spectrometry. Gly‐Asp‐Arg‐Gly‐Glu‐Ser‐Gly‐Pro‐Ala (P1) showed the highest DPPH radical scavenging activity (DPPH IC50 = 1.93 mmol L−1). Gly‐Pro‐Ala‐Gly‐Glu‐Arg‐Gly‐Glu‐Gly‐Gly‐Pro‐Arg (P11) (DPP‐IV IC50 = 2.14 mmol L−1) and Ser‐Pro‐Gly‐Pro‐Asp‐Gly‐Lys‐Thr‐Gly‐Pro‐Arg (P12) (DPP‐IV IC50 = 2.61 mmol L−1) exhibited the strongest DPP‐IV inhibitory activity. Gly‐Pro‐Pro‐Gly‐Ala‐Asp‐Gly‐Gln‐Ala‐Gly‐Ala‐Lys (P6) displayed the highest ACE inhibitory activity (ACE IC50 = 3.77 mmol L−1). The molecular docking analysis revealed that DPP‐IV inhibition of P11 and P12 are mainly attributed to hydrogen bonds and hydrophobic interactions, whereas ACE inhibition of P6 is mainly attributed to strong hydrogen bonds. CONCLUSIONS: These results indicate that SKPE hydrolysates generated by flavourzyme are potential sources of bioactive peptides that could be used in the health food industry. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here, we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa, and skin commensals. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to MRSA and P. aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection. [ABSTRACT FROM AUTHOR]

Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is broad and encompasses subepidermal conditions such as bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, and linear IgA bullous dermatosis, as well as intraepidermal conditions such as pemphigus and its variants. The pathophysiology of each condition is incompletely understood but broadly involves the formation of autoantibodies targeting skin adhesion proteins, a process that relies on a complex interplay between a dysregulated immune system, genetic predisposition, and environmental factors. We review the impact of nutrition on pathogenesis, clinical course, and treatment of various autoimmune bullous diseases. [ABSTRACT FROM AUTHOR]

Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target. [ABSTRACT FROM AUTHOR]

Summary: Background: The regulation of melanogenesis has been investigated as a long‐held aim for pharmaceutical manipulations with denotations for malignancy of melanoma. Mucins have a protective function in epithelial organs; however, in the most outer organ, the skin, the role of mucins has not been studied enough. Objectives: Our initial hypothesis developed from the identification of correlations between pigmentation and expressions of skin mucins, particularly those existing in skin tissue. We aimed to investigate the action of mucins in human melanocytic cells. Materials and methods: The expression of mucin proteins in human skin was investigated using microarray data from the Human Protein Atlas consortium (HPA) and the Genotype‐Tissue Expression consortium (GTEx) database. Mucin expression was measured at RNA and protein levels in melanoma cells. The findings were further validated and confirmed by analysis of independent experiments. Results: We found that the several mucin proteins showed expression in human skin cells and among these, mucin‐like protein 1 (MUCL1) showed the highest expression and also clear negative correlation with melanogenesis in epidermal melanocytes. We confirmed the correlations between melanogenesis and MUCL1 by revealing negative correlations in melanocytes with different melanin production, resulting from increased composition of threonine, mucin‐conforming amino acid, and increased autophagy‐related forkhead‐box O signalling. Furthermore, threonine itself affects melanogenesis and metastatic activity in melanoma cells. Conclusions: We identified a significant association between MUCL1 and threonine with melanogenesis and metastasis‐related genes in melanoma cells. Our results define a novel mechanism of mucin regulation, suggesting diagnostic and preventive roles of MUCL1 in cutaneous melanoma. Whatis already known about this topic? Despite considerable advances in radioactive therapeutics or chemotherapeutic approaches for the treatment of abnormal melanogenesis, there are still many caveats to delivery, effectiveness and safety, thus leaving a necessity for more immediate pharmaceutical targets.Mucins have protective and chemical barrier functions in epithelial organs; however, in the skin, mucin has scarce expression and is known only as a diagnostic aid in skin disorders such as mucinosis. Whatdoes this study add? We provide detailed analysis demonstrating the potential of mucin‐like protein 1 (MUCL1), which showed negative correlations in melanocytes with different melanin production, resulting from increased composition of threonine and increased autophagy‐related forkhead‐box O signalling in epidermal melanocytes and melanoma cells.We established that through an alternative pathway for MUCL1 biosynthesis, threonine supplementation recovers MUCL1 levels in melanoma. Changes, brought on by the essential amino acid threonine, resulted in substantial modulations in melanogenesis and reduced metastasis‐related genes. Whatis the translational message? This study demonstrates for the first time that the mucin protein of skin cells is compounded by distorted mucin homeostasis, with major effects on melanogenesis and metastasis‐related genes in melanoma.We anticipate that these novel findings will be of keen interest to the community of scientists and medical practitioners examining skin dysfunction. Linked Comment: C. Casalou and D.J. Tobin. Br J Dermatol 2022; 186:388–389. Plain language summary available online [ABSTRACT FROM AUTHOR]

Keywords: Flavobacterium psychrophilum; immersion challenge; immersion vaccination; proteomics; rainbow trout; skin mucus EN Flavobacterium psychrophilum immersion challenge immersion vaccination proteomics rainbow trout skin mucus 491 495 5 02/10/22 20220301 NES 220301 I Flavobacterium psychrophilum i is one of the most important pathogens affecting rainbow trout ( I Oncorhynchus mykiss i ) worldwide at the fry stage of their life cycle. Briefly, skin mucus was sampled by placing three fish (from each duplicate tank giving 2 pools of mucus/group) into a plastic bag containing 5 ml of Tris-buffered saline (TBS: 10 mM Tris base and 0.5 M NaCl, pH 7.5) and gently massaging for 2 min. In the current study, we examined the proteins of skin mucus of rainbow trout following immersion vaccination with I F. psychrophilum i . [Extracted from the article]

Background: Skin is continuously exposed to oxidative stress caused by reactive oxygen species (ROS) produced by the ultraviolet (UV) light, and it is important to evaluate the antioxidant activity. Carbonylated proteins (CPs) are candidate markers of oxidative modification as a result from the ROS. We aimed to develop the CP‐based method to assess the efficacy of antioxidants in human skin. Methods: Ten healthy females were enrolled in the study to determine the UVA dosage for CP production, and another 10 females were included to evaluate the antioxidative activity. The stratum corneum was collected from test skin using D‐Squame tape, and CPs from the SC were stained by fluorescence labeling and observed using a fluorescence microscope. Results: CP level significantly increased with UVA irradiation from 15J/cm2 to 50J/cm2 compared to the control (non‐UVA) area. CP production significantly increased by 34.38% and 35.22% in UVA irradiation and squalene (vehicle) areas. 5% α‐tocopherol and β‐carotene significantly increased the CP production by 20.77% and 19.34% after 2 hours of 30J of UVA irradiation compared to control area. Inhibition rate of CPs in 5% α‐tocopherol and 5% β‐carotene showed 41.45% and 45.37% after 2 hours of UVA irradiation. Conclusion: This study developed the simple, visual, and direct in vivo method to evaluate the antioxidative activity for products in human skin by measuring the CP level as an oxidative modification caused by UVA‐induced ROS generation. [ABSTRACT FROM AUTHOR]

Background: In the skin, hyaluronic acid is broken down to smaller fragments by hyaluronidase enzymes, particularly when skin is wounded. The impact of various molecular weight fragments of HA on normal human epidermal keratinocytes (NHEK) with regard to expression of important cellular proteins has not been deeply explored. Aims: Examination of three molecular weight (Mw) fractions of hyaluronic acid: 1) average Mw of the high fraction: 1.5–2 MDa, 2) average Mw of the medium fraction: 200–500 kDa, and 3) average Mw of the low fraction: 5–10 kDa and a unique 1:1:1 composite complex of the three HA fragments (Triluronic® Acid) was done to examine the influence of the HA on two critical skin cell protein targets: hyaluronan synthase‐1 (HAS‐1) and the HA binding protein cluster of differentiation 44 (CD44). Methods: NHEKs were treated in vitro with a 1.0% stock solution of each HA Mw fraction at 1.0, 0.5, and 0.1% concentrations of the 1.0% solution and the polysaccharide composite at the same concentrations for 48 Hrs. The cells were than analyzed by ELISA protein assays for HAS‐1 and CD44 protein content. Results: Examination of HAS‐1 protein expression indicates that none of the HA test materials influenced the expression of HAS‐1 at any concentration. Examination of the CD44 protein expression indicated that the low Mw fraction and the commercial complex of the three Mw fractions upregulated CD44 protein expression in NHEKs, but the medium Mw and high Mw HA fractions did not. Conclusions: In this work, it was demonstrated that HA can influence the expression of CD44 protein, a critical HA transmembrane HA binding protein, and the influence appears to be molecular weight dependent. [ABSTRACT FROM AUTHOR]

In order to explore the influence of inflammatory factors on human skin, inflammatory factor TNF-α was used as a stimulant to act on human skin cells. In this study, TNF-α was used as a stimulant to stimulate human skin cells. The results show that the content of senescence related secretion phenotype, IL-6 and IL-8, in the cells increases, and the cells are under the senescence state. The contents of type I collagen per protein in human skin fibroblasts, which are treated with 20, 100 and 200 ng/mL TNF-α for 24 h, are 2.740, 2.270 and 1.595 mg, respectively, lower than those in the control group; after 4 h of treatment, the contents of MMP-1 per protein are 3.10, 3.12 and 3.10 ng, respectively, higher than those in the control group. At the same time, compared with the control group, the content of intracellular reactive oxygen species is increased, and the balance of intracellular redox system is broken after the keratinocytes exposed to TNF-α. From the above experimental results, the inflammatory factor TNF-α causes the expression of collagen in skin cells abnormal, breaks the redox system, and has a certain effect on accelerating skin aging. Therefore, TNF-α can be used as a stimulant to establish a chronic inflammatory skin aging model. Follow-up experiments established a chronic inflammatory aging model through 200 ng/mL TNF-α, and investigated and compared the inhibitory effects of vitamin C, dragon's blood extract, and Dendrobium officinale extract on it. The results show that, compared with the control group, 0.1 mg/mL vitamin C, 0.06 mg/mL dragon's blood, and 0.5 mg/mL Dendrobium officinale extract can effectively promote the synthesis of intracellular collagen, and the contents per unit protein are 4.95, 4.84, 4.08 mg, respectively; can inhibit the expression of MMP-1, and its contents per unit protein are 1.31, 0.84, and 1.26 ng, respectively; can clear the content of reactive oxygen species in the cells and maintain the intracellular redox balance. The results show that vitamin C, as a recognized anti-aging substance, has the same anti-inflammatory aging effect; the extract of Resina draconis and Dendrobium officinale also have certain anti-inflammatory aging effect. [ABSTRACT FROM AUTHOR]

CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation. [ABSTRACT FROM AUTHOR]

Background: Novel skin-based tests for tuberculosis infection might present suitable alternatives to current tests; however, diagnostic performance of new tests compared with the purified protein derivative-tuberculin skin test (TST) or interferon-γ release assays (IGRA) needs systematic assessment.Methods: In this systematic review and meta-analysis, we searched English (Medline OVID), Chinese (Chinese Biomedical Literature Database and the China National Knowledge Infrastructure), and Russian (e-library) databases from the inception of each database to May 15, 2019, (with updated search of the Russian and English databases on Oct, 20 2020) using terms "ESAT6" OR "CFP10" AND "skin test" AND "Tuberculosis" OR "C-Tb" OR "Diaskintest". We included studies reporting on the performance of index tests alone or compared with a comparator. Inclusion criteria varied according to review objectives and performance outcome, but reporting of test cut-offs for positivity applied to study population was required from all studies. We used a hierarchy of reference standards for tuberculosis infection consistent with the 2020 WHO framework to evaluate diagnostic performance. Two authors independently reviewed the titles and abstracts for English and Chinese (LF and MK) and Russian studies (MK and VN). Study quality was assessed with QUADAS-2. Pooled random-effects estimates are presented when appropriate for total agreement proportion, sensitivity in microbiologically confirmed tuberculosis and specificity in cohorts with low risk of tuberculosis infection. This study is registered with PROSPERO, CRD42019135572.Findings: We identified 1466 original articles, of which 37 (2·5%) studies, including 10 915 individuals (7111 Diaskintest, 2744 C-Tb, 887 EC, 173 DPPD), were included in the qualitative analysis (29 [78%] studies of Diaskintest, five [15%] studies of C-Tb, two [5%] studies of EC-skintest, and one [3%] study of DPPD). 22 (1·5%) studies including 5810 individuals (3143 Diaskintest, 2129 C-Tb, 538 EC-skintest) were included in the quantitative analysis: 15 (68%) of Diaskintest, five (23%) of C-Tb, and two (9%) of EC-skintest. Tested sub-populations included individuals with HIV, children (0-18 years), and individuals exposed to tuberculosis. Studies were heterogeneous with moderate to high risk of bias. Nine head-to-head studies of index test versus TST and IGRA permitted direct comparisons and pooling. In a mixed cohort of people with and without tuberculosis, Diaskintest pooled agreement with IGRA was 87·16% (95% CI 79·47-92·24) and 55·45% (46·08-64·45) with TST-5 mm cut-off (TST5 mm). Diaskintest sensitivity was 91·18% (95% CI 81·72-95·98) compared with 88·24% (78·20-94·01) for TST5 mm, 89·66 (78·83-95·28) for IGRA QuantiFERON, and 90·91% (79·95-96·16) for TSPOT.TB. C-Tb agreement with IGRA in individuals with active tuberculosis was 79·80% (95% CI 76·10-83·07) compared with 78·92% (74·65-82·63) for TST5 mm/15 mm cut-off (TST5 mm/15 mm). TST5/15mm reflects threshold in cohorts that applied stratified cutoffs: 5 mm for HIV-infected, immunocompromised, or BCG-naive individuals, and 15mm for BCG-vaccinated immunocompetent individuals. C-Tb sensitivity was 74·52% (95% CI 70·39-78·25) compared with a sensitivity of 78·18% (67·75-85·94) for TST5 mm/15 mm, and 71·67% (63·44-78·68) for IGRA. Specificity was 97·85% (95% CI 93·96-99·25) for C-Tb versus 93·31% (90·22-95·48) for TST 15 mm cut-off and 99·15% (79·66-99·97) for IGRA. EC-skintest sensitivity was 86·06% (95% CI 82·39-89·07).Interpretation: Novel skin-based tests for tuberculosis infection appear to perform similarly to IGRA or TST; however, study quality varied. Evaluation of test performance, patient-important outcomes, and diagnostic use in current clinical algorithms will inform implementation in key populations.Funding: StopTB (New Diagnostics Working Group) and FIND.Translations: For the Chinese and Russian translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Buruli ulcer (BU) is a neglected tropical disease caused by subcutaneous infection with Mycobacterium ulcerans and its exotoxin mycolactone. BU displays coagulative necrosis and widespread fibrin deposition in affected skin tissues. Despite this, the role of the vasculature in BU pathogenesis remains almost completely unexplored. We hypothesise that fibrin-driven ischemia can be an 'indirect' route to mycolactone-dependent tissue necrosis by a mechanism involving vascular dysfunction. Here, we tracked >900 vessels within contiguous tissue sections from eight BU patient biopsies. Our aim was to evaluate their vascular and coagulation biomarker phenotype and explore potential links to fibrin deposition. We also integrated this with our understanding of mycolactone's mechanism of action at Sec61 and its impact on proteins involved in maintaining normal vascular function. Our findings showed that endothelial cell dysfunction is common in skin tissue adjacent to necrotic regions. There was little evidence of primary haemostasis, perhaps due to mycolactone-dependent depletion of endothelial von Willebrand factor. Instead, fibrin staining appeared to be linked to the extrinsic pathway activator, tissue factor (TF). There was significantly greater than expected fibrin staining around vessels that had TF staining within the stroma, and this correlated with the distance it extended from the vessel basement membrane. TF-induced fibrin deposition in these locations would require plasma proteins outside of vessels, therefore we investigated whether mycolactone could increase vascular permeability in vitro. This was indeed the case, and leakage was further exacerbated by IL-1β. Mycolactone caused the loss of endothelial adherens and tight junctions by the depletion of VE-cadherin, TIE-1, TIE-2 and JAM-C; all Sec61-dependent proteins. Taken together, our findings suggest that both vascular and lymphatic vessels in BU lesions become "leaky" during infection, due to the unique action of mycolactone, allowing TF-containing structures and plasma proteins into skin tissue, ultimately leading to local coagulopathy and tissue ischemia. Author summary: To date, the debilitating skin disease Buruli ulcer remains a public health concern and financial burden in low or middle-income countries, especially in tropical regions. Late diagnosis is frequent in remote areas, perhaps due to the painlessness of the disease. Hence patients often present with large, destructive opened ulcers leading to delayed wound closure or even lifelong disability. The infectious agent produces a toxin called mycolactone that drives the disease. We previously found evidence that the vascular system is disrupted by mycolactone in these lesions, and now we have further explored potential explanations for these findings by looking at the expression of vascular markers in BU. In a detailed analysis of patient skin punch biopsies, we identified distinct expression patterns of certain proteins and found that tissue factor, which initiates the so-called extrinsic pathway of blood clotting, is particularly important. Mycolactone is able to disrupt the barrier function of the endothelium, further aggravating the diseased phenotype, which may explain how clotting factors access the tissue. Altogether, such localised hypercoagulation in Buruli ulcer skin lesions may contribute to the development of the lesion. [ABSTRACT FROM AUTHOR]

Fleece rot develops following prolonged wetting of sheep when bacterial proliferation in wool and on skin induces exudation of serum proteins onto the skin surface and causes damage to wool follicles and fibres. These processes create an attractive environment for blowflies to lay eggs, leading to body strike. Current reliance on insecticides for prevention and treatment of fly strike is being increasingly challenged by development of insecticide resistance. This review examines the large body of past research on the bacterial causes of fleece rot, the genetics of sheep susceptibility and resistance, the characteristics of the resulting immune defence reactions, and attempts to control fleece rot by vaccination. The high dependence on weather conditions for expression of fleece rot hampers studies on the disease. Normal skin and wool are populated by a dynamic microbial community. During adverse environmental conditions, natural resistance to fleece rot associated with physical characteristics of wool and skin can be overwhelmed and a complex mix of bacteria flourishes. Prolonged hydration alone, and in combination with bacterial exoproducts, induces dermatitis and exudation of immunoglobulins and other serum proteins onto the skin surface. Pathogens do not usually penetrate the epidermis. Nonetheless, during prolonged skin hydration, sheep can become sensitised to fleece rot pathogens and produce antibodies. Antibody titres rise late within a typical (3 week) case of fleece rot. High naturally acquired antibody titres may contribute to resistance to fleece rot. In contrast to some evidence for a protective role of antibody, there is little evidence for innate or adaptive cellular immune responses contributing to protection against fleece rot pathogens. Previous attempts to develop vaccines have met with mixed success. Nonetheless, there remain prospects for development of a new vaccine to control fleece rot. Further knowledge on the microbial ecology of normal and wet skin would assist this endeavour and may help identify other control strategies. Following wetting for several days or more, bacteria proliferate on the skin and in the wool to cause fleece rot which predisposes sheep to fly strike. This review examines the bacteria associated with fleece rot, their role in the disease, sheep factors influencing susceptibility to infection, defences of the sheep against infection and past efforts to develop vaccines. This background sets the scene for an accompanying review on new opportunities for vaccine development. [ABSTRACT FROM AUTHOR]

Skin ageing is a cumulative result of oxidative stress, predominantly caused by reactive oxygen species (ROS). Respiration, pollutants, toxins, or ultraviolet A (UVA) irradiation produce ROS with 80% of skin damage attributed to UVA irradiation. Anti-ageing peptides and proteins are considered valuable compounds for removing ROS to prevent skin ageing and maintenance of skin health. In this review, skin ageing theory has been illustrated with a focus on the mechanism and relationship with anti-ageing peptides and proteins. The effects, classification, and transport pathways of anti-ageing peptides and proteins across skin are summarized and discussed. Over the last decade, several novel formulations and advanced strategies have been developed to overcome the challenges in the dermal delivery of proteins and peptides for skin ageing. This article also provides an in-depth review of the latest advancements in the dermal delivery of anti-ageing proteins and peptides. Based on these studies, this review prospected several semi-solid dosage forms to achieve topical applicability for anti-ageing peptides and proteins. [ABSTRACT FROM AUTHOR]

This article introduces the ICADA 2023 review articles on the pathogenesis of canine atopic dermatitis (cAD) and provides an updated definition of cAD. The review articles cover various topics related to cAD, including genetic and environmental factors, skin barrier abnormalities, the cutaneous microbiome, and cytokines and chemokines. The updated definition of cAD highlights the multifactorial nature of the disease and emphasizes the need for multimodal management. The articles aim to summarize the most important studies on cAD since 2015 and contribute to a better understanding of the complexity of the condition. [Extracted from the article]